Interferon regulatory factor 3 (IRF3) is a constitutively expressed, signal-activated transcription factor of the interferon regulatory factor (IRF) family and the principal transcriptional activator of the type I interferon (IFN-alpha/beta) response to viral infection. It has an N-terminal winged-helix DNA-binding domain bearing the IRF tryptophan pentad repeat, which recognizes GAAA-containing interferon-stimulated response elements (ISRE) and IRF/PRD sites, and a C-terminal IRF-association/regulatory domain that maintains the protein as an autoinhibited cytoplasmic monomer in resting cells. Cytosolic nucleic-acid sensing (RIG-I/MDA5 signaling through MAVS for RNA, cGAS signaling through STING for DNA) and TLR3/TLR4 signaling through TRIF converge on the kinases TBK1 and IKBKE, which phosphorylate a conserved pLxIS motif on the adaptors; phospho-adaptors recruit IRF3 and license its phosphorylation by TBK1 at Ser-385/386/396. Phosphorylation relieves autoinhibition, driving IRF3 homodimerization, nuclear accumulation, sequence-specific DNA binding, and recruitment of the coactivators CBP/p300 to form the DRAF1/enhanceosome complex that activates transcription of IFN-beta, IFN-alpha and interferon-stimulated genes. IRF3 shuttles between cytoplasm and nucleus and is heavily regulated by post-translational modification (phosphorylation, Ser-386 pyrophosphorylation by UAP1, ISGylation, ubiquitination, acetylation, deamidation and caspase cleavage). Beyond transcription, activated IRF3 can be recruited to mitochondria by a TOMM70/HSP90 complex and drive a transcription-independent, BAX-dependent apoptotic program. Loss-of-function of IRF3 predisposes to herpes simplex encephalitis, and IRF3 is a major target of viral immune-evasion proteins.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Negative regulation of transcription by RNA polymerase II, inferred from the transferred repressor activity annotation, which rests on a mouse splice isoform (PMID:18851954). Reason: This process term is inferred automatically from the DNA-binding transcription repressor activity annotation, which is transferred from mouse Irf3 and rests on the splice isoform mIRF-3a repressing the Ifn-beta promoter (PMID:18851954). That activity is marked in this review as an over-annotation for the canonical activator protein rather than removed, and this row follows it: it over-extends an isoform-specific finding but is not without experimental basis. |
| GO:0000785 chromatin | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: Activated IRF3 associates with chromatin at target gene promoters. Reason: Consistent with sequence-specific promoter binding and coactivator recruitment. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Activated IRF3 associates with chromatin at target gene promoters. Reason: Consistent with sequence-specific promoter binding and coactivator recruitment. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000002 | ACCEPT | Summary: IRF3 binds cis-regulatory (ISRE/IRF) DNA elements; the InterPro-based electronic annotation is correct though less specific than the experimental cis-regulatory DNA-binding terms. Reason: Consistent with the IRF DNA-binding domain and experimental ISRE binding. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IRF3 is a sequence-specific transcription factor that binds ISRE/PRD cis-regulatory elements in RNA polymerase II promoters (e.g. the IFN-beta enhancer PRDIII-I element). Reason: Core molecular function, established biochemically and structurally and supported at the correct level of specificity by the IBA. IRF3's presence in its own IBA WITH/FROM reflects experimental grounding on the target. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 is a sequence-specific transcription factor that binds ISRE/PRD cis-regulatory elements in RNA polymerase II promoters (e.g. the IFN-beta enhancer PRDIII-I element). Reason: Core molecular function, established biochemically and structurally and supported at the correct level of specificity by the IBA. IRF3's presence in its own IBA WITH/FROM reflects experimental grounding on the target. Supporting Evidence: PMID:8524823 IFN-stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 is a sequence-specific transcription factor that binds ISRE/PRD cis-regulatory elements in RNA polymerase II promoters (e.g. the IFN-beta enhancer PRDIII-I element). Reason: Core molecular function, established biochemically and structurally and supported at the correct level of specificity by the IBA. IRF3's presence in its own IBA WITH/FROM reflects experimental grounding on the target. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IMP PMID:17560375 Structure of IRF-3 bound to the PRDIII-I regulatory element ... | ACCEPT | Summary: IRF3 is a sequence-specific transcription factor that binds ISRE/PRD cis-regulatory elements in RNA polymerase II promoters (e.g. the IFN-beta enhancer PRDIII-I element). Reason: Core molecular function, established biochemically and structurally and supported at the correct level of specificity by the IBA. IRF3's presence in its own IBA WITH/FROM reflects experimental grounding on the target. Supporting Evidence: PMID:17560375 IRF-3 molecules bind in tandem to, variably spaced, consensus and nonconsensus |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription factor. Reason: Core molecular function; the IBA sits at the correct level for the IRF family and includes IRF3's own experimental annotation among its sources. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription factor. Reason: Core molecular function; the IBA sits at the correct level for the IRF family and includes IRF3's own experimental annotation among its sources. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription factor. Reason: Core molecular function; the IBA sits at the correct level for the IRF family and includes IRF3's own experimental annotation among its sources. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription factor. Reason: Core molecular function; the IBA sits at the correct level for the IRF family and includes IRF3's own experimental annotation among its sources. |
| GO:0001216 DNA-binding transcription activator activity | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 acts as a DNA-binding transcriptional activator of interferon-stimulated (ISRE-containing) genes. Reason: Core function; the founding paper shows IRF3 activates the ISG15 (ISRE) promoter. Supporting Evidence: PMID:8524823 Overexpression of IRF-3 stimulates expression of the IFN-stimulated gene 15 |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: DNA-binding transcription repressor activity (IEA), transferred from mouse Irf3, where it was shown for the splice isoform mIRF-3a, which represses the Ifn-beta promoter (PMID:18851954). Reason: The row is transferred from mouse Irf3, where repressor activity was shown by direct assay for mIRF-3a, an alternatively spliced isoform that binds ISRE sequences in the Ifn-beta promoter and represses promoter activity (PMID:18851954). The transfer therefore has an experimental source, but the activity belongs to a specific splice isoform that opposes the canonical protein, whereas full-length IRF3 is characterized as a transcriptional activator of type I interferon and interferon-stimulated genes. Assigning repressor activity to human IRF3 as a whole over-extends an isoform-specific finding; it is marked as an over-annotation rather than removed as unsupported. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IMP PMID:17560375 Structure of IRF-3 bound to the PRDIII-I regulatory element ... | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription activator, the terminal effector of the type I IFN induction pathways. Reason: Core molecular function, supported by IMP (interferon-beta enhancer activation) and by the broader literature. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: IRF3 is an RNA polymerase II-specific DNA-binding transcription activator, the terminal effector of the type I IFN induction pathways. Reason: Core molecular function, supported by IMP (interferon-beta enhancer activation) and by the broader literature. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 positively regulates production of cytokines (chiefly type I IFNs). Reason: Correct although broad; a general parent of the more specific type I IFN production terms. |
| GO:0002376 immune system process | IBA GO_REF:0000033 | ACCEPT | Summary: IRF3 participates in the immune system process (innate antiviral immunity). Reason: High-level grouping term appropriate for the IRF family IBA; correct but non-specific. |
| GO:0002753 cytoplasmic pattern recognition receptor signaling pathway | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 is the terminal transcription factor of cytoplasmic pattern-recognition-receptor signaling (RIG-I/MDA5-MAVS and cGAS-STING). Reason: Core biological process; IRF3 executes the transcriptional output step of these cytosolic sensing pathways. |
| GO:0003677 DNA binding | NAS PMID:12062447 Involvement of TIRAP/MAL in signaling for the activation of ... | MODIFY | Summary: Generic 'DNA binding'; IRF3 binds DNA in a sequence-specific manner (ISRE/IRF elements). Reason: The more informative and evidence-supported term is sequence-specific double-stranded DNA binding; the generic parent under-describes the characterized function. Proposed replacements: sequence-specific double-stranded DNA binding |
| GO:0003700 DNA-binding transcription factor activity | IC PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 is a DNA-binding transcription factor; this is the general parent of the RNA Pol II-specific term also annotated. Reason: Correct though less specific than GO:0000981; retained as an accurate higher-level assertion. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:36603579 Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to f... | ACCEPT | Summary: IRF3 is a DNA-binding transcription factor; this is the general parent of the RNA Pol II-specific term also annotated. Reason: Correct though less specific than GO:0000981; retained as an accurate higher-level assertion. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 is a DNA-binding transcription factor; this is the general parent of the RNA Pol II-specific term also annotated. Reason: Correct though less specific than GO:0000981; retained as an accurate higher-level assertion. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: IRF3 is a DNA-binding transcription factor; this is the general parent of the RNA Pol II-specific term also annotated. Reason: Correct though less specific than GO:0000981; retained as an accurate higher-level assertion. |
