STING1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0045087 innate immune response	IBA GO_REF:0000033	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0016239 positive regulation of macroautophagy	IBA GO_REF:0000033	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0061507 2',3'-cyclic GMP-AMP binding	IBA GO_REF:0000033	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0002218 activation of innate immune response	IBA GO_REF:0000033	ACCEPT	Summary: Ligand-bound STING1 activates the innate immune response rather than merely participating in it. Reason: Correct and consistent with the experimental and phylogenetic evidence; kept as-is.
GO:0051607 defense response to virus	IBA GO_REF:0000033	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0032481 positive regulation of type I interferon production	IBA GO_REF:0000033	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0000045 autophagosome assembly	IBA GO_REF:0000033	ACCEPT	Summary: STING1-containing ERGIC membrane serves as the source for LC3 lipidation and autophagosome biogenesis. Reason: Supported by three independent IDA rows plus an IBA, and mechanistically explained: the process is independent of TBK1 and of interferon induction, so it is a real second function rather than a downstream effect of interferon. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0005776 autophagosome	IBA GO_REF:0000033	ACCEPT	Summary: STING1 is found on autophagosomes formed from STING-containing ERGIC membrane. Reason: Consistent with the autophagy-related process annotations and with the ERGIC-as-membrane-source mechanism. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0035438 cyclic-di-GMP binding	IBA GO_REF:0000033	ACCEPT	Summary: STING1 binds bacterial cyclic di-GMP directly, acting as a sensor for bacterial cyclic dinucleotides as well as for host cGAMP. Reason: Core molecular function. Direct radioligand binding with competition by unlabelled cyclic dinucleotides but not by other nucleotides, plus mutations that selectively impair the cyclic-dinucleotide response. This is the activity that grounds the antibacterial innate immune annotations. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0061709 reticulophagy	IBA GO_REF:0000033	ACCEPT	Summary: Cyclic-di-GMP-triggered STING1 signalling has been linked to selective autophagy of the ER. Reason: The weakest member of the autophagy cluster: UniProt supports it only "By similarity", and the human evidence is IBA/IEA/ISS with no direct experimental row. Kept as-is rather than downgraded because doing so would require asserting a propagation failure in the PANTHER family (PTN005046674) that I did not inspect, and because ER-derived membrane is genuinely the source of STING-induced autophagosomes. Flagged here as the annotation on this gene I would most like to see experimentally confirmed or retired.
GO:0000139 Golgi membrane	IEA GO_REF:0000120	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0000421 autophagosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: The membrane of the autophagosome is the correct component for a polytopic membrane protein found on autophagosomes. Reason: More precise counterpart of the autophagosome annotation; consistent with UniProt's curated location.
GO:0002218 activation of innate immune response	IEA GO_REF:0000120	ACCEPT	Summary: Ligand-bound STING1 activates the innate immune response rather than merely participating in it. Reason: Correct and consistent with the experimental and phylogenetic evidence; kept as-is.
GO:0005741 mitochondrial outer membrane	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0005765 lysosomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: STING1 is delivered to lysosomal membranes, where the signal is terminated by degradation. Reason: Correct; the lysosome is the endpoint of the activated protein's route and the site at which signalling is resolved.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005794 Golgi apparatus	IEA GO_REF:0000120	MODIFY	Summary: STING1 sits in the Golgi membrane rather than in the Golgi apparatus generally. Reason: Correct but under-specific for a multi-pass membrane protein; GO:0000139 is already annotated with experimental support. Proposed replacements: Golgi membrane
GO:0005886 plasma membrane	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Plasma membrane localisation has no human experimental support and is contradicted by the trafficking literature. Reason: The three rows are IEA from UniProt subcellular-location mapping, ISS, and a generic Reactome exocytosis reaction; UniProt itself qualifies "Cell membrane" as ECO:0000250 by similarity to mouse Q3TBT3. The 2026 lipid work states positively that activated STING1 traffics to the Golgi and Golgi-derived endosomes but not to the plasma membrane. Marked as over-annotation rather than removed because the ISS is a curator judgement about the mouse orthologue. Supporting Evidence: PMID:41639452 PI(4,5)P2 is enriched in the plasma membrane, but also present in the Golgi and endosomes at much lower levels35,37. PI(3,5)P2 is mostly localized to late endosomes and lysosomes35. Upon cGAMP binding, STING traffics to Golgi and Golgi-derived endosomes, but not plasma membrane.
GO:0010008 endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: STING1 resides in endosomal membranes late in its itinerary. Reason: Correct and appropriately specific for a multi-pass membrane protein.
GO:0032481 positive regulation of type I interferon production	IEA GO_REF:0000120	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IEA GO_REF:0000120	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Activated STING1 accumulates in perinuclear vesicle clusters, and this clustering is required for TBK1 activation. Reason: Correct and functionally meaningful rather than incidental: perinuclear clustering is the step at which high-order oligomers support TBK1 trans-autophosphorylation. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: The biological-process counterpart of the proton channel molecular function. Reason: Consistent with the accepted GO:0015252 annotation: STING1 mediates proton efflux from the Golgi lumen. Electronic (GO_REF:0000108) but correct, and grounded in liposome reconstitution of the purified protein. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. PMID:39947179 Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus.
GO:0005515 protein binding	IPI PMID:18724357 STING is an endoplasmic reticulum adaptor that facilitates i...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:19416887 ISG56 is a negative-feedback regulator of virus-triggered si...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:20080758 WDR5 is essential for assembly of the VISA-associated signal...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:20890285 IFI16 is an innate immune sensor for intracellular DNA.	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:22000020 Activation of STAT6 by STING is critical for antiviral innat...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:22312431 Coronavirus papain-like proteases negatively regulate antivi...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:22911572 Hepatitis C virus NS4B protein targets STING and abrogates R...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:23542348 Hepatitis C virus NS4B blocks the interaction of STING and T...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:26405230 DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sens...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:29251827 Quantitative Proteomics Identified TTC4 as a TBK1 Interactor...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0042802 identical protein binding	IPI PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:22312431 Coronavirus papain-like proteases negatively regulate antivi...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:22728658 Structure of STING bound to cyclic di-GMP reveals the mechan...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:22728659 The structural basis for the sensing and binding of cyclic d...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:22728660 Crystal structures of STING protein reveal basis for recogni...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:23542348 Hepatitis C virus NS4B blocks the interaction of STING and T...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:30405246 Design of amidobenzimidazole STING receptor agonists with sy...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0042802 identical protein binding	IPI PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	MODIFY	Summary: These IPI rows record STING1 binding to itself; the specific homodimerisation term is available and is already annotated on this gene. Reason: Correct but under-specific. "Identical protein binding" is the generic parent; GO:0042803 protein homodimerization activity states the same fact informatively and is supported by the structural work. Proposed replacements: protein homodimerization activity
GO:0000045 autophagosome assembly	IEA GO_REF:0000107	ACCEPT	Summary: STING1-containing ERGIC membrane serves as the source for LC3 lipidation and autophagosome biogenesis. Reason: Supported by three independent IDA rows plus an IBA, and mechanistically explained: the process is independent of TBK1 and of interferon induction, so it is a real second function rather than a downstream effect of interferon. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0005737 cytoplasm	IEA GO_REF:0000107	MODIFY	Summary: Cytoplasm is uninformative for a polytopic membrane protein with a defined organellar itinerary. Reason: Correct but maximally general, and it arrives by orthology transfer. The ER membrane is the location this gene is actually characterised in. Proposed replacements: endoplasmic reticulum membrane
GO:0005776 autophagosome	IEA GO_REF:0000107	ACCEPT	Summary: STING1 is found on autophagosomes formed from STING-containing ERGIC membrane. Reason: Consistent with the autophagy-related process annotations and with the ERGIC-as-membrane-source mechanism. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0005777 peroxisome	IEA GO_REF:0000107	REMOVE	Summary: STING1 is not a peroxisomal protein. Reason: The single row is IEA by Ensembl Compara orthology transfer from mouse (GO_REF:0000107, WITH UniProtKB:Q3TBT3\|ensembl:ENSMUSP00000111393). Human UniProt lists ERGIC, ER, perinuclear cytoplasm, Golgi, trans-Golgi network, autophagosome, endosome, lysosome, mitochondrion outer membrane and cell membrane as locations - peroxisome is absent - and no primary study places STING1 in peroxisomes. This is a demonstrably wrong electronic inference, the case where removal is appropriate.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000107	MODIFY	Summary: STING1 is not a soluble ER lumenal or ER-associated protein; it is integral to the ER membrane. Reason: Correct but under-specific; the gene already carries GO:0005789 with extensive experimental support. Proposed replacements: endoplasmic reticulum membrane
GO:0015252 proton channel activity	IEA GO_REF:0000107	ACCEPT	Summary: STING1 is a proton channel: its transmembrane domain conducts protons and deacidifies the Golgi, driving an output branch that is separable from interferon induction. Reason: Scrutinised because a proton channel is a non-obvious assignment for an ER adaptor, and it holds. The founding study reconstituted purified STING into liposomes and measured transmembrane proton transport, with the agonist C53 (which binds the channel interface) blocking flux - so the conductance is a property of the protein, not an indirect cellular readout. It has since been used and required by at least three further independent laboratories (Tan lab, PMID:39423796; Miner lab, PMID:39947179; Yan lab, PMID:40185098) and the channel has become a small-molecule binding site. No refutation was found on PubMed search. Treated as a second core molecular function, distinct from the adaptor activity. Note the contrast with TMEM175, where the proton-channel claim genuinely is contested; here it is not. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes. PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel. PMID:39947179 Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus. PMID:40185098 This process requires STING's proton channel function, the V-ATPase-ATG5-ATG8 cascade, and is independent of immune signaling. PMID:42336656 The allosteric binding site lies within a hydrophobic transmembrane proton channel formed by intertwined helices of two STING monomers.
