ID STING_MOUSE Reviewed; 378 AA. AC Q3TBT3; A7YGY9; Q3TAV5; Q3TYP5; Q3TZY8; Q3UJW3; Q8C227; Q8C5Q3; Q8K393; AC Q9CZY7; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 144. DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:19776740}; DE Short=mSTING {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:19776740, ECO:0000303|PubMed:25636800}; 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}; DE Short=MMITA {ECO:0000303|PubMed:18818105}; DE AltName: Full=Transmembrane protein 173; GN Name=Sting1 {ECO:0000312|MGI:MGI:1919762}; GN Synonyms=Eris {ECO:0000303|PubMed:19433799}, Mita GN {ECO:0000303|PubMed:18818105}, Mpys {ECO:0000303|PubMed:18559423}, GN Sting {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:26669264}, GN Tmem173 {ECO:0000312|MGI:MGI:1919762}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. 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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, RP SUBUNIT, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION. RX PubMed=18559423; DOI=10.1128/mcb.00640-08; RA Jin L., Waterman P.M., Jonscher K.R., Short C.M., Reisdorph N.A., RA Cambier J.C.; RT "MPYS, a novel membrane tetraspanner, is associated with major RT histocompatibility complex class II and mediates transduction of apoptotic RT signals."; RL Mol. Cell. Biol. 28:5014-5026(2008). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC STRAIN=C57BL/6J; TISSUE=Embryo, Inner ear, Spleen, and Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary gland; 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 [6] RP FUNCTION. 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 [7] RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE. 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 FUNCTION. 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [10] 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 [11] 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 [12] RP FUNCTION, CGAMP-BINDING, AND MUTAGENESIS OF SER-161; TYR-239 AND ASN-241. 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 [13] RP FUNCTION. 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 [14] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ILE-229. 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 [15] RP FUNCTION, DOMAIN, INTERACTION WITH IRF3, PHOSPHORYLATION AT SER-357 AND RP SER-365, AND MUTAGENESIS OF SER-357 AND SER-365. 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 [16] 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 [17] RP SUMOYLATION AT LYS-337, PHOSPHORYLATION AT SER-365, SUBCELLULAR LOCATION, RP DESUMOYLATION, AND MUTAGENESIS OF 326-GLN-GLU-327 AND LYS-337. RX PubMed=27637147; DOI=10.1016/j.immuni.2016.08.014; RA Hu M.M., Yang Q., Xie X.Q., Liao C.Y., Lin H., Liu T.T., Yin L., Shu H.B.; RT "Sumoylation promotes the stability of the DNA sensor cGAS and the adaptor RT STING to regulate the kinetics of response to DNA virus."; RL Immunity 45:555-569(2016). RN [18] RP PALMITOYLATION AT CYS-88 AND CYS-91, FUNCTION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 64-CYS-CYS-65; 88-CYS--CYS-91; CYS-147; CYS-205; CYS-256; RP CYS-291 AND CYS-308. RX PubMed=27324217; DOI=10.1038/ncomms11932; RA Mukai K., Konno H., Akiba T., Uemura T., Waguri S., Kobayashi T., RA Barber G.N., Arai H., Taguchi T.; RT "Activation of STING requires palmitoylation at the Golgi."; RL Nat. Commun. 7:11932-11932(2016). RN [19] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=29056340; DOI=10.1016/j.cell.2017.09.034; RA Moretti J., Roy S., Bozec D., Martinez J., Chapman J.R., Ueberheide B., RA Lamming D.W., Chen Z.J., Horng T., Yeretssian G., Green D.R., Blander J.M.; RT "STING senses microbial viability to orchestrate stress-mediated autophagy RT of the endoplasmic reticulum."; RL Cell 171:809-823(2017). