MITA
entrez
340061
canonical
uniprot
Q86WV6
canonical
ensembl
ENSG00000184584
resolver
ensembl
ENSG00000288243
resolver
ensp
ENSP00000331288
resolver
ensp
ENSP00000498513
resolver
ensp
ENSP00000498596
resolver
ensp
ENSP00000498768
resolver
ensp
ENSP00000499166
resolver
ensp
ENSP00000499985
resolver
ensp
ENSP00000500679
resolver
ensp
ENSP00000500685
resolver
ensp
ENSP00000500793
resolver
ensp
ENSP00000500823
resolver
ensp
ENSP00000500885
resolver
ensp
ENSP00000531839
resolver
enst
ENST00000330794
resolver
enst
ENST00000651565
resolver
enst
ENST00000651699
resolver
enst
ENST00000652110
resolver
enst
ENST00000652271
resolver
enst
ENST00000672096
resolver
enst
ENST00000672102
resolver
enst
ENST00000672611
resolver
enst
ENST00000672865
resolver
enst
ENST00000673377
resolver
enst
ENST00000673523
resolver
enst
ENST00000861780
resolver
genesymbol
MITA
resolver
genesymbol
STING1
resolver
genesymbol_syn
ERIS
resolver
genesymbol_syn
MITA
resolver
genesymbol_syn
STING
resolver
genesymbol_syn
TMEM173
resolver
hgnc
HGNC:27962
resolver
uniprot
A0A494C0W5
resolver
uniprot
A0AA49X8K8
resolver
uniprot
A8K3P6
resolver
uniprot
B6EB35
resolver
uniprot
D6RBX0
resolver
uniprot
D6RE01
resolver
uniprot
D6RID9
resolver
uniprot
J3QTB1
resolver
uniprot
V5V0K2
resolver
uniprot_entry
A0A494C0W5_HUMAN
resolver
uniprot_entry
A0AA49X8K8_HUMAN
resolver
uniprot_entry
J3QTB1_HUMAN
resolver
uniprot_entry
STING_HUMAN
resolver
uniprot_entry
V5V0K2_HUMAN
resolver
uniprot_sec
A8K3P6
resolver
uniprot_sec
B6EB35
resolver
uniprot_sec
D6RBX0
resolver
uniprot_sec
D6RE01
resolver
uniprot_sec
D6RID9
resolver
activity_regulation
ACTIVITY REGULATION: STING1 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:23747010, PubMed:23910378, 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 (PubMed:26150511). Activated upon binding to the hydrolysis-resistant 2'3'-cG(s)A(s)MP, an analog of cGAMP, in which phosphodiester linkages are replaced by phosphothioate linkages (PubMed:25344812). Specifically inhibited by small-molecule H-151 (N-(4-ethylphenyl)-N'-1H-indol-3-yl-urea), which covalently binds Cys-91 and prevents palmitoylation and subsequent activation of STING1 (PubMed:29973723, PubMed:35045565). In contrast to mouse protein, not activated by anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:23910378, PubMed:25199835, PubMed:26669264). Inhibited by compound 18 ([(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]acetate), a competitive inhibitor with slow dissociation kinetics and good oral bioavailability (PubMed:30655953). Homooligomerization and ability to promote the production of type I interferons is activated by C53, a small benzothiazinone-like compound that binds to the transmembrane regions. in the area of the putative pore (PubMed:35388221). In contrast, compound C53, directly inhibits the proton channel activity and facilitate MAP1LC3B/LC3B lipidation and autophagosome formation (PubMed:37535724). Inhibited by the NVS-STG2, a glue-like compound, which induces the high-order STING1 homooligomerization by binding to a pocket between the transmembrane domains of the neighboring dimers (PubMed:37828400). {ECO:0000269|PubMed:23747010, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25199835, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:26150511, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:26669264, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30655953, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:37828400}.