GO:0016239 positive regulation of macroautophagy	IEA GO_REF:0000107	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: STING1 is bound by several E3 ubiquitin ligases (RNF5, TRIM56, RNF26, TRIM69) that tune its stability and activity. Reason: Real but regulatory and peripheral: these are interactions STING1 is subject to rather than an activity it performs to execute its function. Electronic (IEA) assignment; kept, not promoted.
GO:0032728 positive regulation of interferon-beta production	IEA GO_REF:0000107	ACCEPT	Summary: IFN-beta is the principal type I interferon induced downstream of STING1. Reason: Correct and more specific than the parent type I interferon term; retained alongside it. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0035438 cyclic-di-GMP binding	IEA GO_REF:0000107	ACCEPT	Summary: STING1 binds bacterial cyclic di-GMP directly, acting as a sensor for bacterial cyclic dinucleotides as well as for host cGAMP. Reason: Core molecular function. Direct radioligand binding with competition by unlabelled cyclic dinucleotides but not by other nucleotides, plus mutations that selectively impair the cyclic-dinucleotide response. This is the activity that grounds the antibacterial innate immune annotations. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IEA GO_REF:0000107	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0045087 innate immune response	IEA GO_REF:0000107	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0051607 defense response to virus	IEA GO_REF:0000107	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0060340 positive regulation of type I interferon-mediated signaling pathway	IEA GO_REF:0000107	MODIFY	Summary: STING1 drives interferon production; it does not act within the interferon receptor signalling pathway. Reason: Category confusion between production and response. The experiments underlying these rows measure induction of interferon and interferon-stimulated genes downstream of STING1 activation, which is GO:0032481, a term the gene already carries from ten other references. Proposed replacements: positive regulation of type I interferon production
GO:0061507 2',3'-cyclic GMP-AMP binding	IEA GO_REF:0000120	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0061709 reticulophagy	IEA GO_REF:0000107	ACCEPT	Summary: Cyclic-di-GMP-triggered STING1 signalling has been linked to selective autophagy of the ER. Reason: The weakest member of the autophagy cluster: UniProt supports it only "By similarity", and the human evidence is IBA/IEA/ISS with no direct experimental row. Kept as-is rather than downgraded because doing so would require asserting a propagation failure in the PANTHER family (PTN005046674) that I did not inspect, and because ER-derived membrane is genuinely the source of STING-induced autophagosomes. Flagged here as the annotation on this gene I would most like to see experimentally confirmed or retired.
GO:0140896 cGAS/STING signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:1904262 negative regulation of TORC1 signaling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: STING1 activation sequesters the FLCN-FNIP complex and relieves mTORC1-dependent inhibition of TFEB and TFE3. Reason: Real and mechanistically specific, from two independent 2024-2025 studies, but it is a step within the lysosome-biogenesis branch rather than a function of STING1 in its own right. Non-core. Supporting Evidence: PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel.
GO:1905673 positive regulation of lysosome organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Through TFEB/TFE3 activation, STING1 drives expression of lysosomal genes and lysosome biogenesis. Reason: A genuine, TBK1-independent branch of STING1 biology, downstream of the proton channel activity. Kept as non-core because it is an output of the channel function rather than a defining role of the protein. Supporting Evidence: PMID:39423796 STING stimulates global upregulation of TFEB-target genes, mediating lysosomal biogenesis and autophagy.
GO:1990231 STING complex	IEA GO_REF:0000107	ACCEPT	Summary: STING1 is the defining component of the STING complex. Reason: Correct and specific; supported by IPI and consistent with the homodimer/oligomer structural literature.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:38917796 PELI2 is a negative regulator of STING signaling that is dyn...	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:38917796 PELI2 is a negative regulator of STING signaling that is dyn...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0035591 signaling adaptor activity	IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN...	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:31659299 HIV-2/SIV Vpx targets a novel functional domain of STING to ...	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:28763789 Ubiquitination of STING at lysine 224 controls IRF3 activati...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0016239 positive regulation of macroautophagy	IDA PMID:32926474 EGFR-mediated tyrosine phosphorylation of STING determines i...	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0035591 signaling adaptor activity	IDA PMID:37086726 The mechanism of STING autoinhibition and activation.	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:37086726 The mechanism of STING autoinhibition and activation.	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:32926474 EGFR-mediated tyrosine phosphorylation of STING determines i...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0140896 cGAS/STING signaling pathway	IDA PMID:37086726 The mechanism of STING autoinhibition and activation.	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0015252 proton channel activity	IDA PMID:39423796 A TBK1-independent primordial function of STING in lysosomal...	ACCEPT	Summary: STING1 is a proton channel: its transmembrane domain conducts protons and deacidifies the Golgi, driving an output branch that is separable from interferon induction. Reason: Scrutinised because a proton channel is a non-obvious assignment for an ER adaptor, and it holds. The founding study reconstituted purified STING into liposomes and measured transmembrane proton transport, with the agonist C53 (which binds the channel interface) blocking flux - so the conductance is a property of the protein, not an indirect cellular readout. It has since been used and required by at least three further independent laboratories (Tan lab, PMID:39423796; Miner lab, PMID:39947179; Yan lab, PMID:40185098) and the channel has become a small-molecule binding site. No refutation was found on PubMed search. Treated as a second core molecular function, distinct from the adaptor activity. Note the contrast with TMEM175, where the proton-channel claim genuinely is contested; here it is not. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes. PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel. PMID:39947179 Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus. PMID:40185098 This process requires STING's proton channel function, the V-ATPase-ATG5-ATG8 cascade, and is independent of immune signaling. PMID:42336656 The allosteric binding site lies within a hydrophobic transmembrane proton channel formed by intertwined helices of two STING monomers.
GO:1904262 negative regulation of TORC1 signaling	IDA PMID:39423796 A TBK1-independent primordial function of STING in lysosomal...	KEEP AS NON CORE	Summary: STING1 activation sequesters the FLCN-FNIP complex and relieves mTORC1-dependent inhibition of TFEB and TFE3. Reason: Real and mechanistically specific, from two independent 2024-2025 studies, but it is a step within the lysosome-biogenesis branch rather than a function of STING1 in its own right. Non-core. Supporting Evidence: PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel.