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=28930687; DOI=10.1016/j.celrep.2017.08.085; RA Takahama M., Fukuda M., Ohbayashi N., Kozaki T., Misawa T., Okamoto T., RA Matsuura Y., Akira S., Saitoh T.; RT "The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune RT Responses."; RL Cell Rep. 20:2944-2954(2017). RN [21] RP FUNCTION, AND INTERACTION WITH IFI204. RX PubMed=28529930; DOI=10.3389/fcimb.2017.00169; RA Chunfa L., Xin S., Qiang L., Sreevatsan S., Yang L., Zhao D., Zhou X.; RT "The Central Role of IFI204 in IFN-beta Release and Autophagy Activation RT during Mycobacterium bovis Infection."; RL Front. Cell. Infect. Microbiol. 7:169-169(2017). RN [22] RP FUNCTION, ACTIVITY REGULATION, PALMITOYLATION, AND MUTAGENESIS OF 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 [23] 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 [24] RP SUBCELLULAR LOCATION, UBIQUITINATION, AND INTERACTION WITH SQSTM1. RX PubMed=29496741; DOI=10.15252/embj.201797858; RA Prabakaran T., Bodda C., Krapp C., Zhang B.C., Christensen M.H., Sun C., RA Reinert L., Cai Y., Jensen S.B., Skouboe M.K., Nyengaard J.R., RA Thompson C.B., Lebbink R.J., Sen G.C., van Loo G., Nielsen R., Komatsu M., RA Nejsum L.N., Jakobsen M.R., Gyrd-Hansen M., Paludan S.R.; RT "Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent RT autophagy pathway activated by TBK1."; RL EMBO J. 37:0-0(2018). RN [25] RP FUNCTION, INTERACTION WITH TMEM203, AND SUBCELLULAR LOCATION. RX PubMed=31346090; DOI=10.1073/pnas.1901090116; RA Li Y., James S.J., Wyllie D.H., Wynne C., Czibula A., Bukhari A., Pye K., RA Bte Mustafah S.M., Fajka-Boja R., Szabo E., Angyal A., Hegedus Z., RA Kovacs L., Hill A.V.S., Jefferies C.A., Wilson H.L., Yongliang Z., RA Kiss-Toth E.; RT "TMEM203 is a binding partner and regulator of STING-mediated inflammatory RT signaling in macrophages."; RL Proc. Natl. Acad. Sci. U.S.A. 116:16479-16488(2019). RN [26] 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 [27] RP INTERACTION WITH TAB1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT RP SER-354. 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 [28] {ECO:0007744|PDB:4KBY, ECO:0007744|PDB:4KC0} RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 138-344 IN COMPLEX WITH CYCLIC RP DIGUANOSINE MONOPHOSPHATE, FUNCTION, AND SUBUNIT. RX PubMed=23519410; DOI=10.1107/s0907444912047269; RA Chin K.H., Tu Z.L., Su Y.C., Yu Y.J., Chen H.C., Lo Y.C., Chen C.P., RA Barber G.N., Chuah M.L., Liang Z.X., Chou S.H.; RT "Novel c-di-GMP recognition modes of the mouse innate immune adaptor RT protein STING."; RL Acta Crystallogr. D 69:352-366(2013). RN [29] {ECO:0007744|PDB:4LOJ, ECO:0007744|PDB:4LOK, ECO:0007744|PDB:4LOL} RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 154-340 IN COMPLEX WITH RP 2'3'-CGAMP; 3'3'-CGAMP AND DMXAA, FUNCTION, AND ACTIVITY REGULATION. 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). 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:18818105, CC PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264, CC PubMed:27324217, PubMed:28529930, PubMed:29973723, PubMed:31346090). CC Innate immune response is triggered in response to non-CpG double- CC stranded DNA from viruses and bacteria delivered to the cytoplasm CC (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, CC PubMed:26669264). Acts by binding cyclic dinucleotides: recognizes and CC binds cyclic di-GMP (c-di-GMP), a second messenger produced by CC bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a CC messenger produced by CGAS in response to DNA virus in the cytosol CC (PubMed:21947006, PubMed:23722158, PubMed:23258412, PubMed:23519410, CC PubMed:23910378). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 CC oligomerizes, translocates from the endoplasmic reticulum and is CC phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and CC subsequent activation of the transcription factor IRF3 to induce CC expression of type I interferon and exert a potent anti-viral state CC (PubMed:25636800, PubMed:27324217, PubMed:29973723). Exhibits 2',3' CC phosphodiester linkage-specific ligand recognition: can bind both 2'-3' CC linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially CC activated by 2'-3' linked cGAMP (PubMed:26300263). The preference for CC 2'-3'-cGAMP, compared to other linkage isomers is probably due to the CC ligand itself, whichs adopts an organized free-ligand conformation that CC resembles the STING1-bound conformation and pays low energy costs in CC changing into the active conformation (By similarity). In addition to CC promote the production of type I interferons, plays a direct role in CC autophagy (PubMed:30568238). Following cGAMP-binding, STING1 buds from CC the endoplasmic reticulum into COPII vesicles, which then form the CC endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By CC similarity). 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 (By similarity). Promotes autophagy by acting as a proton CC channel that directs proton efflux from the Golgi to facilitate CC MAP1LC3B/LC3B lipidation (By similarity). The autophagy- and CC interferon-inducing activities can be uncoupled and autophagy induction CC is independent of TBK1 phosphorylation (By similarity). Autophagy is CC also triggered upon infection by bacteria: following c-di-GMP-binding, CC which is produced by live Gram-positive bacteria, promotes CC reticulophagy (PubMed:29056340). May be involved in translocon CC function, the translocon possibly being able to influence the induction CC of type I interferons (By similarity). May be involved in transduction CC of apoptotic signals via its association with the major CC histocompatibility complex class II (MHC-II) (PubMed:18559423). CC {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:18559423, CC ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, CC ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, CC ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23519410, CC ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23910378, CC ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26229117, CC ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:26669264, CC ECO:0000269|PubMed:27324217, ECO:0000269|PubMed:28529930, CC ECO:0000269|PubMed:29056340, ECO:0000269|PubMed:29973723, CC ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:31346090}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; CC Evidence={ECO:0000250|UniProtKB:Q86WV6}; CC -!- ACTIVITY REGULATION: Activated by anticancer drug 5,6- CC dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:23910378, CC PubMed:26669264). Specifically inhibited by nitrofuran derivatives C- CC 178 and C-176, which covalently bind Cys-91 and prevent palmitoylation CC and subsequent activation od STING1 (PubMed:29973723). CC {ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:26669264, CC ECO:0000269|PubMed:29973723}. 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:18559423). Homotetramer; in CC presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and CC higher-order oligomers through side-by-side packing (By similarity). CC Interacts (when phosphorylated) with IRF3; following activation and CC phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By CC similarity). Interacts with RIGI, MAVS and SSR2 (By similarity). CC Interacts with RNF5 and TRIM56 (By similarity). Interacts with TBK1; CC when homodimer, leading to subsequent production of IFN-beta (By CC similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts CC with TRIM29; this interaction induces STING1 ubiquitination and CC subsequent degradation (By similarity). Associates with the MHC-II CC complex (PubMed:18559423). Interacts with STEEP1; interaction takes CC place upon cGAMP-activation and STING1 phosphorylation by MAP3K7/TAK1 CC and promotes STING1 translocation to COPII vesicles (By similarity). CC Interacts with SEC24A, SEC24B and SEC24C; promoting translocation to CC COPII vesicles (By similarity). Interacts (when ubiquitinated) with CC SQSTM1; leading to relocalization to autophagosomes (PubMed:29496741). CC Interacts with SURF4 (By similarity). Interacts