uniprot
proteins
amino_acid_sequence
MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLLNGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWMLALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIRTYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVYSNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILADAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQEPELLISGMEKPLPLRTDFS
uniprot
proteins
disease_involvement
DISEASE: STING-associated vasculopathy, infantile-onset (SAVI) [MIM:615934]: An autoinflammatory disease characterized by early-onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease. {ECO:0000269|PubMed:25029335, ECO:0000269|PubMed:25401470, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:33162473, ECO:0000269|PubMed:35556195}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23747010, PubMed:23910378, PubMed:25704810, PubMed:27801882, PubMed:29973723, PubMed:30842659, PubMed:31992625, PubMed:32926474, PubMed:35045565, PubMed:35388221, PubMed:36808561, PubMed:37086726, PubMed:37832545, PubMed:39255680, PubMed:39947179). 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:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:23747010, PubMed:23910378, PubMed:26229117, PubMed:26300263, PubMed:30842659, PubMed:35388221, PubMed:37086726, PubMed:37379839). 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) (PubMed:30842662, PubMed:41639452, PubMed:41639454, PubMed:41887218). 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:22394562, PubMed:25636800, PubMed:29973723, PubMed:30643259, PubMed:30842653, PubMed:32926474, PubMed:35045565, PubMed:35388221, PubMed:38917796). 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:24077100, 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:38917796, PubMed:39262777, PubMed:40973797, PubMed:41747053). 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 (PubMed:40973797, PubMed:41747053). Independently of type I interferon production, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662, PubMed:32926474). 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 (PubMed:30842662). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (PubMed:37535724, PubMed:39947179). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). 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). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23747010, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:30643259, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:31992625, ECO:0000269|PubMed:32268090, ECO:0000269|PubMed:32926474, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:36808561, ECO:0000269|PubMed:37086726, ECO:0000269|PubMed:37379839, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:38917796, ECO:0000269|PubMed:39255680, ECO:0000269|PubMed:39262777, ECO:0000269|PubMed:39423796, ECO:0000269|PubMed:39689715, ECO:0000269|PubMed:39947179, ECO:0000269|PubMed:40973797, ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454, ECO:0000269|PubMed:41747053, ECO:0000269|PubMed:41887218}.; FUNCTION: (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230). {ECO:0000269|PubMed:26405230}.
uniprot
proteins
mass_dalton
42193
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="I->Q: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 14; /note="R->A: Abolished endoplasmic reticulum exit, leading to impaired ability to induce the production of type I interferon and activate NF-kappa-B."; /evidence="ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:40973797"; MUTAGEN 20; /note="K->A: Decreased binding to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2); when associated with A-71."; /evidence="ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454"; MUTAGEN 20; /note="K->R: Does not affect amount of ubiquitination."; /evidence="ECO:0000269|PubMed:21074459"; MUTAGEN 26; /note="L->A: Reduced homooligomerization and activation in presence of coumpond C53."; /evidence="ECO:0000269|PubMed:35388221"; MUTAGEN 30; /note="L->A: Reduced homooligomerization and activation in presence of coumpond C53."; /evidence="ECO:0000269|PubMed:35388221"; MUTAGEN 44; /note="L->A: Reduced homooligomerization and activation in presence of coumpond C53."; /evidence="ECO:0000269|PubMed:35388221"; MUTAGEN 64; /note="C->S: Decreased palmitoylation and ability to form homooligomers."