GO:1904262 negative regulation of TORC1 signaling	IDA PMID:39689715 The cGAS-STING pathway activates transcription factor TFEB t...	KEEP AS NON CORE	Summary: STING1 activation sequesters the FLCN-FNIP complex and relieves mTORC1-dependent inhibition of TFEB and TFE3. Reason: Real and mechanistically specific, from two independent 2024-2025 studies, but it is a step within the lysosome-biogenesis branch rather than a function of STING1 in its own right. Non-core. Supporting Evidence: PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel.
GO:1905673 positive regulation of lysosome organization	IDA PMID:39423796 A TBK1-independent primordial function of STING in lysosomal...	KEEP AS NON CORE	Summary: Through TFEB/TFE3 activation, STING1 drives expression of lysosomal genes and lysosome biogenesis. Reason: A genuine, TBK1-independent branch of STING1 biology, downstream of the proton channel activity. Kept as non-core because it is an output of the channel function rather than a defining role of the protein. Supporting Evidence: PMID:39423796 STING stimulates global upregulation of TFEB-target genes, mediating lysosomal biogenesis and autophagy.
GO:1905673 positive regulation of lysosome organization	IDA PMID:39689715 The cGAS-STING pathway activates transcription factor TFEB t...	KEEP AS NON CORE	Summary: Through TFEB/TFE3 activation, STING1 drives expression of lysosomal genes and lysosome biogenesis. Reason: A genuine, TBK1-independent branch of STING1 biology, downstream of the proton channel activity. Kept as non-core because it is an output of the channel function rather than a defining role of the protein. Supporting Evidence: PMID:39423796 STING stimulates global upregulation of TFEB-target genes, mediating lysosomal biogenesis and autophagy.
GO:0000139 Golgi membrane	IDA PMID:37535724 Human STING is a proton channel.	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0001819 positive regulation of cytokine production	IDA PMID:39947179 ArfGAP2 promotes STING proton channel activity, cytokine tra...	KEEP AS NON CORE	Summary: STING1 proton-channel activity non-transcriptionally promotes Golgi transit and secretion of cytokines and chemokines. Reason: Correct and interesting - it is regulation of cytokine output at the level of trafficking rather than transcription - but general. The specific transcriptional terms (GO:0032481, GO:0032728) carry the core claim; this is retained as non-core. Supporting Evidence: PMID:39947179 Deletion of ArfGAP2 in hematopoietic and endothelial cells markedly reduces STING-mediated cytokine and chemokine secretion, immune cell activation, and autoinflammatory pathology in SAVI mice.
GO:0015252 proton channel activity	IDA PMID:39947179 ArfGAP2 promotes STING proton channel activity, cytokine tra...	ACCEPT	Summary: STING1 is a proton channel: its transmembrane domain conducts protons and deacidifies the Golgi, driving an output branch that is separable from interferon induction. Reason: Scrutinised because a proton channel is a non-obvious assignment for an ER adaptor, and it holds. The founding study reconstituted purified STING into liposomes and measured transmembrane proton transport, with the agonist C53 (which binds the channel interface) blocking flux - so the conductance is a property of the protein, not an indirect cellular readout. It has since been used and required by at least three further independent laboratories (Tan lab, PMID:39423796; Miner lab, PMID:39947179; Yan lab, PMID:40185098) and the channel has become a small-molecule binding site. No refutation was found on PubMed search. Treated as a second core molecular function, distinct from the adaptor activity. Note the contrast with TMEM175, where the proton-channel claim genuinely is contested; here it is not. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes. PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel. PMID:39947179 Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus. PMID:40185098 This process requires STING's proton channel function, the V-ATPase-ATG5-ATG8 cascade, and is independent of immune signaling. PMID:42336656 The allosteric binding site lies within a hydrophobic transmembrane proton channel formed by intertwined helices of two STING monomers.
GO:0032588 trans-Golgi network membrane	IDA PMID:39947179 ArfGAP2 promotes STING proton channel activity, cytokine tra...	ACCEPT	Summary: STING1 reaches the trans-Golgi network during its post-activation itinerary. Reason: Specific and experimentally supported; consistent with the Golgi membrane annotation.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:41887218 STING signaling modulation by COPII cargo recognition.	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0035591 signaling adaptor activity	IDA PMID:40973797 STING signals to NF-κB from late endolysosomal compartments ...	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0035591 signaling adaptor activity	IDA PMID:41747053 STING-NF-κB signaling builds an influenza spillover barrier.	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0036020 endolysosome membrane	IDA PMID:40973797 STING signals to NF-κB from late endolysosomal compartments ...	ACCEPT	Summary: STING1 signals to NF-kB from late endolysosomal compartments after Golgi exit. Reason: Recently established and mechanistically specific: the NF-kB branch is licensed only in this compartment, between Golgi exit and lysosomal degradation. Supporting Evidence: PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:32268090 TBK1 and IKKε Act Redundantly to Mediate STING-Induced NF-κB...	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:39262777 IKKɛ induces STING non-IFN immune responses via a mechanism ...	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:40973797 STING signals to NF-κB from late endolysosomal compartments ...	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IDA PMID:41747053 STING-NF-κB signaling builds an influenza spillover barrier.	ACCEPT	Summary: STING1 activates canonical NF-kB signalling as a genuine second transcriptional output, separable from the interferon arm. Reason: Core biological process. Seven independent experimental rows, and recent work localises this branch to post-Golgi endolysosomal compartments and shows it can operate independently of type I interferon signalling - so it is not simply a downstream consequence of interferon induction. Supporting Evidence: PMID:40973797 Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. PMID:40973797 IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB.
GO:0051607 defense response to virus	IDA PMID:41747053 STING-NF-κB signaling builds an influenza spillover barrier.	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0140374 antiviral innate immune response	IDA PMID:41747053 STING-NF-κB signaling builds an influenza spillover barrier.	ACCEPT	Summary: The antiviral arm of the innate response is the best-characterised output of STING1 signalling. Reason: Correct and more informative than the generic defense-response term; three independent IDA rows.
