Sting1
entrez
72512
canonical
uniprot
Q3TBT3
canonical
ensembl
ENSMUSG00000024349
resolver
ensp
ENSMUSP00000111393
resolver
ensp
ENSMUSP00000157789
resolver
ensp
ENSMUSP00000348460
resolver
genesymbol
Sting1
resolver
genesymbol_syn
Eris
resolver
genesymbol_syn
Mita
resolver
genesymbol_syn
Mpys
resolver
genesymbol_syn
STING
resolver
genesymbol_syn
Sting
resolver
genesymbol_syn
Tmem173
resolver
uniprot
A0A2R3XZC4
resolver
uniprot
A7YGY9
resolver
uniprot
Q3TAV5
resolver
uniprot
Q3TYP5
resolver
uniprot
Q3TZY8
resolver
uniprot
Q3UJW3
resolver
uniprot
Q8C227
resolver
uniprot
Q8C5Q3
resolver
uniprot
Q8K393
resolver
uniprot
Q9CZY7
resolver
uniprot_entry
A0A2R3XZC4_MOUSE
resolver
uniprot_entry
STING_MOUSE
resolver
uniprot_sec
A7YGY9
resolver
uniprot_sec
Q3TAV5
resolver
uniprot_sec
Q3TYP5
resolver
uniprot_sec
Q3TZY8
resolver
uniprot_sec
Q3UJW3
resolver
uniprot_sec
Q8C227
resolver
uniprot_sec
Q8C5Q3
resolver
uniprot_sec
Q8K393
resolver
uniprot_sec
Q9CZY7
resolver
activity_regulation
ACTIVITY REGULATION: Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, which adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (By similarity). Activated by anticancer drug 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:23910378, PubMed:26669264). Specifically inhibited by nitrofuran derivatives C-178 and C-176, which covalently bind Cys-91 and prevent palmitoylation and subsequent activation od STING1 (PubMed:29973723). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:26669264, ECO:0000269|PubMed:29973723}.
uniprot
proteins
amino_acid_sequence
MPYSNLHPAIPRPRGHRSKYVALIFLVASLMILWVAKDPPNHTLKYLALHLASHELGLLLKNLCCLAEELCHVQSRYQGSYWKAVRACLGCPIHCMAMILLSSYFYFLQNTADIYLSWMFGLLVLYKSLSMLLGLQSLTPAEVSAVCEEKKLNVAHGLAWSYYIGYLRLILPGLQARIRMFNQLHNNMLSGAGSRRLYILFPLDCGVPDNLSVVDPNIRFRDMLPQQNIDRAGIKNRVYSNSVYEILENGQPAGVCILEYATPLQTLFAMSQDAKAGFSREDRLEQAKLFCRTLEEILEDVPESRNNCRLIVYQEPTDGNSFSLSQEVLRHIRQEEKEEVTMNAPMTSVAPPPSVLSQEPRLLISGMDQPLPLRTDLI
uniprot
proteins
function
FUNCTION: Key innate immune signaling adapter that promotes the production of type I interferon (IFN-alpha and IFN-beta) in response to the presence of DNA from bacteria and viruses in the cytosol (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264, PubMed:28529930, PubMed:31346090). Innate immune response is triggered by non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm, which induces production of cyclic dinucleotides that bind and activate STING1: STING1 recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA in the cytosol (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:21947006, PubMed:23258412, PubMed:23519410, PubMed:23722158, PubMed:23910378, PubMed:26229117, PubMed:26669264). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 oligomerizes and buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). It is then phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent antiviral state (PubMed:25636800, PubMed:27324217, PubMed:29973723). Also involved in intercellular immune signaling: cross-activated by 2',3'-cGAMP previously generated in virus-infected cells, triggering type I interferon signaling in macrophages and uninfected neighboring cells to propagate and amplify the antiviral immune response (PubMed:31992625). In addition to promote the production of type I interferon, cGAS-STING signaling also activates the NF-kappa-B signaling: mechanistically, STING1 recruits TRAF6, leading to degradation of the NF-kappa-B inhibitor and subsequent translocation of NF-kappa-B into the nucleus (PubMed:32268090, PubMed:39262777, PubMed:40973797). Activation of NF-kappa-B signaling takes place in the endolysosome and is independent of type I interferon response via direct activation by RNA viruses (By similarity). Independently of type I interferon production, plays a direct role in autophagy (PubMed:30568238). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (By similarity). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (PubMed:29056340). The proton channel activity also regulates lysosome biogenesis by activating transcription factors TFEB and TFE3, driving the expression of lysosome-related genes: activated STING1 in post-Golgi vesicles induces proton efflux and lipidation of GABARAP, sequestering the FLCN-FNIP complex and blocking mTORC1-dependent inhibition of TFEB and TFE3 (PubMed:39423796, PubMed:39689715, PubMed:40185098). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (PubMed:18559423). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23519410, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26669264, ECO:0000269|PubMed:27324217, ECO:0000269|PubMed:28529930, ECO:0000269|PubMed:29056340, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:31992625, ECO:0000269|PubMed:32268090, ECO:0000269|PubMed:39262777, ECO:0000269|PubMed:39423796, ECO:0000269|PubMed:39689715, ECO:0000269|PubMed:40185098, ECO:0000269|PubMed:40973797}.