with HNRNPA2B1 CC (PubMed:31320558). Interacts with ZDHHC1; ZDHHC1 constitutively CC interacts with STING1 and in presence of DNA viruses activates it by CC promoting its cGAMP-induced oligomerization and the recruitment of CC downstream signaling components (By similarity). Interacts with CC ZDHHC11; in presence of DNA viruses promotes the recruitment of IRF3 to CC STING1 (By similarity). Interacts with TOMM70 (By similarity). CC Interacts with IFI204 (PubMed:28529930). Interacts with TAB1; promoting CC recruitment of TAB1 to the endoplasmic reticulum membrane and CC subsequent activation of MAP3K7/TAK1 (PubMed:37832545). Interacts (via CC transmembrane domain) with TMEM203 (PubMed:31346090). CC {ECO:0000250|UniProtKB:E1C7U0, ECO:0000250|UniProtKB:Q86WV6, CC ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:28529930, CC ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:31320558, CC ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:37832545}. CC -!- INTERACTION: CC Q3TBT3; Q91VN6: Ddx41; NbExp=4; IntAct=EBI-3862093, EBI-2551902; CC Q3TBT3; Q9WUN2: Tbk1; NbExp=3; IntAct=EBI-3862093, EBI-764193; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:27324217, CC ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:37832545}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:Q86WV6}. Endoplasmic reticulum-Golgi CC intermediate compartment membrane {ECO:0000269|PubMed:28930687, CC ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:37832545}; Multi-pass CC membrane protein {ECO:0000255}. Golgi apparatus membrane CC {ECO:0000269|PubMed:27324217, ECO:0000269|PubMed:29973723}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome CC membrane {ECO:0000269|PubMed:29056340, ECO:0000269|PubMed:29496741}; CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:18559423}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:18559423}; Multi-pass CC membrane protein {ECO:0000255}. Lysosome membrane CC {ECO:0000269|PubMed:31346090}; 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. 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 (By similarity). CC Localizes in the lysosome membrane in a TMEM203-dependent manner CC (PubMed:31346090). {ECO:0000250|UniProtKB:Q86WV6, CC ECO:0000269|PubMed:31346090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q3TBT3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q3TBT3-2; Sequence=VSP_022284; CC Name=3; CC IsoId=Q3TBT3-3; Sequence=VSP_022285; CC -!- TISSUE SPECIFICITY: Present in spleen and thymus tissue. Also present CC in dendritic cells (at protein level). {ECO:0000269|PubMed:18559423}. CC -!- DEVELOPMENTAL STAGE: Expressed throughout the B-cell lineage prior to CC the plasma cell stage but occurs at highest levels in mature B-cells. CC Highly expressed in cells representing mature stages of B-cells but CC weakly expressed in pre-B cells, immature B-cells, and memory B-cell CC stages. Not detected in plasma cells. {ECO:0000269|PubMed:18559423}. 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 (By similarity). 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 (By CC similarity). {ECO:0000250|UniProtKB:E1C7U0, CC ECO:0000250|UniProtKB:Q86WV6}. CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following CC phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 CC recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to CC induce type-I interferons and other cytokines. CC {ECO:0000250|UniProtKB:Q86WV6}. CC -!- DOMAIN: The N-terminal domain interacts with glycerophospholipids and CC phospholipids. {ECO:0000250|UniProtKB:Q86WV6}. CC -!