GO:0042803 protein homodimerization activity	IDA PMID:31230712 STING Polymer Structure Reveals Mechanisms for Activation, H...	ACCEPT	Summary: STING1 is an obligate homodimer, and cGAMP-induced side-by-side packing of dimers into tetramers and higher-order oligomers is the activation mechanism. Reason: Well supported by multiple independent crystal and cryo-EM structures as well as biochemistry. Retained as a genuine molecular function because oligomerisation state, not just ligand occupancy, is what licenses ER exit and TBK1 activation. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0042803 protein homodimerization activity	IDA PMID:41865946 TRIM69 potentiates the cGAS-STING signalling pathway by prom...	ACCEPT	Summary: STING1 is an obligate homodimer, and cGAMP-induced side-by-side packing of dimers into tetramers and higher-order oligomers is the activation mechanism. Reason: Well supported by multiple independent crystal and cryo-EM structures as well as biochemistry. Retained as a genuine molecular function because oligomerisation state, not just ligand occupancy, is what licenses ER exit and TBK1 activation. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0140374 antiviral innate immune response	IDA PMID:38421872 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate ...	ACCEPT	Summary: The antiviral arm of the innate response is the best-characterised output of STING1 signalling. Reason: Correct and more informative than the generic defense-response term; three independent IDA rows.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:31230712 STING Polymer Structure Reveals Mechanisms for Activation, H...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0140896 cGAS/STING signaling pathway	IDA PMID:41865946 TRIM69 potentiates the cGAS-STING signalling pathway by prom...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0035438 cyclic-di-GMP binding	IDA PMID:21947006 STING is a direct innate immune sensor of cyclic di-GMP.	ACCEPT	Summary: STING1 binds bacterial cyclic di-GMP directly, acting as a sensor for bacterial cyclic dinucleotides as well as for host cGAMP. Reason: Core molecular function. Direct radioligand binding with competition by unlabelled cyclic dinucleotides but not by other nucleotides, plus mutations that selectively impair the cyclic-dinucleotide response. This is the activity that grounds the antibacterial innate immune annotations. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0140367 antibacterial innate immune response	IDA PMID:21813773 IFN-induced TPR protein IFIT3 potentiates antiviral signalin...	ACCEPT	Summary: Direct binding of bacterial cyclic di-GMP makes STING1 a sensor in antibacterial innate immunity, not only an antiviral adaptor. Reason: Grounded in the same experiments that establish cyclic-di-GMP binding; four independent IDA rows. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0140367 antibacterial innate immune response	IDA PMID:21947006 STING is a direct innate immune sensor of cyclic di-GMP.	ACCEPT	Summary: Direct binding of bacterial cyclic di-GMP makes STING1 a sensor in antibacterial innate immunity, not only an antiviral adaptor. Reason: Grounded in the same experiments that establish cyclic-di-GMP binding; four independent IDA rows. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0140367 antibacterial innate immune response	IDA PMID:22705373 Cyclic di-GMP sensing via the innate immune signaling protei...	ACCEPT	Summary: Direct binding of bacterial cyclic di-GMP makes STING1 a sensor in antibacterial innate immunity, not only an antiviral adaptor. Reason: Grounded in the same experiments that establish cyclic-di-GMP binding; four independent IDA rows. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0140367 antibacterial innate immune response	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	ACCEPT	Summary: Direct binding of bacterial cyclic di-GMP makes STING1 a sensor in antibacterial innate immunity, not only an antiviral adaptor. Reason: Grounded in the same experiments that establish cyclic-di-GMP binding; four independent IDA rows. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0070972 protein localization to endoplasmic reticulum	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	MARK AS OVER ANNOTATED	Summary: The underlying experiment concerns STING1's own regulated exit from the ER, not STING1 acting to localise other proteins to the ER. Reason: The paper identifies TAK1-mediated phosphorylation of STING1 Ser355 as a checkpoint for its trafficking to the ERGIC. That is a fact about STING1's own subcellular itinerary, which GO captures as cellular component (GO:0005789, GO:0033116), not as an involved_in protein-localization process. Not removed - it is an IDA and the observation is real - but flagged as a mis-fitted term. Supporting Evidence: PMID:37832545 activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	IDA PMID:41639454 PtdIns(3,5)P(2) is an endogenous ligand of STING in innate i...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0015485 cholesterol binding	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	ACCEPT	Summary: STING1 binds cholesterol at the same dimer-dimer interface that binds phosphoinositide, and the two lipids act cooperatively to stabilise the oligomer. Reason: Interesting alongside the companion phosphoinositide paper, and consistent with it rather than duplicating it: cholesterol and PtdInsP occupy adjacent positions in the cryo-EM maps, the S80I and W82Q mutants selectively lose cholesterol binding and lose cGAMP-induced phosphorylation of STING, TBK1 and IRF3, and a cholesterol-like density was present at the same site in the authors' earlier PIP-free structure. Unlike the phosphoinositide claim, a role for cholesterol in STING activation had been reported by other groups beforehand, which strengthens it. Same single-programme caveat applies to the direct-binding demonstration itself. Supporting Evidence: PMID:41639452 Our results show that STING wild type (WT) binds to most PIP lipids, cholesterol and its derivatives, but not several other types of lipids such as non-phosphorylated phosphatidylinositol (PI), phosphatidylethanolamine (PE) and phosphatidylserine (PS). PMID:41639452 Our cell-based functional assay revealed that mutations to residues involved in the interactions with PIPs and cholesterol, including R71H, K20E/R71H, S80I and W82Q, substantially reduced phosphorylation of STING, TBK1 and IRF3 triggered by cGAMP PMID:41639452 supporting previous studies that cholesterol plays a role in STING activation and regulation
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:41639454 PtdIns(3,5)P(2) is an endogenous ligand of STING in innate i...	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	ACCEPT	Summary: STING1 binds PtdIns(3,5)P2 directly through a groove in its transmembrane region; the lipid acts as a molecular glue that, together with cGAMP, drives high-order oligomerisation and ER exit. Reason: This is the newly assigned molecular function of the gene and GOA already carries it as IDA from both 2026 Nature papers. Weighing the evidence honestly: the two papers are co-submitted companions with overlapping authorship (the cryo-EM structure cited by Tan et al. IS the Li et al. paper), so they are corroboration within one research programme, not independent replication, and no second laboratory has yet reproduced the direct binding. It is nonetheless accepted because (i) the support is multi-modal rather than one assay - FRET with labelled lipid against full-length protein, lipid strips, cryo-EM density at a defined dimer-dimer groove, structure-guided K20E/R71H loss of binding and of signalling, liposome reconstitution, and PIKFYVE deletion phenocopying the binding mutant; (ii) it converges on pre-existing independent human genetics, since R71 is part of the common hypofunctional HAQ allele and the structure explains why; and (iii) a modulatory role for phosphoinositides and cholesterol in STING activation had already been reported by other groups, which these papers set out to explain mechanistically. Recorded as a core-adjacent activation requirement rather than a third output branch. Supporting Evidence: PMID:41639454 These results indicate that STING directly binds to PtdIns(3,5)P2. PMID:41639454 PtdIns(3,5)P2 bound directly to STING in fluorescence resonance energy transfer assays. PMID:41639454 Proteomic analyses identified a constitutive interaction between STING and PIKFYVE, an enzyme that produces PtdIns(3,5)P2 in mammalian cells. Deletion of PIKFYVE blocked STING trafficking from the ER and TBK1 activation. PMID:41639452 Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 and PtdIns(4,5)P2, and by PtdIns4P to a lesser extent. PMID:41639452 Our cryo-electron microscopy structures reveal that PtdInsPs together with cholesterol bind at the interface between STING dimers, directly promoting the high-order oligomerization. PMID:41639452 Our cryo-EM results show that R71 forms a salt bridge with the 5-phosphate group of PI(3,5)P2 or PI(4,5)P2, which provides a structural explanation for its critical role in STING activation.
