STING_HUMAN
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 03-AUG-2022, entry version 154.
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},
GN MITA {ECO:0000303|PubMed:18818105, ECO:0000303|PubMed:19285439},
GN STING {ECO:0000303|PubMed:18724357, ECO:0000303|PubMed:26669264},
GN TMEM173 {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 DDX58 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 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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
RP INTERACTION WITH STEEP; 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 [41]
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 [42]
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 [43]
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 [44]
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 [45] {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 [46] {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 [47] {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 [48] {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 [49] {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 [50] {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 [51] {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 [52] {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 [53] {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 [54] {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 [55]
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 [56] {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 [57]
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 [58]
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 [59]
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). 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, and cyclic GMP-AMP (cGAMP), a messenger produced
CC by CGAS in response to DNA virus in the cytosol (PubMed:21947006,
CC PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:26229117,
CC PubMed:23910378, PubMed:23747010, PubMed:30842659). Upon binding of c-
CC di-GMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic
CC reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to
CC recruitment and subsequent activation of the transcription factor IRF3
CC to induce expression of type I interferon and exert a potent anti-viral
CC state (PubMed:22394562, PubMed:25636800, PubMed:29973723,
CC PubMed:30842653, PubMed:35045565). 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). The autophagy- and interferon-inducing
CC activities can be uncoupled and autophagy induction is independent of
CC TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). 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 (By similarity). Exhibits 2',3' phosphodiester linkage-
CC specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-
CC cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3'
CC linked cGAMP (PubMed:26300263, PubMed:23910378, PubMed:23747010). The
CC 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
CC (PubMed:26150511). May be involved in translocon function, the
CC translocon possibly being able to influence the induction of type I
CC interferons (PubMed:18724357). May be involved in transduction of
CC apoptotic signals via its association with the major histocompatibility
CC 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:29973723,
CC ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:30842653,
CC ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662,
CC ECO:0000269|PubMed:35045565}.
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 -!- 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). {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 -!- 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 (Probable). Interacts (when phosphorylated) with IRF3;
CC following activation and phosphorylation on the pLxIS motif by TBK1,
CC recruits IRF3 (PubMed:22394562, PubMed:25636800, PubMed:28331227,
CC PubMed:27302953). Interacts with DDX58/RIG-I, MAVS and SSR2
CC (PubMed:18818105, PubMed:18724357). Interacts with RNF5 and TRIM56
CC (PubMed:19285439, PubMed:21074459). Interacts with TBK1; when
CC 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 STEEP; the interaction is
CC increased upon cGAMP binding and promotes STING1 translocation to COPII
CC vesicles (PubMed:32690950). Interacts with SEC24A, SEC24B, and SEC24C;
CC promoting translocation to COPII vesicles (PubMed:32690950,
CC PubMed:30842662). Interacts (when ubiquitinated) with SQSTM1; leading
CC to relocalization to autophagosomes (By similarity). Interacts with
CC SURF4 (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). {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:30842659, ECO:0000269|PubMed:30842662,
CC ECO:0000269|PubMed:31320558, 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 and UL42; these interactions result in the inhibition of
CC cGAS-STING signaling. {ECO:0000269|PubMed:31107917,
CC ECO:0000269|PubMed:33057424}.
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; O95786-1: DDX58; NbExp=2; IntAct=EBI-2800345, EBI-15577823;
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; 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}; Multi-pass membrane protein {ECO:0000255,
CC ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:32690950}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:19433799,
CC ECO:0000269|PubMed:29694889, ECO:0000269|PubMed:30842653}. Endoplasmic
CC reticulum-Golgi intermediate compartment membrane
CC {ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:32690950}; Multi-pass
CC membrane protein {ECO:0000255, ECO:0000269|PubMed:32690950}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:30842653}; Multi-pass membrane
CC protein {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 {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 -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed in skin
CC endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium
CC and alveolar macrophages. {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). {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}.
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). {ECO:0000250|UniProtKB:Q3TBT3,
CC ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:19433799,
CC ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:25254379}.
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 ---------------------------------------------------------------------------
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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; 6RM0; X-ray; 2.51 A; A=140-343.
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; 6YWA; X-ray; 2.31 A; A/B=140-343.
DR PDB; 7KVX; X-ray; 2.48 A; A=140-379.
DR PDB; 7KW1; X-ray; 1.80 A; A=140-379.
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; 6RM0; -.
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; 6YWA; -.
DR PDBsum; 7KVX; -.
DR PDBsum; 7KW1; -.
DR AlphaFoldDB; Q86WV6; -.
DR SMR; Q86WV6; -.
DR BioGRID; 130988; 102.
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.ENSP00000331288; -.
DR BindingDB; Q86WV6; -.
DR ChEMBL; CHEMBL4523377; -.
DR GuidetoPHARMACOLOGY; 2902; -.
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; Q86WV6; -.
DR PeptideAtlas; Q86WV6; -.
DR PRIDE; Q86WV6; -.
DR ProteomicsDB; 70211; -.
DR Antibodypedia; 26796; 774 antibodies from 42 providers.
DR CPTC; Q86WV6; 1 antibody.
DR DNASU; 340061; -.
DR Ensembl; ENST00000330794.9; ENSP00000331288.4; ENSG00000184584.13.
DR Ensembl; ENST00000651699.1; ENSP00000499166.1; ENSG00000184584.13.
DR Ensembl; ENST00000652271.1; ENSP00000498596.1; ENSG00000184584.13.
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 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; FAMSQYG; -.
DR OrthoDB; 865174at2759; -.
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-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q86WV6; -.
DR SIGNOR; Q86WV6; -.
DR BioGRID-ORCS; 340061; 13 hits in 1085 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 97 other tissues.
DR ExpressionAtlas; Q86WV6; baseline and differential.
DR Genevisible; Q86WV6; HS.
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:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:FlyBase.
DR GO; GO:1990701; C:integral component of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) 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; IC: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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:BHF-UCL.
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: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:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
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; cd12146; STING_C; 1.
DR DisProt; DP01602; -.
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; Autophagy; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Disease variant; Endoplasmic reticulum; Golgi apparatus;
KW Host-virus interaction; Immunity; Innate immunity; Isopeptide bond;
KW Lipoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; 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:0007744|PDB:4LOH"
FT BINDING 162
FT /ligand="cyclic di-3',5'-guanylate"
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="cyclic di-3',5'-guanylate"
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="cyclic di-3',5'-guanylate"
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:0007744|PDB:4KSY,
FT ECO:0007744|PDB:4LOH"
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:0007744|PDB:4KSY,
FT ECO:0007744|PDB:4LOH"
FT BINDING 263
FT /ligand="cyclic di-3',5'-guanylate"
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 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 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 3'-
FT 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 (probable disease-associated variant found in
FT a 9-month-old patient who died following a fever and severe
FT neck abscess without indication of any severe bacterial
FT infection; 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 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 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->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 senstive to 5,6-dimethylxanthenone 4-acetic acid
FT (DMXAA) drug, leading to activation of the STING1 pathway.
FT Renders the enzyme senstive to 5,6-dimethylxanthenone 4-
FT acetic acid (DMXAA) drug; when 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 senstive to 5,6-
FT dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to
FT activation of the STING1 pathway."
FT /evidence="ECO:0000269|PubMed:25199835"
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 cGAMP-
FT 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 cGAMP-
FT 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 senstive to 5,6-
FT dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to
FT activation of the STING1 pathway; when associated with A-
FT 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: Abrogates interaction with STEEP."
FT /evidence="ECO:0000269|PubMed:32690950"
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 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 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 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