STING_DROEU
ID STING_DROEU Reviewed; 345 AA.
AC P0DV10;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=Stimulator of interferon genes protein homolog;
GN Name=Sting;
OS Drosophila eugracilis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=29029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=34279216; DOI=10.7554/elife.66405;
RA Kim B.Y., Wang J.R., Miller D.E., Barmina O., Delaney E., Thompson A.,
RA Comeault A.A., Peede D., D'Agostino E.R., Pelaez J., Aguilar J.M., Haji D.,
RA Matsunaga T., Armstrong E.E., Zych M., Ogawa Y., Stamenkovic-Radak M.,
RA Jelic M., Veselinovic M.S., Tanaskovic M., Eric P., Gao J.J., Katoh T.K.,
RA Toda M.J., Watabe H., Watada M., Davis J.S., Moyle L.C., Manoli G.,
RA Bertolini E., Kostal V., Hawley R.S., Takahashi A., Jones C.D., Price D.K.,
RA Whiteman N., Kopp A., Matute D.R., Petrov D.A.;
RT "Highly contiguous assemblies of 101 drosophilid genomes.";
RL Elife 10:0-0(2021).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 150-340 IN COMPLEX WITH
RP 3'2'-CGAMP, FUNCTION, 3',2'-CGAMP-BINDING, AND MUTAGENESIS OF ASN-159;
RP TYR-164; ARG-229; ARG-234 AND GLU-257.
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).
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:34261127). Recognizes and binds cyclic di-
CC GMP (c-di-GMP), a cyclic dinucleotide messenger produced by bacteria
CC such as L.monocytogenes, leading to activation of the peptidoglycan
CC recognition protein (IMD) signaling pathway and activation of Rel
CC (Relish) (By similarity). Innate immune response is triggered in
CC response to double-stranded RNA from viruses delivered to the
CC cytoplasm: Sting acts by specifically binding cyclic dinucleotides
CC 3',2'-cGAMP and 2',3'-cGAMP produced by cGLR1 and cGLR2 in response to
CC RNA virus in the cytosol (PubMed:34261127). Has a strong preference for
CC 3',2'-cGAMP compared to other cyclic dinucleotides such as 2',3'-cGAMP
CC or 3'3'-c-di-GMP (PubMed:34261127). Upon binding to 3',2'-cGAMP,
CC activates an antiviral immune response, leading to the activation of
CC Rel (Relish) (PubMed:34261127). Activated in brain in response to Zika
CC virus infection, leading to autophagy (By similarity).
CC {ECO:0000250|UniProtKB:A0A0B4LFY9, ECO:0000269|PubMed:34261127}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A0A0B4LFY9}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}.
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DR PDB; 7MWY; X-ray; 1.84 A; A=150-340.
DR PDB; 7MWZ; X-ray; 2.00 A; A=1-345.
DR PDBsum; 7MWY; -.
DR PDBsum; 7MWZ; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0140704; F:3',2'-cyclic GMP-AMP binding; IDA:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; IEA:InterPro.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0061059; P:positive regulation of peptidoglycan recognition protein signaling pathway; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:InterPro.
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; Antiviral defense; Endoplasmic reticulum; Glycoprotein;
KW Immunity; Innate immunity; Membrane; Nucleotide-binding; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..345
FT /note="Stimulator of interferon genes protein homolog"
FT /id="PRO_0000454450"
FT TRANSMEM 90..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 159
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT BINDING 234
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT BINDING 237
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT BINDING 257
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT BINDING 260
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT BINDING 264
FT /ligand="3',2'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:177334"
FT /evidence="ECO:0000269|PubMed:34261127,
FT ECO:0007744|PDB:7MWZ"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 159
FT /note="N->S,A: Reduced ability to recognize and bind 3',2'-
FT cGAMP."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 164
FT /note="Y->A: Abolished binding to 3',2'-cGAMP and
FT subsequent activation."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 164
FT /note="Y->F: Does not affect binding to 3',2'-cGAMP and
FT subsequent activation."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 229
FT /note="R->A,H: Impaired ability to be activated by 3',2'-
FT cGAMP."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 234
FT /note="R->A: Impaired binding to 3',2'-cGAMP."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 257
FT /note="E->Q,A: Impaired binding to 3',2'-cGAMP."
FT /evidence="ECO:0000269|PubMed:34261127"
SQ SEQUENCE 345 AA; 40278 MW; 8BA605613572693A CRC64;
MIKEMAIANN ADEVDNEVRA EKGRKCFYLK KMIGDYIGNT VRIVATVVLA DFLQRLYRSV
VEYVHCSKYY LPEDRLWTIL RRSCTYSNKS RYLVMGFILI GFLRISVSGN YKDVVPTFKF
LAYMPLYWIF SNLGHSTLTY SSWVRDSHGL DYAAGMASNY FHGYLKLSLP ERKADGLLHR
MNVYEDKYNV TFGIKRLIIL IPDEMFINGV IQSRILEKAT PLETQFINRA GVNRPFKHAV
YRLAEKVNGK TYYFAMEGAT PMLSFFEAMH SNFSATWQMK ELKREIWLKF YTHLNELIKT
WPETRNLVEL IIYNSHDTKG DLVDVGEMLK SHMELKTKNI DEMIG