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding	IDA PMID:41639454 PtdIns(3,5)P(2) is an endogenous ligand of STING in innate i...	ACCEPT	Summary: STING1 binds PtdIns(3,5)P2 directly through a groove in its transmembrane region; the lipid acts as a molecular glue that, together with cGAMP, drives high-order oligomerisation and ER exit. Reason: This is the newly assigned molecular function of the gene and GOA already carries it as IDA from both 2026 Nature papers. Weighing the evidence honestly: the two papers are co-submitted companions with overlapping authorship (the cryo-EM structure cited by Tan et al. IS the Li et al. paper), so they are corroboration within one research programme, not independent replication, and no second laboratory has yet reproduced the direct binding. It is nonetheless accepted because (i) the support is multi-modal rather than one assay - FRET with labelled lipid against full-length protein, lipid strips, cryo-EM density at a defined dimer-dimer groove, structure-guided K20E/R71H loss of binding and of signalling, liposome reconstitution, and PIKFYVE deletion phenocopying the binding mutant; (ii) it converges on pre-existing independent human genetics, since R71 is part of the common hypofunctional HAQ allele and the structure explains why; and (iii) a modulatory role for phosphoinositides and cholesterol in STING activation had already been reported by other groups, which these papers set out to explain mechanistically. Recorded as a core-adjacent activation requirement rather than a third output branch. Supporting Evidence: PMID:41639454 These results indicate that STING directly binds to PtdIns(3,5)P2. PMID:41639454 PtdIns(3,5)P2 bound directly to STING in fluorescence resonance energy transfer assays. PMID:41639454 Proteomic analyses identified a constitutive interaction between STING and PIKFYVE, an enzyme that produces PtdIns(3,5)P2 in mammalian cells. Deletion of PIKFYVE blocked STING trafficking from the ER and TBK1 activation. PMID:41639452 Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 and PtdIns(4,5)P2, and by PtdIns4P to a lesser extent. PMID:41639452 Our cryo-electron microscopy structures reveal that PtdInsPs together with cholesterol bind at the interface between STING dimers, directly promoting the high-order oligomerization. PMID:41639452 Our cryo-EM results show that R71 forms a salt bridge with the 5-phosphate group of PI(3,5)P2 or PI(4,5)P2, which provides a structural explanation for its critical role in STING activation.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0140896 cGAS/STING signaling pathway	IDA PMID:41639454 PtdIns(3,5)P(2) is an endogenous ligand of STING in innate i...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN...	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0005829 cytosol	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: STING1 is an integral membrane protein; only its C-terminal ligand-binding and signalling domain faces the cytosol. Reason: The rows are an HPA-derived IDA and a Reactome TAS. Cytosol as a location misrepresents the topology of a four-transmembrane protein, though the cytosol-facing domain explains why the signal arises. Supporting Evidence: PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005515 protein binding	IPI PMID:30540941 TMED2 Potentiates Cellular IFN Responses to DNA Viruses by R...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0000139 Golgi membrane	EXP PMID:30842653 Structural basis of STING binding with and phosphorylation b...	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0000139 Golgi membrane	EXP PMID:34903048 Human Cytomegalovirus UL138 Protein Inhibits the STING Pathw...	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0000139 Golgi membrane	EXP PMID:36808561 Varicella-Zoster Virus ORF39 Transmembrane Protein Suppresse...	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0005741 mitochondrial outer membrane	EXP PMID:18724357 STING is an endoplasmic reticulum adaptor that facilitates i...	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0005741 mitochondrial outer membrane	EXP PMID:19285439 The ubiquitin ligase RNF5 regulates antiviral responses by m...	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0005741 mitochondrial outer membrane	EXP PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0005741 mitochondrial outer membrane	EXP PMID:19776740 STING regulates intracellular DNA-mediated, type I interfero...	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0005789 endoplasmic reticulum membrane	EXP PMID:18724357 STING is an endoplasmic reticulum adaptor that facilitates i...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	EXP PMID:19285439 The ubiquitin ligase RNF5 regulates antiviral responses by m...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	EXP PMID:19776740 STING regulates intracellular DNA-mediated, type I interfero...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	EXP PMID:30842653 Structural basis of STING binding with and phosphorylation b...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	EXP PMID:32690950 STEEP mediates STING ER exit and activation of signaling.	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005886 plasma membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Plasma membrane localisation has no human experimental support and is contradicted by the trafficking literature. Reason: The three rows are IEA from UniProt subcellular-location mapping, ISS, and a generic Reactome exocytosis reaction; UniProt itself qualifies "Cell membrane" as ECO:0000250 by similarity to mouse Q3TBT3. The 2026 lipid work states positively that activated STING1 traffics to the Golgi and Golgi-derived endosomes but not to the plasma membrane. Marked as over-annotation rather than removed because the ISS is a curator judgement about the mouse orthologue. Supporting Evidence: PMID:41639452 PI(4,5)P2 is enriched in the plasma membrane, but also present in the Golgi and endosomes at much lower levels35,37. PI(3,5)P2 is mostly localized to late endosomes and lysosomes35. Upon cGAMP binding, STING traffics to Golgi and Golgi-derived endosomes, but not plasma membrane.
GO:0051607 defense response to virus	NAS PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in...	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:1902554 serine/threonine protein kinase complex	NAS PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in...	MODIFY	Summary: The assembly meant here is the STING1-TBK1 signalosome, not a kinase complex of which STING1 is a subunit. Reason: STING1 recruits and scaffolds TBK1; it is not a constituent subunit of a serine/threonine kinase complex, and the row is NAS from a virology paper. GO:1990231 STING complex is the accurate term and is already annotated. Proposed replacements: STING complex
GO:0002218 activation of innate immune response	IDA PMID:23910378 Structure-function analysis of STING activation by c[G(2',5'...	ACCEPT	Summary: Ligand-bound STING1 activates the innate immune response rather than merely participating in it. Reason: Correct and consistent with the experimental and phylogenetic evidence; kept as-is.
GO:0006914 autophagy	NAS PMID:40861013 Beyond interferons: Non-canonical roles of MITA/STING.	MODIFY	Summary: The autophagy role of STING1 is specifically positive regulation of macroautophagy, which the gene already carries with experimental support. Reason: Correct but the most general possible term, and asserted only as NAS from a review. The child term GO:0016239 states the same thing with IDA and IBA backing. Proposed replacements: positive regulation of macroautophagy Supporting Evidence: PMID:40861013 These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders.
GO:0045087 innate immune response	IDA PMID:23910378 Structure-function analysis of STING activation by c[G(2',5'...	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0045820 negative regulation of glycolysis	NAS PMID:40861013 Beyond interferons: Non-canonical roles of MITA/STING.	MARK AS OVER ANNOTATED	Summary: Asserted only as NAS from a 2025 review of non-canonical MITA/STING roles. Reason: A downstream metabolic consequence of chronic STING1 activation rather than a function of the protein, and supported only by review prose. Not wrong enough to remove, but it should not be read as a curated process role. Supporting Evidence: PMID:40861013 These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders.
GO:0051607 defense response to virus	IDA PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0055088 lipid homeostasis	NAS PMID:40861013 Beyond interferons: Non-canonical roles of MITA/STING.	MARK AS OVER ANNOTATED	Summary: Asserted only as NAS from the same 2025 review. Reason: Same reasoning as the glycolysis row: an indirect, pleiotropic consequence attributed from review text. Over-annotation for a signalling adaptor. Supporting Evidence: PMID:40861013 These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders.
GO:0060340 positive regulation of type I interferon-mediated signaling pathway	IDA PMID:23910378 Structure-function analysis of STING activation by c[G(2',5'...	MODIFY	Summary: STING1 drives interferon production; it does not act within the interferon receptor signalling pathway. Reason: Category confusion between production and response. The experiments underlying these rows measure induction of interferon and interferon-stimulated genes downstream of STING1 activation, which is GO:0032481, a term the gene already carries from ten other references. Proposed replacements: positive regulation of type I interferon production
GO:0090398 cellular senescence	NAS PMID:40861013 Beyond interferons: Non-canonical roles of MITA/STING.	KEEP AS NON CORE	Summary: Chronic cGAS-STING activation is a well-established driver of the senescence-associated secretory phenotype. Reason: Unlike the other review-derived NAS rows, this one is independently well grounded in the wider literature. Kept, but as a non-core, context-dependent role rather than a defining function. Supporting Evidence: PMID:40861013 These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders.
GO:1990231 STING complex	IPI PMID:30405246 Design of amidobenzimidazole STING receptor agonists with sy...	ACCEPT	Summary: STING1 is the defining component of the STING complex. Reason: Correct and specific; supported by IPI and consistent with the homodimer/oligomer structural literature.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0140896 cGAS/STING signaling pathway	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0003713 transcription coactivator activity	IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	MODIFY	Summary: STING1 is a four-pass ER membrane protein that never enters the nucleus; it cannot be a transcription coactivator. Reason: The underlying IDA is real - MITA overexpression activates IFN-beta reporters and MITA binds IRF3 - and an experimental annotation is not deleted on the strength of an abstract. But the GO term is wrong in kind: a transcription coactivator acts on a DNA-bound transcription factor at the promoter, whereas STING1 acts at the ER/Golgi membrane as a scaffold that delivers IRF3 to TBK1. MODIFY to signaling adaptor activity, which GOA already carries for this gene from six other papers, preserves the curator's observation in the right term. This was the most surprising MF row in the set and it does not survive scrutiny as written. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	KEEP AS NON CORE	Summary: STING1 binds IRF3, which is an RNA polymerase II DNA-binding transcription factor, so the term is literally correct. Reason: Unlike the coactivator row from the same paper, this one is accurate: IRF3 is exactly the kind of factor the term describes. Kept as non-core because the informative statement about this interaction is the adaptor activity (GO:0035591), of which it is the mechanistic detail. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0045087 innate immune response	IMP PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0120283 protein serine/threonine kinase binding	IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	ACCEPT	Summary: STING1 recruits the serine/threonine kinase TBK1 through its C-terminal PXPLRXD motif. Reason: Correct and specific. This interaction is the mechanistic core of the adaptor activity, so it is retained rather than being folded into the adaptor term. Supporting Evidence: PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0005515 protein binding	IPI PMID:35013224 Gain-of-function genetic screening identifies the antiviral ...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:32690950 STEEP mediates STING ER exit and activation of signaling.	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0005829 cytosol	TAS Reactome:R-HSA-3244626	MARK AS OVER ANNOTATED	Summary: STING1 is an integral membrane protein; only its C-terminal ligand-binding and signalling domain faces the cytosol. Reason: The rows are an HPA-derived IDA and a Reactome TAS. Cytosol as a location misrepresents the topology of a four-transmembrane protein, though the cytosol-facing domain explains why the signal arises. Supporting Evidence: PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0002221 pattern recognition receptor signaling pathway	IDA PMID:23910378 Structure-function analysis of STING activation by c[G(2',5'...	MODIFY	Summary: STING1 acts in a cytosolic, not membrane-bound, pattern-recognition receptor pathway. Reason: Correct but under-specific. The gene already carries the child term GO:0002753 cytoplasmic pattern recognition receptor signaling pathway from the same and other papers. Proposed replacements: cytoplasmic pattern recognition receptor signaling pathway
GO:0005515 protein binding	IPI PMID:27302953 Structural basis for concerted recruitment and activation of...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005789 endoplasmic reticulum membrane	TAS PMID:33833439 The cGAS-STING pathway as a therapeutic target in inflammato...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0061507 2',3'-cyclic GMP-AMP binding	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0140896 cGAS/STING signaling pathway	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0005789 endoplasmic reticulum membrane	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0032481 positive regulation of type I interferon production	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0035591 signaling adaptor activity	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:37832545 TAK1 is an essential kinase for STING trafficking.	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0000045 autophagosome assembly	IDA PMID:37535724 Human STING is a proton channel.	ACCEPT	Summary: STING1-containing ERGIC membrane serves as the source for LC3 lipidation and autophagosome biogenesis. Reason: Supported by three independent IDA rows plus an IBA, and mechanistically explained: the process is independent of TBK1 and of interferon induction, so it is a real second function rather than a downstream effect of interferon. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway	IDA PMID:35388221 Activation of STING by targeting a pocket in the transmembra...	ACCEPT	Summary: STING1 transduces signals from cytosolic detection of DNA and cyclic dinucleotides. Reason: Correct and specific enough; the still more specific GO:0140896 is also annotated and both are appropriate.
