STING_DROME
ID STING_DROME Reviewed; 343 AA.
AC A0A0B4LFY9; Q6AWJ4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Stimulator of interferon genes protein homolog {ECO:0000305};
DE Short=dSTING {ECO:0000303|PubMed:29934091};
DE Short=dmSTING {ECO:0000303|PubMed:29924997};
GN Name=Sting {ECO:0000312|FlyBase:FBgn0033453};
GN ORFNames=CG1667 {ECO:0000312|FlyBase:FBgn0033453};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Larva, and Pupae;
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Rubin G.M., Celniker S.;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=29934091; DOI=10.1016/j.chom.2018.05.022;
RA Liu Y., Gordesky-Gold B., Leney-Greene M., Weinbren N.L., Tudor M.,
RA Cherry S.;
RT "Inflammation-induced, STING-dependent autophagy restricts Zika virus
RT infection in the Drosophila brain.";
RL Cell Host Microbe 24:57-68(2018).
RN [5]
RP FUNCTION.
RX PubMed=29924997; DOI=10.1016/j.celrep.2018.05.029;
RA Martin M., Hiroyasu A., Guzman R.M., Roberts S.A., Goodman A.G.;
RT "Analysis of Drosophila STING reveals an evolutionarily conserved
RT antimicrobial function.";
RL Cell Rep. 23:3537-3550(2018).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=30119996; DOI=10.1016/j.immuni.2018.07.013;
RA Goto A., Okado K., Martins N., Cai H., Barbier V., Lamiable O., Troxler L.,
RA Santiago E., Kuhn L., Paik D., Silverman N., Holleufer A., Hartmann R.,
RA Liu J., Peng T., Hoffmann J.A., Meignin C., Daeffler L., Imler J.L.;
RT "The kinase IKKbeta regulates a STING- and NF-kappaB-dependent antiviral
RT response pathway in Drosophila.";
RL Immunity 49:225-234(2018).
RN [7]
RP FUNCTION.
RX PubMed=33262294; DOI=10.1126/scisignal.abc4537;
RA Cai H., Holleufer A., Simonsen B., Schneider J., Lemoine A., Gad H.H.,
RA Huang J., Huang J., Chen D., Peng T., Marques J.T., Hartmann R.,
RA Martins N.E., Imler J.L.;
RT "2'3'-cGAMP triggers a STING- and NF-kappaB-dependent broad antiviral
RT response in Drosophila.";
RL Sci. Signal. 13:0-0(2020).
RN [8]
RP FUNCTION, AND 3',2'-CGAMP-BINDING.
RX PubMed=34261127; DOI=10.1038/s41586-021-03743-5;
RA Slavik K.M., Morehouse B.R., Ragucci A.E., Zhou W., Ai X., Chen Y., Li L.,
RA Wei Z., Baehre H., Koenig M., Seifert R., Lee A.S.Y., Cai H., Imler J.L.,
RA Kranzusch P.J.;
RT "cGAS-like receptors sense RNA and control 3'2'-cGAMP signaling in
RT Drosophila.";
RL Nature 597:109-113(2021).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=34261128; DOI=10.1038/s41586-021-03800-z;
RA Holleufer A., Winther K.G., Gad H.H., Ai X., Chen Y., Li L., Wei Z.,
RA Deng H., Liu J., Frederiksen N.A., Simonsen B., Andersen L.L.,
RA Kleigrewe K., Dalskov L., Pichlmair A., Cai H., Imler J.L., Hartmann R.;
RT "Two cGAS-like receptors induce antiviral immunity in Drosophila.";
RL Nature 597:114-118(2021).
CC -!- FUNCTION: Facilitator of innate immune signaling that binds cyclic
CC dinucleotides produced in response to infection by bacteria and/or
CC viruses, and promotes the activation of the NF-kappa-B transcription
CC factor Rel (Relish) (PubMed:29934091, PubMed:29924997, PubMed:30119996,
CC PubMed:33262294, PubMed:34261127, PubMed:34261128). Recognizes and
CC binds cyclic di-GMP (c-di-GMP), a cyclic dinucleotide messenger
CC produced by bacteria such as L.monocytogenes, leading to activation of
CC the peptidoglycan recognition protein (IMD) signaling pathway and
CC activation of Rel (Relish) (PubMed:29924997). Innate immune response is
CC triggered in response to double-stranded RNA from viruses delivered to
CC the cytoplasm: Sting acts by specifically binding cyclic dinucleotides
CC 3',2'-cGAMP and 2',3'-cGAMP produced by cGLR1 (CG12970) and cGLR2
CC (CG30424) in response to RNA virus in the cytosol (PubMed:34261127,
CC PubMed:34261128). Has a strong preference for 3',2'-cGAMP compared to
CC other cyclic dinucleotides such as 2',3'-cGAMP or 3'3'-c-di-GMP
CC (PubMed:34261127). Upon binding to 3',2'-cGAMP, activates an antiviral
CC immune response, leading to the activation of Rel (Relish)
CC (PubMed:34261127, PubMed:34261128). Activated in brain in response to
CC Zika virus infection, leading to autophagy (PubMed:29934091).