- PTM: Phosphorylation by TBK1 leads to activation and production of IFN- CC beta (By similarity). Following cyclic nucleotide (c-di-GMP or cGAMP)- CC binding, activation and translocation from the endoplasmic reticulum, CC STING1 is phosphorylated by TBK1 at Ser-365 in the pLxIS motif (By CC similarity). The phosphorylated pLxIS motif constitutes an IRF3-binding CC motif, leading to recruitment of the transcription factor IRF3 to CC induce type-I interferons and other cytokines (PubMed:27637147). The CC phosphorylated pLxIS motif facilitates SENP2 recruitment during late CC phase of viral infection (PubMed:27637147). Phosphorylated on tyrosine CC residues upon MHC-II aggregation (PubMed:18559423). Dephosphorylation CC by PPP6C leads to inactivation and decreased production of IFN-beta (By CC similarity). Phosphorylation at Ser-357 is also required to activate CC IRF3 (PubMed:25636800). Phosphorylation at Ser-354 by MAP3K7/TAK1 CC facilitates its interaction with STEEP1, promoting STING1 translocation CC to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q86WV6, CC ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:25636800, CC ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:37832545}. CC -!- PTM: Ubiquitinated (PubMed:29496741). Ubiquitinated via 'Lys-63'-linked CC ubiquitin chains in response to double-stranded DNA treatment, leading CC to relocalization to autophagosomes and subsequent degradation; this CC process is dependent on SQSTM1 (PubMed:29496741). 'Lys-63'-linked CC ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization CC and recruitment of the antiviral kinase TBK1 and subsequent production CC of IFN-beta (By similarity). 'Lys-48'-linked polyubiquitination at Lys- CC 150 occurring after viral infection is mediated by RNF5 and leads to CC proteasomal degradation (By similarity). '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 (By similarity). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated by CC USP20; leading to its stabilization and promotion of innate antiviral CC response (By similarity). 'Lys-48'-linked deubiquitinated by USP44; CC leading to its stabilization and promotion of innate antiviral response CC (By similarity). Deubiquitinated by USP13; leading to inhibition of CC innate antiviral response (By similarity). CC {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:29496741}. CC -!- PTM: Sumoylated at Lys-337 by TRIM38 during the early phase of viral CC infection, promoting its stability by preventing its relocalization to CC autophagosomes and subsequent degradation (PubMed:27637147). CC Desumoylated by SENP2 during the late phase of viral infection CC (PubMed:27637147). {ECO:0000269|PubMed:27637147}. CC -!- PTM: Palmitoylation takes place in the Golgi apparatus and creates a CC platform for the recruitment of TBK1. {ECO:0000269|PubMed:29973723}. CC -!- DISRUPTION PHENOTYPE: Defects in innate immunity. Death within 7 days CC of herpes simplex virus 1 (HSV-1) infection. In addition, mice show a CC remarkable reduction in cytotoxic T-cell responses after plasmid DNA CC vaccination. Cells fail to induce type I interferon production in CC response to dsDNA and infection with herpes simplex virus 1 (HSV-1) and CC L.monocytogenes that deliver DNA to the host cytosol. CC {ECO:0000269|PubMed:19776740}. CC -!- MISCELLANEOUS: Was named MPYS because the protein sequence begins by CC Met-Pro-Tyr-Ser residues. {ECO:0000303|PubMed:18559423}. CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH27757.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC37010.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAE42563.1; Type=Frameshift; Evidence={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; FJ222242; ACI46649.1; -; mRNA. DR EMBL; DQ910493; ABI78935.1; -; mRNA. DR EMBL; AK012006; BAB27972.1; -; mRNA. DR EMBL; AK077788; BAC37010.1; ALT_SEQ; mRNA. DR EMBL; AK089405; BAC40870.1; -; mRNA. DR EMBL; AK146284; BAE27042.1; -; mRNA. DR EMBL; AK153868; BAE32222.1; -; mRNA. DR EMBL; AK157370; BAE34068.1; -; mRNA. DR EMBL; AK158458; BAE34517.1; -; mRNA. DR EMBL; AK170724; BAE41981.1; -; mRNA. DR EMBL; AK171065; BAE42224.1; -; mRNA. DR EMBL; AK171203; BAE42310.1; -; mRNA. DR EMBL; AK171612; BAE42563.1; ALT_FRAME; mRNA. DR EMBL; CH466557; EDK97142.1; -; Genomic_DNA. DR EMBL; BC027757; AAH27757.1; ALT_INIT; mRNA. DR EMBL; BC046640; AAH46640.1; -; mRNA. DR