GO:0015252 proton channel activity	IDA PMID:37535724 Human STING is a proton channel.	ACCEPT	Summary: STING1 is a proton channel: its transmembrane domain conducts protons and deacidifies the Golgi, driving an output branch that is separable from interferon induction. Reason: Scrutinised because a proton channel is a non-obvious assignment for an ER adaptor, and it holds. The founding study reconstituted purified STING into liposomes and measured transmembrane proton transport, with the agonist C53 (which binds the channel interface) blocking flux - so the conductance is a property of the protein, not an indirect cellular readout. It has since been used and required by at least three further independent laboratories (Tan lab, PMID:39423796; Miner lab, PMID:39947179; Yan lab, PMID:40185098) and the channel has become a small-molecule binding site. No refutation was found on PubMed search. Treated as a second core molecular function, distinct from the adaptor activity. Note the contrast with TMEM175, where the proton-channel claim genuinely is contested; here it is not. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes. PMID:39423796 STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel. PMID:39947179 Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus. PMID:40185098 This process requires STING's proton channel function, the V-ATPase-ATG5-ATG8 cascade, and is independent of immune signaling. PMID:42336656 The allosteric binding site lies within a hydrophobic transmembrane proton channel formed by intertwined helices of two STING monomers.
GO:0016239 positive regulation of macroautophagy	IDA PMID:37535724 Human STING is a proton channel.	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0032481 positive regulation of type I interferon production	IDA PMID:35388221 Activation of STING by targeting a pocket in the transmembra...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0051259 protein complex oligomerization	IDA PMID:35388221 Activation of STING by targeting a pocket in the transmembra...	KEEP AS NON CORE	Summary: These rows record STING1's own cGAMP-induced oligomerisation. Reason: Accurate but it describes the protein's activation mechanism rather than a biological process it carries out on other entities; the informative statements are the homodimerisation MF and the lipid/cGAMP binding that drive it. The two rows carry different qualifiers (involved_in and acts_upstream_of) for the same self-assembly event, which is itself a sign the term is a poor fit here. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:35388221 Activation of STING by targeting a pocket in the transmembra...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:35388221 Activation of STING by targeting a pocket in the transmembra...	ACCEPT	Summary: The cGAS/STING signalling pathway is the process STING1 exists to run. Reason: Core biological process, supported by fifteen rows from many independent groups spanning 2015-2026. The most specific and most informative BP term on the gene. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0005515 protein binding	IPI PMID:30104205 Inhibition of AIM2 inflammasome activation by a novel transc...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0035591 signaling adaptor activity	IDA PMID:23747010 Cyclic GMP-AMP containing mixed phosphodiester linkages is a...	ACCEPT	Summary: STING1 is the signalling adaptor that couples cyclic-dinucleotide sensing to TBK1 and IRF3; this is its defining molecular activity. Reason: Core molecular function. Phosphorylated STING presents a docking surface that recruits IRF3 for TBK1-dependent phosphorylation, and the same activity underlies NF-kB output. Supported by many independent laboratories and by the structural literature, not by a single group. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. PMID:18818105 MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex.
GO:0140374 antiviral innate immune response	IDA PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	ACCEPT	Summary: The antiviral arm of the innate response is the best-characterised output of STING1 signalling. Reason: Correct and more informative than the generic defense-response term; three independent IDA rows.
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway	IDA PMID:23910378 Structure-function analysis of STING activation by c[G(2',5'...	ACCEPT	Summary: STING1 transduces signals from cytosolic detection of DNA and cyclic dinucleotides. Reason: Correct and specific enough; the still more specific GO:0140896 is also annotated and both are appropriate.
GO:0032481 positive regulation of type I interferon production	IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0000139 Golgi membrane	IDA PMID:29973723 Targeting STING with covalent small-molecule inhibitors.	ACCEPT	Summary: STING1 transits the Golgi, where palmitoylation, clustering and proton efflux occur. Reason: Correct and well supported by independent experimental rows; the Golgi is where the proton channel activity was first measured. Supporting Evidence: PMID:37535724 On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.
GO:0032481 positive regulation of type I interferon production	IDA PMID:29973723 Targeting STING with covalent small-molecule inhibitors.	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1964496	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2396009	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-3134800	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-3134804	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-3244618	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-3244626	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-3244643	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9711016	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9730501	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9730528	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005515 protein binding	IPI PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:29429998 ZDHHC11 modulates innate immune response to DNA virus by med...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:25299331 The ER-associated protein ZDHHC1 is a positive regulator of ...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:30119996 The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiv...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0000045 autophagosome assembly	IDA PMID:30568238 STING directly activates autophagy to tune the innate immune...	ACCEPT	Summary: STING1-containing ERGIC membrane serves as the source for LC3 lipidation and autophagosome biogenesis. Reason: Supported by three independent IDA rows plus an IBA, and mechanistically explained: the process is independent of TBK1 and of interferon induction, so it is a real second function rather than a downstream effect of interferon. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0000045 autophagosome assembly	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: STING1-containing ERGIC membrane serves as the source for LC3 lipidation and autophagosome biogenesis. Reason: Supported by three independent IDA rows plus an IBA, and mechanistically explained: the process is independent of TBK1 and of interferon induction, so it is a real second function rather than a downstream effect of interferon. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0005515 protein binding	IPI PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005768 endosome	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	MODIFY	Summary: STING1 is an integral membrane protein, so the membrane of the endosome is the correct component. Reason: Correct but under-specific for a polytopic membrane protein; GO:0010008 endosome membrane is already annotated on this gene and states the location precisely. Proposed replacements: endosome membrane
GO:0005776 autophagosome	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	ACCEPT	Summary: STING1 is found on autophagosomes formed from STING-containing ERGIC membrane. Reason: Consistent with the autophagy-related process annotations and with the ERGIC-as-membrane-source mechanism. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	IDA PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0005789 endoplasmic reticulum membrane	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0016239 positive regulation of macroautophagy	IDA PMID:30568238 STING directly activates autophagy to tune the innate immune...	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0016239 positive regulation of macroautophagy	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: Activated STING1 positively regulates macroautophagy, through both its trafficking and its proton channel. Reason: Well supported experimentally and phylogenetically. The proton-channel work supplies the molecular mechanism (H+ efflux promoting LC3B/GABARAP lipidation), which makes this annotation mechanistically coherent rather than merely correlative. Supporting Evidence: PMID:30842662 Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. PMID:37535724 STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity is critical for these two processes.