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 68; /note="E->A: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 69; /note="E->A: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 71; /note="R->A: Decreased binding to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2); when associated with A-20."; /evidence="ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454"; MUTAGEN 76..78; /note="RYR->AYA: Abolishes the endoplasmic reticulum location."; /evidence="ECO:0000269|PubMed:19433799"; MUTAGEN 80; /note="S->I: Decreased binding to cholesterol and ability to form homooligomers."; /evidence="ECO:0000269|PubMed:41639452"; MUTAGEN 82; /note="W->Q: Decreased ability to form homooligomers."; /evidence="ECO:0000269|PubMed:41639452"; MUTAGEN 90; /note="G->C,A: Abolished ability to activate NF-kappa-B in response to RNA virus infection."; /evidence="ECO:0000269|PubMed:41747053"; MUTAGEN 91; /note="C->S: Abolished inhibition by small-molecule H-151; abolished palmitoylation."; /evidence="ECO:0000269|PubMed:29973723"; MUTAGEN 95; /note="R->C: Abolished activation by the glue-like compound NVS-STG2."; /evidence="ECO:0000269|PubMed:37828400"; MUTAGEN 104; /note="Y->A: Reduced homooligomerization and activation in presence of coumpond C53."; /evidence="ECO:0000269|PubMed:35388221"; MUTAGEN 137; /note="K->R: Does not affect amount of ubiquitination."; /evidence="ECO:0000269|PubMed:21074459"; MUTAGEN 148; /note="C->A: Reduced homooligomerization and exit from the endoplasmic reticulum."; /evidence="ECO:0000269|PubMed:41887218"; MUTAGEN 150; /note="K->R: Abolishes ubiquitination, homodimerization and subsequent production of IFN-beta."; /evidence="ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:25254379"; MUTAGEN 153; /note="F->A: Partially constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 158; /note="G->A: Constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 158; /note="G->E: Abolished homodimerization and activation."; /evidence="ECO:0000269|PubMed:37832545"; MUTAGEN 158; /note="G->S,V: Partially constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand."; /evidence="ECO:0000269|PubMed:30842659"; MUTAGEN 162; /note="S->A: Slight decrease in c-di-GMP-binding. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug; when associated with I-266."; /evidence="ECO:0000269|PubMed:22728658, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25199835, ECO:0000269|PubMed:26669264"; MUTAGEN 166; /note="G->S: Slight decrease in c-di-GMP-binding."; /evidence="ECO:0000269|PubMed:22728658"; MUTAGEN 178..180; /note="RIR->AIA: Abolishes the endoplasmic reticulum location."; /evidence="ECO:0000269|PubMed:19433799"; MUTAGEN 214; /note="M->E: Constitutively active mutant."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 224; /note="K->R: Abolished ubiquitination by MUL1."; /evidence="ECO:0000269|PubMed:28763789"; MUTAGEN 230; /note="G->I: Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway."; /evidence="ECO:0000269|PubMed:25199835"; MUTAGEN 236; /note="K->R: Loss of deubiquitination by USP44."; /evidence="ECO:0000269|PubMed:31968013"; MUTAGEN 238..240; /note="RVY->AVA: Strong decrease in cGAMP-binding without affecting interaction with TBK1. Abolished ability to induce autophagy."; /evidence="ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842662"; MUTAGEN 238; /note="R->A: Abolished cGAMP-binding. Abolished ability to induce autophagy."; /evidence="ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:30842662"; MUTAGEN 240; /note="Y->A: Abolished cGAMP-binding."; /evidence="ECO:0000269|PubMed:23910378"; MUTAGEN 240; /note="Y->S: Strong decrease in c-di-GMP-binding."; /evidence="ECO:0000269|PubMed:22728658"; MUTAGEN 242; /note="N->A: Strong decrease in c-di-GMP and cGAMP-binding."; /evidence="ECO:0000269|PubMed:22728658, ECO:0000269|PubMed:23910378"; MUTAGEN 245; /note="Y->F: Abolished phosphorylation by EGFR and activation of cGAS-STING signaling."; /evidence="ECO:0000269|PubMed:32926474"; MUTAGEN 260; /note="E->A: Strong decrease in c-di-GMP and cGAMP-binding."; /evidence="ECO:0000269|PubMed:22728658, ECO:0000269|PubMed:23910378"; MUTAGEN 