CC {ECO:0000269|PubMed:29924997, ECO:0000269|PubMed:29934091,
CC ECO:0000269|PubMed:30119996, ECO:0000269|PubMed:33262294,
CC ECO:0000269|PubMed:34261127, ECO:0000269|PubMed:34261128}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30119996}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Expression is directly activated by Rel (Relish).
CC {ECO:0000269|PubMed:30119996, ECO:0000269|PubMed:34261128}.
CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT94483.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF58891.3; -; Genomic_DNA.
DR EMBL; AE013599; AHN56054.1; -; Genomic_DNA.
DR EMBL; BT015254; AAT94483.1; ALT_INIT; mRNA.
DR RefSeq; NP_001286256.1; NM_001299327.1.
DR RefSeq; NP_610525.4; NM_136681.5.
DR AlphaFoldDB; A0A0B4LFY9; -.
DR SMR; A0A0B4LFY9; -.
DR IntAct; A0A0B4LFY9; 1.
DR STRING; 7227.FBpp0087563; -.
DR PaxDb; A0A0B4LFY9; -.
DR DNASU; 36016; -.
DR EnsemblMetazoa; FBtr0345019; FBpp0311270; FBgn0033453.
DR EnsemblMetazoa; FBtr0345020; FBpp0311271; FBgn0033453.
DR GeneID; 36016; -.
DR KEGG; dme:Dmel_CG1667; -.
DR CTD; 36016; -.
DR FlyBase; FBgn0033453; Sting.
DR VEuPathDB; VectorBase:FBgn0033453; -.
DR eggNOG; ENOG502R15M; Eukaryota.
DR GeneTree; ENSGT00390000008582; -.
DR HOGENOM; CLU_076442_0_0_1; -.
DR OMA; SATWQMK; -.
DR OrthoDB; 865174at2759; -.
DR PhylomeDB; A0A0B4LFY9; -.
DR BioGRID-ORCS; 36016; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36016; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033453; Expressed in oviduct (Drosophila) and 26 other tissues.
DR ExpressionAtlas; A0A0B4LFY9; baseline and differential.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:FlyBase.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IBA:GO_Central.
DR GO; GO:0140704; F:3',2'-cyclic GMP-AMP binding; ISS:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; IDA:FlyBase.
DR GO; GO:0002218; P:activation of innate immune response; IEA:InterPro.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IMP:FlyBase.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0002807; P:positive regulation of antimicrobial peptide biosynthetic process; IMP:FlyBase.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:0061059; P:positive regulation of peptidoglycan recognition protein signaling pathway; IMP:FlyBase.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:InterPro.
DR GO; GO:0061709; P:reticulophagy; IBA:GO_Central.
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 Antiviral defense; Endoplasmic reticulum; Glycoprotein; Immunity;
KW Innate immunity; Membrane; Nucleotide-binding; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..343
FT /note="Stimulator of interferon genes protein homolog"
FT /id="PRO_0000454449"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 157
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT BINDING 232
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT BINDING 235
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT BINDING 255
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT BINDING 258
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT BINDING 262
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000250|UniProtKB:P0DV10"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 343 AA; 40183 MW; A1BC95A2C05F7B3F CRC64;
MAIASNVVEA GNAVRAEKGR KYFYFRKMIG DYIDTSIRIV ATVFLADLLL RLYRCVVEYG
SNGRYYLPED RLWIILRRSC TYNNRSIYLI VGFLLVAFFR ISVTGNYRNV MPTTLFLFQM
PLYWIWSFTD MDQSTLSYSH WIRDSHGLDY AAGMASNYFH GYLKLSLPER KDDGLKHRLA
MYEDKNNVTF GIKRLVILIP DEMFVNGVLE SHLLDKAEPL ETQFINRAGV YRPFKHDVYR
MNKKVNGRTY YFAVEGATPM ISFFDATYSN LSGTWQMQEL KREIWIKFYK HLKELITTWP
ETRDLVELII YNSHDSKGNL VDVGELLVAH MQNKTKTIDE ISN
