STING_XENTR
ID STING_XENTR Reviewed; 329 AA.
AC A8E5V9;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:26300263};
DE Short=STING {ECO:0000303|PubMed:26300263};
DE AltName: Full=Transmembrane protein 173 {ECO:0000305};
GN Name=sting1 {ECO:0000250|UniProtKB:Q86WV6};
GN Synonyms=sting {ECO:0000303|PubMed:26300263},
GN tmem173 {ECO:0000250|UniProtKB:Q86WV6};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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).
CC -!- FUNCTION: Sensor of cytosolic DNA from bacteria and viruses that
CC promotes autophagy. Acts by recognizing and binding cyclic GMP-AMP
CC (cGAMP), a messenger produced by CGAS in response to DNA in the cytosol
CC (PubMed:26300263, PubMed:30842662). Following cGAMP-binding, promotes
CC the formation of autophagosomes, leading to target cytosolic DNA for
CC degradation by the lysosome (PubMed:30842662). Exhibits guanine base-
CC specific ligand recognition. Binds 3'-3'linked cGAMP, 2'-3' linked
CC cGAMP and 3'-3' linked c-di-GMP with much greater affinity as compared
CC to 3'-3' linked c-di-AMP (PubMed:26300263). Lacks the C-terminal tail
CC (CTT) found in other vertebrate orthologs which is essential for
CC interferon signaling (PubMed:26300263). {ECO:0000269|PubMed:26300263,
CC ECO:0000269|PubMed:30842662}.
CC -!- SUBUNIT: Homodimer; forms a homodimer in absence of cyclic nucleotide
CC (c-di-GMP or cGAMP). Homotetramer; in presence of cyclic nucleotide (c-
CC di-GMP or cGAMP), forms tetramers and higher-order oligomers through
CC side-by-side packing. {ECO:0000250|UniProtKB:E1C7U0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30842662}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q86WV6}. Endoplasmic reticulum-Golgi
CC intermediate compartment membrane {ECO:0000250|UniProtKB:Q86WV6};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; 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:30842662). Upon
CC cGAMP-binding, translocates to the endoplasmic reticulum-Golgi
CC intermediate compartment (ERGIC) in a process that is dependent on
CC COPII vesicles; STING1-containing ERGIC serves as a membrane source for
CC LC3 lipidation, which is a key step in autophagosome biogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:30842662}.
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).
CC {ECO:0000250|UniProtKB:E1C7U0, ECO:0000250|UniProtKB:Q86WV6}.
CC -!- DOMAIN: The N-terminal domain interacts with glycerophospholipids and
CC phospholipids. {ECO:0000250|UniProtKB:Q86WV6}.
CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}.
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DR EMBL; BC153736; AAI53737.1; -; mRNA.
DR RefSeq; NP_001106445.2; NM_001112974.1.
DR AlphaFoldDB; A8E5V9; -.
DR SMR; A8E5V9; -.
DR STRING; 8364.ENSXETP00000055434; -.
DR PaxDb; A8E5V9; -.
DR PRIDE; A8E5V9; -.
DR DNASU; 100127621; -.
DR GeneID; 100127621; -.
DR KEGG; xtr:100127621; -.
DR CTD; 340061; -.
DR Xenbase; XB-GENE-5880492; sting1.
DR eggNOG; ENOG502R15M; Eukaryota.
DR InParanoid; A8E5V9; -.
DR OrthoDB; 865174at2759; -.
DR Reactome; R-XTR-1834941; STING mediated induction of host immune responses.
DR Reactome; R-XTR-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-XTR-3249367; STAT6-mediated induction of chemokines.
DR Reactome; R-XTR-3270619; IRF3-mediated induction of type I IFN.
DR Reactome; R-XTR-6798695; Neutrophil degranulation.
DR Proteomes; UP000008143; Chromosome 3.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IDA:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0061709; P:reticulophagy; ISS: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 2: Evidence at transcript level;
KW Autophagy; Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Golgi apparatus; Immunity; Innate immunity; Membrane; Nucleotide-binding;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..329
FT /note="Stimulator of interferon genes protein"
FT /id="PRO_0000355181"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 5..25
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 27..52
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 75..88
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..98
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 99..116
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 135..325
FT /note="Cyclic dinucleotide-binding domain (CBD)"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 144
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 144
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 149
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 149
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 220..223
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 220
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 245
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 245
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
SQ SEQUENCE 329 AA; 37815 MW; 66F389EB83EC7199 CRC64;
MACVLAIGSI LFVWILGKGK YSGAQLIYRM ATNFAISQGC CLVTCACELT EEIKHLHTRY
NGHYWRALKA SFNLSCAAFV TAILCYVFYE PKLMASLPLT IDITLTLLSW LFCWILGIQG
PTPATISEIT EIKQLNVAHG LAWSYYVGYL QFVLPALKES IQKFNEENHN LLKFPETCRL
HILIPLSCRL YGDLKDVDEN ITFLKEIPPL YIDRAGIKGR VFKNNVYRIL DEDGRPYNCI
VEYATPLASL LKMTDIPSAA FSADDRLQQT KLFYRTLKDI LENAHELQNT YRLIVYEDFP
ETKDHSRHLL SQEILKHIRQ QHSEEYSML