CCDS; CCDS50253.1; -. [Q3TBT3-1] DR CCDS; CCDS89220.1; -. [Q3TBT3-3] DR RefSeq; NP_001276520.1; NM_001289591.1. [Q3TBT3-2] DR RefSeq; NP_001276521.1; NM_001289592.1. [Q3TBT3-3] DR RefSeq; NP_082537.1; NM_028261.1. [Q3TBT3-1] DR PDB; 4JC5; X-ray; 2.75 A; A/B=149-348. DR PDB; 4KBY; X-ray; 2.36 A; A/B=138-344. DR PDB; 4KC0; X-ray; 2.20 A; A/B=138-344. DR PDB; 4LOJ; X-ray; 1.77 A; A/B=154-340. DR PDB; 4LOK; X-ray; 2.07 A; A/B=154-340. DR PDB; 4LOL; X-ray; 2.43 A; A/B=154-340. DR PDB; 4YP1; X-ray; 2.65 A; A/B=138-344. DR PDB; 6XNN; X-ray; 2.49 A; A/B=154-340. DR PDBsum; 4JC5; -. DR PDBsum; 4KBY; -. DR PDBsum; 4KC0; -. DR PDBsum; 4LOJ; -. DR PDBsum; 4LOK; -. DR PDBsum; 4LOL; -. DR PDBsum; 4YP1; -. DR PDBsum; 6XNN; -. DR AlphaFoldDB; Q3TBT3; -. DR SMR; Q3TBT3; -. DR BioGRID; 215410; 1770. DR ComplexPortal; CPX-2128; Sting complex. DR DIP; DIP-59959N; -. DR IntAct; Q3TBT3; 105. DR STRING; 10090.ENSMUSP00000111393; -. DR BindingDB; Q3TBT3; -. DR ChEMBL; CHEMBL4523311; -. DR GuidetoPHARMACOLOGY; 2902; -. DR iPTMnet; Q3TBT3; -. DR PhosphoSitePlus; Q3TBT3; -. DR SwissPalm; Q3TBT3; -. DR EPD; Q3TBT3; -. DR MaxQB; Q3TBT3; -. DR PaxDb; 10090-ENSMUSP00000111393; -. DR PeptideAtlas; Q3TBT3; -. DR ProteomicsDB; 258752; -. [Q3TBT3-1] DR ProteomicsDB; 258753; -. [Q3TBT3-2] DR ProteomicsDB; 258754; -. [Q3TBT3-3] DR Pumba; Q3TBT3; -. DR Antibodypedia; 26796; 917 antibodies from 42 providers. DR Ensembl; ENSMUST00000115728.5; ENSMUSP00000111393.4; ENSMUSG00000024349.11. [Q3TBT3-1] DR Ensembl; ENSMUST00000235495.2; ENSMUSP00000157789.2; ENSMUSG00000024349.11. [Q3TBT3-3] DR Ensembl; ENSMUST00000237919.2; ENSMUSP00000157408.2; ENSMUSG00000024349.11. [Q3TBT3-1] DR GeneID; 72512; -. DR KEGG; mmu:72512; -. DR UCSC; uc008emt.3; mouse. [Q3TBT3-1] DR UCSC; uc008emu.3; mouse. [Q3TBT3-3] DR UCSC; uc008emv.3; mouse. [Q3TBT3-2] DR AGR; MGI:1919762; -. DR CTD; 340061; -. DR MGI; MGI:1919762; Sting1. DR VEuPathDB; HostDB:ENSMUSG00000024349; -. DR eggNOG; ENOG502R15M; Eukaryota. DR GeneTree; ENSGT00390000008582; -. DR HOGENOM; CLU_062449_0_0_1; -. DR InParanoid; Q3TBT3; -. DR OMA; QYGQAGF; -. DR OrthoDB; 5352585at2759; -. DR PhylomeDB; Q3TBT3; -. DR TreeFam; TF324444; -. DR Reactome; R-MMU-1834941; STING mediated induction of host immune responses. DR Reactome; R-MMU-3134975; Regulation of innate immune responses to cytosolic DNA. DR Reactome; R-MMU-3249367; STAT6-mediated induction of chemokines. DR Reactome; R-MMU-3270619; IRF3-mediated induction of type I IFN. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR BioGRID-ORCS; 72512; 1 hit in 80 CRISPR screens. DR ChiTaRS; Tmem173; mouse. DR PRO; PR:Q3TBT3; -. DR Proteomes; UP000000589; Chromosome 18. DR RNAct; Q3TBT3; Protein. DR Bgee; ENSMUSG00000024349; Expressed in lumbar dorsal root ganglion and 172 other cell types or tissues. DR ExpressionAtlas; Q3TBT3; baseline and differential. DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI. 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; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005777; C:peroxisome; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. 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; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0015252; F:proton channel activity; ISS:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0035591; F:signaling adaptor activity; ISS:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0002218; P:activation of innate immune response; IDA:ComplexPortal. DR GO; GO:0140374; P:antiviral innate immune response; ISO:MGI. DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB. DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISO:MGI. DR GO; GO:0035458; P:cellular response to interferon-beta; IMP:MGI. 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; ISO:MGI. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0045087; P:innate immune response; IDA:ComplexPortal. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISO:MGI. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. 