263; /note="T->A: Strong decrease in c-di-GMP-binding."; /evidence="ECO:0000269|PubMed:22728658"; MUTAGEN 264; /note="P->A: Strong decrease in c-di-GMP-binding."; /evidence="ECO:0000269|PubMed:22728658"; MUTAGEN 266; /note="Q->I: Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway; when associated with A-162."; /evidence="ECO:0000269|PubMed:25199835"; MUTAGEN 267; /note="T->A: Strong decrease in c-di-GMP-binding."; /evidence="ECO:0000269|PubMed:22728658"; MUTAGEN 268; /note="L->F: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 269; /note="F->G: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 271; /note="M->A: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 273..277; /note="QYSQA->AYSQQ: In AQQA mutant reduced homooligomerization and ability to induce type I interferons. Abrogates interaction with STEEP1 and endoplasmic reticulum exit."; /evidence="ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:41639454, ECO:0000269|PubMed:41887218"; MUTAGEN 273; /note="Q->A: Abolished translocation from the endoplasmic reticulum in response to cGAMP-binding, leading to impaired ability to induce the production of type I interferon and activate NF-kappa-B. Reduced phosphorylation by TBK1."; /evidence="ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:40973797"; MUTAGEN 275; /note="S->N: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 277; /note="A->Q: Abolished translocation from the endoplasmic reticulum in response to cGAMP-binding, leading to impaired ability to induce the production of type I interferon and activate NF-kappa-B. Reduced phosphorylation by TBK1."; /evidence="ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:40973797"; MUTAGEN 279; /note="F->A: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 281; /note="R->E: Constitutively active mutant that prevents autoinhibition by the C-terminal tail (CTT)."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 289; /note="K->R: Decreased ubiquitination by TRIM10."; /evidence="ECO:0000269|PubMed:36972172"; MUTAGEN 301; /note="D->N: Promotes activity in absence of 2'-3'-cGAMP."; /evidence="ECO:0000269|PubMed:37086726"; MUTAGEN 315; /note="Q->A: Constitutively active mutant."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 320; /note="D->A: Constitutively active mutant."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 324..326; /note="SLS->ALA: Induces a decrease in phosphorylation by TBK1."; /evidence="ECO:0000269|PubMed:18818105"; MUTAGEN 333..334; /note="LR->AA: Abolished ability to induce autophagy. Abolished interaction with SEC24C."; /evidence="ECO:0000269|PubMed:30842662"; MUTAGEN 336; /note="E->A: Constitutively active mutant."; /evidence="ECO:0000269|PubMed:40610719"; MUTAGEN 340..343; /note="EVTV->DVVIDIE: In STING-NleA mutant; contains an optimal ER-exit motif, promoting efficient exit from the endoplasmic reticulum and a constitutively active cGAS-STING signaling."; /evidence="ECO:0000269|PubMed:41887218"; MUTAGEN 341; /note="V->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562"; MUTAGEN 342; /note="T->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562"; MUTAGEN 355; /note="S->A: Impaired ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:37832545"; MUTAGEN 358; /note="S->A: Decreased phosphorylation by TBK1, leading to reduced ability to activate IRF3."; /evidence="ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:29478775"; MUTAGEN 358; /note="S->D: Mimics phosphorylation; promotes NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:40973797"; MUTAGEN 360; /note="E->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562"; MUTAGEN 362; /note="E->A: Slightly affects ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 363; /note="L->A: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 364; /note="L->A: Slightly affects ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 365; /note="I->A: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 366; /note="S->A,N,C: Induces a decrease in phosphorylation by TBK1. Abolished ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953"; MUTAGEN 366; /note="S->D: Phosphomimetic mutant; retains some ability to activate IRF3. It probably