STING_MOUSE
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 03-AUG-2022, entry version 135.
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},
GN Mita {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 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 [26] {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 [27] {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). Innate immune
CC response is triggered in response to non-CpG double-stranded DNA from
CC viruses and bacteria delivered to the cytoplasm (PubMed:18818105,
CC PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264).
CC Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-
CC GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic
CC GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus
CC in the cytosol (PubMed:21947006, PubMed:23722158, PubMed:23258412,
CC PubMed:23519410, PubMed:23910378). Upon binding of c-di-GMP or cGAMP,
CC STING1 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). 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). The autophagy- and interferon-inducing
CC activities can be uncoupled and autophagy induction is independent of
CC TBK1 phosphorylation (By similarity). Autophagy is also triggered upon
CC infection by bacteria: following c-di-GMP-binding, which is produced by
CC live Gram-positive bacteria, promotes reticulophagy (PubMed:29056340).
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 The preference for 2'-3'-cGAMP, compared to other linkage isomers is
CC probably due to the ligand itself, whichs adopts an organized free-
CC ligand conformation that resembles the STING1-bound conformation and
CC pays low energy costs in changing into the active conformation (By
CC similarity). May be involved in translocon function, the translocon
CC possibly being able to influence the induction of type I interferons
CC (By similarity). May be involved in transduction of apoptotic signals
CC via its association with the major histocompatibility complex class II
CC (MHC-II) (PubMed:18559423). {ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:18818105,
CC ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740,
CC ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:23258412,
CC ECO:0000269|PubMed:23519410, ECO:0000269|PubMed:23722158,
CC ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800,
CC ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263,
CC ECO:0000269|PubMed:26669264, ECO:0000269|PubMed:27324217,
CC ECO:0000269|PubMed:28529930, ECO:0000269|PubMed:29056340,
CC ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238}.
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 DDX58/RIG-I, 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 STEEP; the interaction is
CC increased upon cGAMP binding and promotes STING1 translocation to COPII
CC vesicles (By similarity). Interacts with SEC24A, SEC24B and SEC24C;
CC promoting translocation to COPII vesicles (By similarity). Interacts
CC (when ubiquitinated) with SQSTM1; leading to relocalization to
CC autophagosomes (PubMed:29496741). Interacts with SURF4 (By similarity).
CC Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with ZDHHC1;
CC ZDHHC1 constitutively interacts with STING1 and in presence of DNA
CC viruses activates it by promoting its cGAMP-induced oligomerization and
CC the recruitment of downstream signaling components (By similarity).
CC Interacts with ZDHHC11; in presence of DNA viruses promotes the
CC recruitment of IRF3 to STING1 (By similarity). Interacts with TOMM70
CC (By similarity). Interacts with IFI204 (PubMed:28529930).
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 -!- 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}; 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}; Multi-
CC pass 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}. Note=In response to double-stranded DNA
CC stimulation, translocates from the endoplasmic reticulum through the
CC endoplasmic reticulum-Golgi intermediate compartment and Golgi to post-
CC Golgi 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.
CC {ECO:0000250|UniProtKB:Q86WV6}.
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). {ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:25636800,
CC ECO:0000269|PubMed:27637147}.
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). {ECO:0000250|UniProtKB:Q86WV6,
CC 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};
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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; 11.
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 iPTMnet; Q3TBT3; -.
DR PhosphoSitePlus; Q3TBT3; -.
DR SwissPalm; Q3TBT3; -.
DR EPD; Q3TBT3; -.
DR MaxQB; Q3TBT3; -.
DR PaxDb; Q3TBT3; -.
DR PeptideAtlas; Q3TBT3; -.
DR PRIDE; Q3TBT3; -.
DR ProteomicsDB; 258752; -. [Q3TBT3-1]
DR ProteomicsDB; 258753; -. [Q3TBT3-2]
DR ProteomicsDB; 258754; -. [Q3TBT3-3]
DR Antibodypedia; 26796; 774 antibodies from 42 providers.
DR Ensembl; ENSMUST00000115728; ENSMUSP00000111393; ENSMUSG00000024349. [Q3TBT3-1]
DR Ensembl; ENSMUST00000235495; ENSMUSP00000157789; ENSMUSG00000024349. [Q3TBT3-3]
DR Ensembl; ENSMUST00000237919; ENSMUSP00000157408; ENSMUSG00000024349. [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 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; FAMSQYG; -.
DR OrthoDB; 865174at2759; -.
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 75 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 170 other tissues.
DR ExpressionAtlas; Q3TBT3; baseline and differential.
DR Genevisible; Q3TBT3; MM.
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: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:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:1990701; C:integral component of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane; ISO:MGI.
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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
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: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:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:ComplexPortal.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; 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:0032092; P:positive regulation of protein binding; ISO:MGI.
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; cd12146; STING_C; 1.
DR Gene3D; 3.40.50.12100; -; 1.
DR InterPro; IPR029158; STING.
DR InterPro; IPR033952; STING_C.
DR InterPro; IPR038623; STING_C_sf.
DR PANTHER; PTHR34339; PTHR34339; 1.
DR Pfam; PF15009; TMEM173; 1.
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; Isopeptide bond; Lipoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW 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="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000269|PubMed:23519410,
FT ECO:0007744|PDB:4KBY"
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="cyclic di-3',5'-guanylate"
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="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="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000269|PubMed:23519410,
FT ECO:0007744|PDB:4KBY"
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 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; BAE34068/BAE42310/BAE42224/
FT 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