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; ISO:MGI. DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI. DR GO; GO:0050727; P:regulation of inflammatory response; IGI:MGI. DR GO; GO:0061709; P:reticulophagy; IDA:UniProtKB. DR CDD; cd22658; STING_C_metazoan-like; 1. 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; Q3TBT3; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Cell membrane; Cytoplasm; KW Cytoplasmic vesicle; Endoplasmic reticulum; Golgi apparatus; Immunity; KW Innate immunity; Ion channel; Ion transport; Isopeptide bond; Lipoprotein; KW Lysosome; Membrane; Mitochondrion; Mitochondrion outer membrane; KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1..378 FT /note="Stimulator of interferon genes protein" FT /id="PRO_0000271117" FT TOPO_DOM 1..17 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TRANSMEM 18..34 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TOPO_DOM 35..44 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TRANSMEM 45..69 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TOPO_DOM 70..91 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TRANSMEM 92..106 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TOPO_DOM 107..115 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TRANSMEM 116..133 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT TOPO_DOM 134..378 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT REGION 1..189 FT /note="Mediates interaction with ZDHHC1 and ZDHHC11" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT REGION 152..339 FT /note="Cyclic dinucleotide-binding domain (CBD)" FT /evidence="ECO:0000269|PubMed:23519410" FT REGION 339..378 FT /note="C-terminal tail (CTT)" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT MOTIF 362..365 FT /note="pLxIS motif" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT BINDING 165 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:23519410, FT ECO:0007744|PDB:4KBY" FT BINDING 166 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT BINDING 166 FT /ligand="3',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:71501" FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0007744|PDB:4LOK" FT BINDING 237..240 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:23519410, FT ECO:0007744|PDB:4KBY" FT BINDING 237 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0007744|PDB:4LOJ" FT BINDING 237 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT BINDING 237 FT /ligand="3',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:71501" FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0007744|PDB:4LOK" FT BINDING 262 FT /ligand="2',3'-cGAMP" FT /ligand_id="ChEBI:CHEBI:143093" FT /evidence="ECO:0000269|PubMed:23910378, FT ECO:0007744|PDB:4LOJ" FT BINDING 262 FT /ligand="2',3'-cUAMP" FT /ligand_id="ChEBI:CHEBI:228269" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT BINDING 262 FT /ligand="3',3'-c-di-GMP" FT /ligand_id="ChEBI:CHEBI:58805" FT /evidence="ECO:0000269|PubMed:23519410, FT ECO:0007744|PDB:4KBY" FT MOD_RES 240 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT MOD_RES 354 FT /note="Phosphoserine; by MAP3K7" FT /evidence="ECO:0000269|PubMed:37832545" FT MOD_RES 357 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000305|PubMed:25636800" FT MOD_RES 365 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:25636800, FT ECO:0000269|PubMed:27637147" FT LIPID 88 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:27324217" FT LIPID 91 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:27324217" FT CROSSLNK 150 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT CROSSLNK 235 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q86WV6" FT CROSSLNK 337 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:27637147" FT VAR_SEQ 1 FT /note="M -> MIVESFGASGNPVGPCHFWSLYGVLLGVHWSVLHLGTFRGIRSAGLW FT LLM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_022284" FT VAR_SEQ 76..116 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_022285" FT