incompletely mimics phosphorylation."; /evidence="ECO:0000269|PubMed:25636800"; MUTAGEN 367; /note="G->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562"; MUTAGEN 370; /note="K->R: Decreased ubiquitination by TRIM10."; /evidence="ECO:0000269|PubMed:36972172"; MUTAGEN 371; /note="P->Q: Abolished ability to induce the production of type I interferon."; /evidence="ECO:0000269|PubMed:30842653"; MUTAGEN 374; /note="L->A: Abolished ability to activate IRF3 and induce the production of type I interferon. Abolished ability to activate NF-kappa-B."; /evidence="ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:40973797"; MUTAGEN 375; /note="R->A: Does not affect ability to activate IRF3. Abolished ability to induce the production of type I interferon. Abolished ability to activate NF-kappa-B."; /evidence="ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:40973797"; MUTAGEN 376; /note="T->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 377; /note="D->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:22394562"; MUTAGEN 379; /note="S->A: Does not affect ability to activate IRF3."; /evidence="ECO:0000269|PubMed:27302953
uniprot
proteins
post_translational_modification
PTM: Formation of an interchain disulfide bond at Cys-148 is essential for stabilizing STING1 dimers into higher-order homooligomers upon activation. {ECO:0000269|PubMed:31230712, ECO:0000269|PubMed:40610719}.; PTM: Phosphorylation by TBK1 leads to activation and production of IFN-beta (PubMed:18818105, PubMed:19433799, PubMed:25636800, PubMed:27302953, PubMed:30842653, PubMed:30842659, PubMed:32690950). Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-366 in the pLxIS motif (PubMed:25636800, PubMed:32690950). 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:25636800). Phosphorylation at Ser-366 is also required for association with the AP-1 complex (PubMed:36261523). The phosphorylated pLxIS motif facilitates SENP2 recruitment during late phase of viral infection (By similarity). Dephosphorylation by PPP6C leads to inactivation and decreased production of IFN-beta (PubMed:32753499). Phosphorylation at Ser-358 and Ser-366 by IKBKE/IKKE promotes activation of NF-kappa-B signaling (PubMed:39262777). Phosphorylation at Ser-358 is also required to activate IRF3 and may be specific for activation of NF-kappa-B signaling (PubMed:25636800, PubMed:40973797). Phosphorylation at Ser-355 by MAP3K7/TAK1 facilitates its interaction with STEEP1, promoting STING1 translocation to COPII vesicles (PubMed:37832545). Phosphorylation at Tyr-245 by EGFR promotes the activation of the cGAS-STING pathway and induction of type-I interferons, while inhibiting ability to promote autophagy (PubMed:32926474). Phosphorylated on tyrosine residues upon MHC-II aggregation (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:32753499, ECO:0000269|PubMed:32926474, ECO:0000269|PubMed:36261523, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:39262777, ECO:0000269|PubMed:40973797}.; PTM: Ubiquitinated (PubMed:19285439, PubMed:19433799, PubMed:21074459, PubMed:25254379, PubMed:41865946). 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 (By similarity). '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 (PubMed:21074459). 'Lys-63'-linked ubiquitination mediated by RNF115 and/or TRIM69 promotes homodimerization and activation (PubMed:33139700, PubMed:41865946). 'Lys-63'-linked ubiquitination at Lys-224 by MUL1 promotes activation of the cGAS-STING pathway without affecting activation of NF-kappa-B signaling (PubMed:28763789). 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation (PubMed:19285439). 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination (PubMed:25254379). 'Lys-27'- and 'Lys-29'-linked polyubiquitination at Lys-289 and Lys-370 mediated by TRIM10 promotes homooligomerization and activation (PubMed:36972172). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated by USP20; leading to its stabilization and promotion of innate antiviral response (PubMed:27801882). 'Lys-48'-linked deubiquitinated by USP44; leading to its stabilization and promotion of innate antiviral response (PubMed:31968013). Deubiquitinated by USP13; leading to inhibition of innate antiviral response (PubMed:28534493). 