GO:0032481 positive regulation of type I interferon production	IDA PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosoli...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0032481 positive regulation of type I interferon production	IDA PMID:23747010 Cyclic GMP-AMP containing mixed phosphodiester linkages is a...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0032481 positive regulation of type I interferon production	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0032481 positive regulation of type I interferon production	IDA PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: On activation STING1 buds from the ER in COPII vesicles into the ERGIC, where TBK1 is recruited and where LC3 lipidation is nucleated. Reason: Core location for the activated protein, and arguably the single most informative CC term on the gene: ERGIC residence is what couples trafficking to signalling competence. Supporting Evidence: PMID:30842662 Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. PMID:41887218 Stimulator of interferon genes (STING) activation requires coat protein complex II (COPII)-mediated endoplasmic reticulum (ER) exit, but the mechanism remains elusive.
GO:0035438 cyclic-di-GMP binding	IDA PMID:29694889 Pro-inflammation Associated with a Gain-of-Function Mutation...	ACCEPT	Summary: STING1 binds bacterial cyclic di-GMP directly, acting as a sensor for bacterial cyclic dinucleotides as well as for host cGAMP. Reason: Core molecular function. Direct radioligand binding with competition by unlabelled cyclic dinucleotides but not by other nucleotides, plus mutations that selectively impair the cyclic-dinucleotide response. This is the activity that grounds the antibacterial innate immune annotations. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0051259 protein complex oligomerization	IDA PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	KEEP AS NON CORE	Summary: These rows record STING1's own cGAMP-induced oligomerisation. Reason: Accurate but it describes the protein's activation mechanism rather than a biological process it carries out on other entities; the informative statements are the homodimerisation MF and the lipid/cGAMP binding that drive it. The two rows carry different qualifiers (involved_in and acts_upstream_of) for the same self-assembly event, which is itself a sign the term is a poor fit here. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:23747010 Cyclic GMP-AMP containing mixed phosphodiester linkages is a...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:30842659 Cryo-EM structures of STING reveal its mechanism of activati...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:30842662 Autophagy induction via STING trafficking is a primordial fu...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0061709 reticulophagy	ISS GO_REF:0000024	ACCEPT	Summary: Cyclic-di-GMP-triggered STING1 signalling has been linked to selective autophagy of the ER. Reason: The weakest member of the autophagy cluster: UniProt supports it only "By similarity", and the human evidence is IBA/IEA/ISS with no direct experimental row. Kept as-is rather than downgraded because doing so would require asserting a propagation failure in the PANTHER family (PTN005046674) that I did not inspect, and because ER-derived membrane is genuinely the source of STING-induced autophagosomes. Flagged here as the annotation on this gene I would most like to see experimentally confirmed or retired.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:25254379 RNF26 temporally regulates virus-triggered type I interferon...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0032728 positive regulation of interferon-beta production	IDA PMID:25254379 RNF26 temporally regulates virus-triggered type I interferon...	ACCEPT	Summary: IFN-beta is the principal type I interferon induced downstream of STING1. Reason: Correct and more specific than the parent type I interferon term; retained alongside it. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0045087 innate immune response	IDA PMID:25254379 RNF26 temporally regulates virus-triggered type I interferon...	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0051607 defense response to virus	IDA PMID:25254379 RNF26 temporally regulates virus-triggered type I interferon...	ACCEPT	Summary: STING1 restricts DNA viruses and, via NF-kB, also contributes to control of some RNA viruses. Reason: Well supported experimentally and phylogenetically; a genuine biological role of the pathway. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0005515 protein binding	IPI PMID:24560620 NLRC3, a member of the NLR family of proteins, is a negative...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798743	MARK AS OVER ANNOTATED	Summary: Plasma membrane localisation has no human experimental support and is contradicted by the trafficking literature. Reason: The three rows are IEA from UniProt subcellular-location mapping, ISS, and a generic Reactome exocytosis reaction; UniProt itself qualifies "Cell membrane" as ECO:0000250 by similarity to mouse Q3TBT3. The 2026 lipid work states positively that activated STING1 traffics to the Golgi and Golgi-derived endosomes but not to the plasma membrane. Marked as over-annotation rather than removed because the ISS is a curator judgement about the mouse orthologue. Supporting Evidence: PMID:41639452 PI(4,5)P2 is enriched in the plasma membrane, but also present in the Golgi and endosomes at much lower levels35,37. PI(3,5)P2 is mostly localized to late endosomes and lysosomes35. Upon cGAMP binding, STING traffics to Golgi and Golgi-derived endosomes, but not plasma membrane.
GO:0030667 secretory granule membrane	TAS Reactome:R-HSA-6798743	MARK AS OVER ANNOTATED	Summary: A single TAS row from a generic Reactome neutrophil-degranulation reaction. Reason: Secretory granule membrane is not a described STING1 location in any primary study; it is an artefact of a broad proteomic Reactome pathway that also generates the plasma membrane TAS row.
GO:0032481 positive regulation of type I interferon production	IDA PMID:26669264 Rat and human STINGs profile similarly towards anticancer/an...	ACCEPT	Summary: Activated STING1 drives transcriptional induction of type I interferons. Reason: Core biological process and the canonical output of the pathway; ten independent experimental rows plus an IBA. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0061507 2',3'-cyclic GMP-AMP binding	IDA PMID:26669264 Rat and human STINGs profile similarly towards anticancer/an...	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0005515 protein binding	IPI PMID:22908223 Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-in...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-1834939	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-2396002	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-2396007	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-2396009	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-3244643	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-3249371	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-3249378	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-3249390	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-3249392	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0030659 cytoplasmic vesicle membrane	TAS Reactome:R-HSA-8948709	MODIFY	Summary: These ten Reactome-derived rows describe the post-ER vesicular compartment that is now identified specifically as the ERGIC. Reason: Correct but uninformative. All ten are TAS from Reactome reactions modelling activated STING1 in post-ER vesicles; the compartment has since been resolved as the ER-Golgi intermediate compartment, which the gene already carries with eight experimental rows. Proposed replacements: endoplasmic reticulum-Golgi intermediate compartment membrane
GO:0061507 2',3'-cyclic GMP-AMP binding	ISS GO_REF:0000024	ACCEPT	Summary: STING1 binds 2'3'-cGAMP, the cGAS second messenger, with high affinity; this is the receptor event that starts the pathway. Reason: Core molecular function, established by direct binding and co-crystal structure and independently reproduced. The IBA row is consistent with the experimental rows on the gene itself. Supporting Evidence: PMID:23747010 This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages.
GO:0035438 cyclic-di-GMP binding	IDA PMID:22705373 Cyclic di-GMP sensing via the innate immune signaling protei...	ACCEPT	Summary: STING1 binds bacterial cyclic di-GMP directly, acting as a sensor for bacterial cyclic dinucleotides as well as for host cGAMP. Reason: Core molecular function. Direct radioligand binding with competition by unlabelled cyclic dinucleotides but not by other nucleotides, plus mutations that selectively impair the cyclic-dinucleotide response. This is the activity that grounds the antibacterial innate immune annotations. Supporting Evidence: PMID:21947006 We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING.
GO:0042803 protein homodimerization activity	IDA PMID:22705373 Cyclic di-GMP sensing via the innate immune signaling protei...	ACCEPT	Summary: STING1 is an obligate homodimer, and cGAMP-induced side-by-side packing of dimers into tetramers and higher-order oligomers is the activation mechanism. Reason: Well supported by multiple independent crystal and cryo-EM structures as well as biochemistry. Retained as a genuine molecular function because oligomerisation state, not just ligand occupancy, is what licenses ER exit and TBK1 activation. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0019901 protein kinase binding	IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	MODIFY	Summary: The kinase STING1 binds is TBK1, a serine/threonine kinase; a more specific term is available and already annotated here. Reason: Correct but under-specific. GO:0120283 protein serine/threonine kinase binding is the precise term for the TBK1 interaction and is already on the gene from the same source paper. Proposed replacements: protein serine/threonine kinase binding
GO:0002230 positive regulation of defense response to virus by host	IMP PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	ACCEPT	Summary: Loss-of-function experiments show STING1 is required for a normal antiviral defence response in the host. Reason: IMP evidence; consistent with the wider literature and with the defense-response-to-virus annotations.