MUTAGEN 64..65 FT /note="CC->SS: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 88..91 FT /note="CLGC->SLGS: Abolished palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 91 FT /note="C->A,S: Abolished inhibition by nitrofuran FT derivatives C-178 and C-176; abolished palmitoylation." FT /evidence="ECO:0000269|PubMed:29973723" FT MUTAGEN 147 FT /note="C->S: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 161 FT /note="S->A: Decrease in cGAMP-binding." FT /evidence="ECO:0000269|PubMed:23258412" FT MUTAGEN 205 FT /note="C->S: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 229 FT /note="I->A,G,T: Strongly decreases affinity for the FT synthetic compound 5,6-dimethylxanthenone 4-acetic acid FT (DMXAA)." FT /evidence="ECO:0000269|PubMed:26669264" FT MUTAGEN 239 FT /note="Y->S: Strong decrease in cGAMP-binding." FT /evidence="ECO:0000269|PubMed:23258412" FT MUTAGEN 241 FT /note="N->A: Strong decrease in cGAMP-binding." FT /evidence="ECO:0000269|PubMed:23258412" FT MUTAGEN 256 FT /note="C->S: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 291 FT /note="C->S: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 308 FT /note="C->S: Does not affect palmitoylation." FT /evidence="ECO:0000269|PubMed:27324217" FT MUTAGEN 326..327 FT /note="QE->AA: Decreased relocalization to autophagosomes FT and subsequent degradation." FT /evidence="ECO:0000269|PubMed:27637147" FT MUTAGEN 337 FT /note="K->R: Abolished sumoylation by TRIM38, leading to FT decreased stability." FT /evidence="ECO:0000269|PubMed:27637147" FT MUTAGEN 357 FT /note="S->A: Induces a decrease in phosphorylation by TBK1, FT leading to reduced ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:25636800" FT MUTAGEN 365 FT /note="S->A: Abolished ability to activate IRF3." FT /evidence="ECO:0000269|PubMed:25636800" FT CONFLICT 11 FT /note="P -> Q (in Ref. 3; BAE27042)" FT /evidence="ECO:0000305" FT CONFLICT 39 FT /note="P -> S (in Ref. 3; BAB27972)" FT /evidence="ECO:0000305" FT CONFLICT 98 FT /note="M -> V (in Ref. 3; BAE42563)" FT /evidence="ECO:0000305" FT CONFLICT 111 FT /note="T -> N (in Ref. 3; BAC37010)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="N -> D (in Ref. 3; FT BAE34068/BAE42310/BAE42224/BAE32222/BAE34517)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="E -> K (in Ref. 3; BAC37010)" FT /evidence="ECO:0000305" FT HELIX 156..164 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 167..170 FT /evidence="ECO:0007829|PDB:4LOJ" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:4LOK" FT HELIX 174..184 FT /evidence="ECO:0007829|PDB:4LOJ" FT TURN 185..189 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 195..202 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 211..213 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 218..223 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 227..231 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 234..239 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 242..248 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 251..260 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 262..272 FT /evidence="ECO:0007829|PDB:4LOJ" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 280..298 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 304..307 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 308..313 FT /evidence="ECO:0007829|PDB:4LOJ" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:4LOJ" FT HELIX 324..333 FT /evidence="ECO:0007829|PDB:4LOJ" SQ SEQUENCE 378 AA; 42830 MW; 656ED19097ACE4C8 CRC64; MPYSNLHPAI PRPRGHRSKY VALIFLVASL MILWVAKDPP NHTLKYLALH LASHELGLLL KNLCCLAEEL CHVQSRYQGS YWKAVRACLG CPIHCMAMIL LSSYFYFLQN TADIYLSWMF GLLVLYKSLS MLLGLQSLTP AEVSAVCEEK KLNVAHGLAW SYYIGYLRLI LPGLQARIRM FNQLHNNMLS GAGSRRLYIL FPLDCGVPDN LSVVDPNIRF RDMLPQQNID RAGIKNRVYS NSVYEILENG QPAGVCILEY ATPLQTLFAM SQDAKAGFSR EDRLEQAKLF CRTLEEILED VPESRNNCRL IVYQEPTDGN SFSLSQEVLR HIRQEEKEEV TMNAPMTSVA PPPSVLSQEP RLLISGMDQP LPLRTDLI //