'Lys-63'-linked deubiquitinated by USP49; leading to inhibition of the subsequent recruitment of TBK1 to the signaling complex (PubMed:30943264). 'Lys-63'-linked ubiquitination mediated by RNF39 promotes the activation of the cGAS-STING pathway (PubMed:39255680). MARCHF5-mediated ubiquitination prevents the oxidation-induced polymer formation (PubMed:37916870). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:28763789, ECO:0000269|PubMed:30943264, ECO:0000269|PubMed:31968013, ECO:0000269|PubMed:33139700, ECO:0000269|PubMed:36972172, ECO:0000269|PubMed:37916870, ECO:0000269|PubMed:39255680, ECO:0000269|PubMed:41865946}.; PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to inhibition of cGAS-STING signaling. {ECO:0000269|PubMed:36802409}.; PTM: Sumoylated at Lys-338 by TRIM38 during the early phase of viral infection, promoting its stability by preventing its relocalization to autophagosomes and subsequent degradation. Desumoylated by SENP2 during the late phase of viral infection. {ECO:0000250|UniProtKB:Q3TBT3}.; PTM: ISGylated by HERC5, preventing ubiquitination and degradation. {ECO:0000269|PubMed:38652662}.; PTM: Alkylated via a non-enzymatic covalent modification (PubMed:36862550). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-148, preventing activity (By similarity). Also alkylated at Cys-91 by 4-octyl itaconate, a non-physiological metabolite, inhibiting palmitoylation, preventing STING1 activation (PubMed:36862550). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:36862550}.; PTM: (Microbial infection) DeISGylated by coronavirus SARS-CoV-2 papain-like protease nsp3, promoting ubiquitination and degradation. {ECO:0000269|PubMed:38652662}.; PTM: Palmitoylation takes place in the Golgi apparatus and creates a platform for the recruitment of TBK1 (PubMed:29973723, PubMed:40610719). Palmitoylation at Cys-64 enables subsequent STING1 oligomerization, ensuring proper conformation and subsequent downstream recruitment of TBK1 (PubMed:40610719). Palmitoylation at Cys-64 is also required to prevent inappropriate disulfide formation at Cys-148 in absence of cGAMP (PubMed:40610719). {ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:40610719}.; 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:0000269|PubMed:32541831}.
uniprot
proteins
protein_family
STING family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18724357
uniprot
proteins
pubmed
18818105
uniprot
proteins
pubmed
19285439
uniprot
proteins
pubmed
19416887
uniprot
proteins
pubmed
19433799
uniprot
proteins
pubmed
19776740
uniprot
proteins
pubmed
20628368
uniprot
proteins
pubmed
21074459
uniprot
proteins
pubmed
21947006
uniprot
proteins
pubmed
22394562
uniprot
proteins
pubmed
22579474
uniprot
proteins
pubmed
22705373
uniprot
proteins
pubmed
22728658
uniprot
proteins
pubmed
22728659
uniprot
proteins
pubmed
22728660
uniprot
proteins
pubmed
23027953
uniprot
proteins
pubmed
23258412
uniprot
proteins
pubmed
23707065
uniprot
proteins
pubmed
23722158
uniprot
proteins
pubmed
23747010
uniprot
proteins
pubmed
23910378
uniprot
proteins
pubmed
24077100
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25029335
uniprot
proteins
pubmed
25199835
uniprot
proteins
pubmed
25254379
uniprot
proteins
pubmed
25299331
uniprot
proteins
pubmed
25344812
uniprot
proteins
pubmed
25401470
uniprot
proteins
pubmed
25636800
uniprot
proteins
pubmed
25704810
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26150511
uniprot
proteins
pubmed
26229117
uniprot
proteins
pubmed
26300263
uniprot
proteins
pubmed
26405230
uniprot
proteins
pubmed
26669264
uniprot
proteins
pubmed
27302953
uniprot
proteins
pubmed
27801882
uniprot
proteins
pubmed
28331227
uniprot
proteins
pubmed
28534493
uniprot
proteins
pubmed
28763789
uniprot
proteins
pubmed
29038422
uniprot
proteins
pubmed
29251827
uniprot
proteins
pubmed
29478775
uniprot
proteins
pubmed
29694889
uniprot
proteins
pubmed
29973723
uniprot
proteins
pubmed
30045990
uniprot
proteins
pubmed
30104205
uniprot
proteins
pubmed
30568238
uniprot
proteins
pubmed
30643259
uniprot
proteins
pubmed
30655953
uniprot
proteins
pubmed
30842653
uniprot
proteins
pubmed
30842659
uniprot
proteins
pubmed
30842662
uniprot
proteins