GO:0005515 protein binding	IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	REMOVE	Summary: Twenty-five bare protein-binding IPI rows from large interaction screens and single-partner papers. Reason: 'Per project curation guidance, bare protein binding carries no functional information. The informative content of these rows is captured by the specific terms this gene already has: signaling adaptor activity, protein serine/threonine kinase binding, ubiquitin protein ligase binding, homodimerisation and STING complex membership.'. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005741 mitochondrial outer membrane	IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	MARK AS OVER ANNOTATED	Summary: Mitochondrial outer membrane localisation comes entirely from 2008-2009 reports and is not how STING1 is understood today. Reason: Six rows, four EXP plus one IDA, all from the first two years of work on the protein, and UniProt still lists the location with those same four references. Every subsequent structural and trafficking study places STING1 in the ER and its post-ER itinerary, and the same UniProt entry's FUNCTION block describes only that route. The early mitochondrial signal is plausibly mitochondria-associated ER membrane (MAM) rather than the outer mitochondrial membrane proper. Not removed, because these are experimental annotations whose full texts I have not read and which I have no standing to overturn, but marked as over-annotation so that it is not read as a current localisation. Supporting Evidence: PMID:18818105 MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	MODIFY	Summary: The transcriptional upregulation STING1 causes is specifically the induction of type I interferon and inflammatory cytokine genes. Reason: Correct but too general and indirect for a membrane-anchored signalling adaptor. The informative term is GO:0032481, already annotated from the same era of work. Proposed replacements: positive regulation of type I interferon production
GO:0071360 cellular response to exogenous dsRNA	IMP PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR...	KEEP AS NON CORE	Summary: STING1 knockdown blunts responses to transfected dsRNA in the original MITA study. Reason: Plausible and not challenged, but peripheral: STING1 is a DNA/cyclic-dinucleotide sensing adaptor, and its contribution to dsRNA responses is indirect, through crosstalk with the RIG-I/MAVS axis. Retained as non-core rather than removed, since it rests on an experimental (IMP) observation whose full text I have not read.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	ACCEPT	Summary: The endoplasmic reticulum membrane is where resting STING1 resides and where it is activated by cGAMP before ER exit. Reason: Core location, with twenty-seven rows spanning experimental, phylogenetic, electronic and Reactome sources across two decades. STING1 is a polytopic ER membrane protein with four transmembrane helices. Supporting Evidence: PMID:30842659 STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain PMID:41639452 STING is an endoplasmic reticulum (ER) membrane protein comprising four transmembrane (TM) helices forming the TM domain (TMD), a cytoplasmic ligand-binding domain (LBD) responsible for cGAMP binding, and a C-terminal tail containing both the phosphorylation site (Ser366) and the PXPLRXD
GO:0019901 protein kinase binding	IPI PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	MODIFY	Summary: The kinase STING1 binds is TBK1, a serine/threonine kinase; a more specific term is available and already annotated here. Reason: Correct but under-specific. GO:0120283 protein serine/threonine kinase binding is the precise term for the TBK1 interaction and is already on the gene from the same source paper. Proposed replacements: protein serine/threonine kinase binding
GO:0032728 positive regulation of interferon-beta production	IMP PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	ACCEPT	Summary: IFN-beta is the principal type I interferon induced downstream of STING1. Reason: Correct and more specific than the parent type I interferon term; retained alongside it. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0032728 positive regulation of interferon-beta production	IDA PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	ACCEPT	Summary: IFN-beta is the principal type I interferon induced downstream of STING1. Reason: Correct and more specific than the parent type I interferon term; retained alongside it. Supporting Evidence: PMID:25636800 Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.
GO:0042803 protein homodimerization activity	IDA PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	ACCEPT	Summary: STING1 is an obligate homodimer, and cGAMP-induced side-by-side packing of dimers into tetramers and higher-order oligomers is the activation mechanism. Reason: Well supported by multiple independent crystal and cryo-EM structures as well as biochemistry. Retained as a genuine molecular function because oligomerisation state, not just ligand occupancy, is what licenses ER exit and TBK1 activation. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0042803 protein homodimerization activity	IDA PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	ACCEPT	Summary: STING1 is an obligate homodimer, and cGAMP-induced side-by-side packing of dimers into tetramers and higher-order oligomers is the activation mechanism. Reason: Well supported by multiple independent crystal and cryo-EM structures as well as biochemistry. Retained as a genuine molecular function because oligomerisation state, not just ligand occupancy, is what licenses ER exit and TBK1 activation. Supporting Evidence: PMID:30842659 This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing.
GO:0045087 innate immune response	IMP PMID:19433799 ERIS, an endoplasmic reticulum IFN stimulator, activates inn...	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0045087 innate immune response	IDA PMID:21074459 The ubiquitin ligase TRIM56 regulates innate immune response...	ACCEPT	Summary: STING1 is a central node of the innate immune response to cytosolic DNA and bacterial cyclic dinucleotides. Reason: Correct though general. Retained as-is: the IBA row rests on a phylogenetic judgement across the STING family that I did not re-examine, and the more specific terms the gene carries (cGAS/STING signalling pathway, antiviral and antibacterial innate immune response) already supply the detail.
GO:0048471 perinuclear region of cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: Activated STING1 accumulates in perinuclear vesicle clusters, and this clustering is required for TBK1 activation. Reason: Correct and functionally meaningful rather than incidental: perinuclear clustering is the step at which high-order oligomers support TBK1 trans-autophosphorylation. Supporting Evidence: PMID:41639454 STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding	IDA PMID:41639452 Regulation of STING activation by phosphoinositide and chole...	NEW	Summary: STING1 binds PtdIns(4,5)P2 in the same transmembrane groove that binds PtdIns(3,5)P2, with comparable potency in promoting high-order oligomerisation. Reason: GOA already captures the PtdIns(3,5)P2 half of the 2026 lipid work (GO:0080025) but not this one, although it rests on the same evidence: a dedicated cryo-EM structure of the STING/PI(4,5)P2 complex, native-PAGE oligomerisation assays, and lipid-strip binding abolished by the R71H/K20E mutation. Proposed with an explicit caveat rather than as a settled fact: PtdIns(4,5)P2 is plasma-membrane-enriched and activated STING1 does not traffic to the plasma membrane, so although the binding capability is well demonstrated its physiological occupancy is not established - the authors themselves note this and argue PtdIns(3,5)P2 is the more likely in-cell ligand. It is also, like GO:0080025, single-programme evidence from companion papers rather than independently replicated. Annotated as the specific term matching the lipid actually assayed; a curator preferring a single annotation over two could instead use the parent GO:1902936 phosphatidylinositol bisphosphate binding. PtdIns4P was deliberately not annotated, since the same paper argues its effect is probably indirect. Supporting Evidence: PMID:41639452 Our lipid binding, native PAGE and cryo-EM studies together indicate that both PI(3,5)P2 and PI(4,5)P2 are able to strongly bind STING and effectively induce high-order STING oligomerization. PMID:41639452 Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 and PtdIns(4,5)P2, and by PtdIns4P to a lesser extent. PMID:41639452 PI(4,5)P2 is enriched in the plasma membrane, but also present in the Golgi and endosomes at much lower levels35,37. PI(3,5)P2 is mostly localized to late endosomes and lysosomes35. Upon cGAMP binding, STING traffics to Golgi and Golgi-derived endosomes, but not plasma membrane. PMID:41639452 It is possible that this effect of PI(4)P is indirect, as changes in the concentration of PI(4)P could affect other PIP species such as PI(4,5)P2 and PI(3,5)P2.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

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