uniprot
proteins
mass_dalton
42830
uniprot
proteins
mutagenesis
MUTAGEN 19; /note="K->R: Strong loss of MARCHF5-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:37916870"; MUTAGEN 64..65; /note="CC->SS: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 88..91; /note="CLGC->SLGS: Abolished palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 91; /note="C->A,S: Abolished inhibition by nitrofuran derivatives C-178 and C-176; abolished palmitoylation."; /evidence="ECO:0000269|PubMed:29973723"; MUTAGEN 147; /note="C->S: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 161; /note="S->A: Decrease in cGAMP-binding."; /evidence="ECO:0000269|PubMed:23258412"; MUTAGEN 205; /note="C->S: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 229; /note="I->A,G,T: Strongly decreases affinity for the synthetic compound 5,6-dimethylxanthenone 4-acetic acid (DMXAA)."; /evidence="ECO:0000269|PubMed:26669264"; MUTAGEN 239; /note="Y->S: Strong decrease in cGAMP-binding."; /evidence="ECO:0000269|PubMed:23258412"; MUTAGEN 241; /note="N->A: Strong decrease in cGAMP-binding."; /evidence="ECO:0000269|PubMed:23258412"; MUTAGEN 256; /note="C->S: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 291; /note="C->S: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 308; /note="C->S: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:27324217"; MUTAGEN 326..327; /note="QE->AA: Decreased relocalization to autophagosomes and subsequent degradation."; /evidence="ECO:0000269|PubMed:27637147"; MUTAGEN 337; /note="K->R: Abolished sumoylation by TRIM38, leading to decreased stability."; /evidence="ECO:0000269|PubMed:27637147"; MUTAGEN 357; /note="S->A: Induces a decrease in phosphorylation by TBK1, leading to reduced ability to activate IRF3."; /evidence="ECO:0000269|PubMed:25636800"; MUTAGEN 365; /note="S->A: Abolished ability to activate IRF3."; /evidence="ECO:0000269|PubMed:25636800"; MUTAGEN 373; /note="L->A: Impaired activation of IRF3 and NF-kappa-B signaling."; /evidence="ECO:0000269|PubMed:39262777
uniprot
proteins
post_translational_modification
PTM: Formation of an interchain disulfide bond at Cys-147 is essential for stabilizing STING1 dimers into higher-order homooligomers upon activation. {ECO:0000250|UniProtKB:Q86WV6}.; PTM: Phosphorylation by TBK1 leads to activation and production of IFN-beta (By similarity). Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-365 in the pLxIS motif (By similarity). The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (PubMed:27637147). Phosphorylation at Ser-365 is also required for association with the AP-1 complex (By similarity). The phosphorylated pLxIS motif facilitates SENP2 recruitment during late phase of viral infection (PubMed:27637147). Dephosphorylation by PPP6C leads to inactivation and decreased production of IFN-beta (By similarity). Phosphorylation at Ser-357 and Ser-365 by IKBKE/IKKE promotes activation of NF-kappa-B signaling (PubMed:39262777). Phosphorylation at Ser-357 is also required to activate IRF3 and may be specific for activation of NF-kappa-B signaling (PubMed:25636800). Phosphorylation at Ser-354 by MAP3K7/TAK1 facilitates its interaction with STEEP1, promoting STING1 translocation to COPII vesicles (PubMed:37832545). Phosphorylation at Tyr-244 by EGFR promotes the activation of the cGAS-STING pathway and induction of type-I interferons, while inhibiting ability to promote autophagy (By similarity). Phosphorylated on tyrosine residues upon MHC-II aggregation (PubMed:18559423). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:18559423, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:39262777}.; PTM: Ubiquitinated (PubMed:29496741). Ubiquitinated via 'Lys-63'-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1 (PubMed:29496741). 'Lys-63'-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta (By similarity). 'Lys-63'-linked ubiquitination mediated by RNF115 and/or TRIM69 promotes homodimerization and activation (By similarity). 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation (By similarity). 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination (By similarity). 'Lys-27'- and 'Lys-29'-linked polyubiquitination at Lys-288 mediated by TRIM10 promotes homooligomerization and activation (By similarity). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated by USP20; leading to its stabilization and promotion of innate antiviral response (By similarity). 'Lys-48'-linked deubiquitinated by USP44; leading to its stabilization and promotion of innate antiviral response (By similarity). Deubiquitinated by USP13; leading to inhibition of innate antiviral response (By similarity). 'Lys-63'-linked deubiquitinated by USP49; leading to inhibition of the subsequent recruitment of TBK1 to the signaling complex (By similarity). 'Lys-63'-linked ubiquitination mediated by RNF39 promotes the activation of the cGAS-STING pathway (By similarity). MARCHF5-mediated ubiquitination prevents the oxidation-induced polymer formation (PubMed:37916870). Ubiquitinated by Trim30a/TRIM30alpha at Lys-275, leading to its degradation by the proteasome (PubMed:26114947). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:26114947, ECO:0000269|PubMed:29496741}.; PTM: Sumoylated at Lys-337 by TRIM38 during the early phase of viral infection, promoting its stability by preventing its relocalization to autophagosomes and subsequent degradation (PubMed:27637147). Desumoylated by SENP2 during the late phase of viral infection (PubMed:27637147). {ECO:0000269|PubMed:27637147}.; PTM: Palmitoylation takes place in the Golgi apparatus and creates a platform for the recruitment of TBK1 (PubMed:29973723). Palmitoylation at Cys-64 enables subsequent STING1 oligomerization, ensuring proper conformation and subsequent downstream recruitment of TBK1 (By similarity). Palmitoylation at Cys-64 is also required to prevent inappropriate disulfide formation at Cys-147 in absence of cGAMP (By similarity). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:29973723}.; PTM: Alkylated via a non-enzymatic covalent modification (PubMed:37624697). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-147, preventing activity (PubMed:37624697). Also alkylated by 4-octyl itaconate, a non-physiological metabolite, inhibiting STING1 activity (PubMed:37624697). {ECO:0000269|PubMed:37624697}.; PTM: Carbonylated at Cys-88, inhibiting palmitoylation and preventing STING1 activation. Carbonylation takes place in the absence of GPX4, generating lipid peroxidation and production of 4-hydroxynonenal. {ECO:0000250|UniProtKB:Q86WV6}.
uniprot
proteins
protein_family
STING family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18559423
uniprot
proteins
pubmed
18724357
uniprot
proteins
pubmed
18818105
uniprot
proteins
pubmed
19433799
uniprot
proteins
pubmed
19776740
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21892174
uniprot
proteins
pubmed
21947006
uniprot
proteins
pubmed
23258412
uniprot
proteins
pubmed
23519410
uniprot
proteins
pubmed
23722158
uniprot
proteins
pubmed
23910378
uniprot
proteins
pubmed
25636800
uniprot
proteins
pubmed
26114947
uniprot
proteins
pubmed
26229117
uniprot
proteins
pubmed
26300263
uniprot
proteins
pubmed
26669264
uniprot
proteins
pubmed
27324217
uniprot
proteins
pubmed
27637147
uniprot
proteins
pubmed
28529930
uniprot
proteins
pubmed
28930687
uniprot
proteins
pubmed
29056340
uniprot
proteins
pubmed
29496741
uniprot
proteins
pubmed
29973723
uniprot
proteins
pubmed
30568238
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
31346090
uniprot
proteins
pubmed
31992625
uniprot
proteins
pubmed
32268090
uniprot
proteins
pubmed
37624697
uniprot
proteins
pubmed
37832545
uniprot
proteins
pubmed
37916870
uniprot
proteins
pubmed
39262777
uniprot
proteins
pubmed
39423796
uniprot
proteins
pubmed
39689715
uniprot
proteins
pubmed
39947179
uniprot
proteins
pubmed
40185098
uniprot
proteins
pubmed
40973797
uniprot
proteins
sequence_length
378
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate compartment membrane {ECO:0000269|PubMed:28930687, ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:37832545}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:27324217, ECO:0000269|PubMed:31346090, ECO:0000269|PubMed:37832545}; Multi-pass membrane protein {ECO:0000255}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q86WV6}. Golgi apparatus membrane {ECO:0000269|PubMed:27324217, ECO:0000269|PubMed:29973723}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:29056340, ECO:0000269|PubMed:29496741}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:31346090}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane {ECO:0000269|PubMed:18559423}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:18559423}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to the endoplasmic reticulum when inactive (By similarity). Following activation by cyclic dinucleotides, such as cGAMP, translocates from the endoplasmic reticulum to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) in a COPII vesicles-dependent process, where the kinase TBK1 is recruited (By similarity). Translocation to the ERGIC compartment is also dependent on cholesterol and phosphoinositide, such as phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), which directly bind STING1 at the interface between dimers and promote STING1 homooligomerization (By similarity). STING1-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis (By similarity). Activates NF-kappa-B signaling when localized to the endolysosome compartment (By similarity). Localizes in the lysosome membrane in a TMEM203-dependent manner (PubMed:31346090). {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:31346090}.
uniprot
proteins
transmembrane_region
TRANSMEM 18..34; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q86WV6"; TRANSMEM 45..69; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q86WV6"; TRANSMEM 92..106; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q86WV6"; TRANSMEM 116..133; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q86WV6
uniprot
proteins