pubmed
30943264
uniprot
proteins
pubmed
31107917
uniprot
proteins
pubmed
31230712
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
31659299
uniprot
proteins
pubmed
31968013
uniprot
proteins
pubmed
31992625
uniprot
proteins
pubmed
32238587
uniprot
proteins
pubmed
32268090
uniprot
proteins
pubmed
32541831
uniprot
proteins
pubmed
32690950
uniprot
proteins
pubmed
32753499
uniprot
proteins
pubmed
32926474
uniprot
proteins
pubmed
32929276
uniprot
proteins
pubmed
33057424
uniprot
proteins
pubmed
33139700
uniprot
proteins
pubmed
33162473
uniprot
proteins
pubmed
34903048
uniprot
proteins
pubmed
35013224
uniprot
proteins
pubmed
35045565
uniprot
proteins
pubmed
35388221
uniprot
proteins
pubmed
35556195
uniprot
proteins
pubmed
36261523
uniprot
proteins
pubmed
36802409
uniprot
proteins
pubmed
36808561
uniprot
proteins
pubmed
36862550
uniprot
proteins
pubmed
36972172
uniprot
proteins
pubmed
37086726
uniprot
proteins
pubmed
37379839
uniprot
proteins
pubmed
37535724
uniprot
proteins
pubmed
37828400
uniprot
proteins
pubmed
37832545
uniprot
proteins
pubmed
37916870
uniprot
proteins
pubmed
38652662
uniprot
proteins
pubmed
38917796
uniprot
proteins
pubmed
39255680
uniprot
proteins
pubmed
39262777
uniprot
proteins
pubmed
39423796
uniprot
proteins
pubmed
39689715
uniprot
proteins
pubmed
39947179
uniprot
proteins
pubmed
40498864
uniprot
proteins
pubmed
40610719
uniprot
proteins
pubmed
40973797
uniprot
proteins
pubmed
41639452
uniprot
proteins
pubmed
41639454
uniprot
proteins
pubmed
41747053
uniprot
proteins
pubmed
41865946
uniprot
proteins
pubmed
41887218
uniprot
proteins
sequence_length
379
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate compartment membrane {ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454, ECO:0000269|PubMed:41887218}; Multi-pass membrane protein {ECO:0000255, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:41639452}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:25254379, ECO:0000269|PubMed:29694889, ECO:0000269|PubMed:30643259, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:40498864, ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454}; Multi-pass membrane protein {ECO:0000255, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:32690950}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:29694889, ECO:0000269|PubMed:30842653}. Golgi apparatus membrane {ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:34903048, ECO:0000269|PubMed:36808561, ECO:0000269|PubMed:36972172, ECO:0000269|PubMed:37535724}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:39947179}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:30842662}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:29694889, ECO:0000269|PubMed:36261523, ECO:0000305|PubMed:40973797}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:36261523, ECO:0000305|PubMed:40973797}; Multi-pass membrane protein {ECO:0000255}. Mitochondrion outer membrane {ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:19285439, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q3TBT3}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to the endoplasmic reticulum when inactive (PubMed:19433799, PubMed:29694889, PubMed:30842653, PubMed:30842659). 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 (PubMed:19433799, PubMed:29694889, PubMed:30842653, PubMed:30842659, PubMed:37832545). 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 (PubMed:41639452, PubMed:41639454). STING1-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis (PubMed:30842662). Activates NF-kappa-B signaling when localized to the endolysosome compartment (PubMed:40973797). Localizes in the lysosome membrane in a TMEM203-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:29694889, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:40973797, ECO:0000269|PubMed:41639452, ECO:0000269|PubMed:41639454}.
uniprot
proteins
transmembrane_region
TRANSMEM 18..34; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:30842659"; TRANSMEM 45..69; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:30842659"; TRANSMEM 92..106; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:30842659"; TRANSMEM 117..134; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:30842659
uniprot
proteins