| GO:0005515 protein binding | IDA PMID:10920266 Analyses of virus-induced homomeric and heteromeric protein ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:15841462 Interaction between the HCV NS3 protein and the host TBK1 pr... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:16154084 Crystal structure of IRF-3 in complex with CBP. | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:16362036 The GRIP1:IRF3 interaction as a target for glucocorticoid re... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:17599067 Involvement of the ubiquitin-like domain of TBK1/IKK-i kinas... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:17761676 Regulation of IRF-3-dependent innate immunity by the papain-... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:17761676 Regulation of IRF-3-dependent innate immunity by the papain-... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:18309294 S-glutathionylation of IRF3 regulates IRF3-CBP interaction a... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:18583960 The DEAD-box helicase DDX3X is a critical component of the T... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:18711448 Negative feedback regulation of cellular antiviral signaling... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:19153231 Ebola virus protein VP35 impairs the function of interferon ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:19153231 Ebola virus protein VP35 impairs the function of interferon ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:20308324 Positive regulation of interferon regulatory factor 3 activa... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:20581830 The transcription factor MafB antagonizes antiviral response... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:20581830 The transcription factor MafB antagonizes antiviral response... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:22908223 Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-in... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:23746807 Structural insights into the functions of TBK1 in innate ant... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:24622840 SARS coronavirus papain-like protease inhibits the type I in... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:24807708 RIOK3 is an adaptor protein required for IRF3-mediated antiv... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:24807708 RIOK3 is an adaptor protein required for IRF3-mediated antiv... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:25803835 Haploinsufficiency of TBK1 causes familial ALS and fronto-te... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:26347139 TRIM-mediated precision autophagy targets cytoplasmic regula... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:27980081 DDX3 directly regulates TRAF3 ubiquitination and acts as a s... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:27980081 DDX3 directly regulates TRAF3 ubiquitination and acts as a s... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:29429998 ZDHHC11 modulates innate immune response to DNA virus by med... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:29802199 C6orf106 is a novel inhibitor of the interferon-regulatory f... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:31413131 LYAR Suppresses Beta Interferon Induction by Targeting Phosp... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32726803 Papain-like protease regulates SARS-CoV-2 viral spread and i... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32878885 IRF1 Promotes the Innate Immune Response to Viral Infection ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32878885 IRF1 Promotes the Innate Immune Response to Viral Infection ... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)... | REMOVE | Summary: Generic protein-binding annotation supported by a specific pairwise interaction; it conveys no information about IRF3's own molecular function. Reason: Per curation policy the uninformative GO:0005515 'protein binding' term is removed; removal does not dispute that the reported interaction occurs. IRF3's informative molecular functions (sequence-specific DNA binding, DNA-binding transcription activator activity, phosphorylation-induced homodimerization) are captured by dedicated terms elsewhere in this review. |
| GO:0005634 nucleus | EXP PMID:31340999 DDX56 inhibits type I interferon by disrupting assembly of I... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | EXP PMID:31413131 LYAR Suppresses Beta Interferon Induction by Targeting Phosp... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | EXP PMID:35922005 Coronaviruses exploit a host cysteine-aspartic protease for ... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | EXP PMID:39761299 USP5 inhibits anti-RNA viral innate immunity by deconjugatin... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IDA PMID:10805757 Regulated nuclear-cytoplasmic localization of interferon reg... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IDA PMID:17079289 Inhibition of retinoic acid-inducible gene I-mediated induct... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IDA PMID:36603579 Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to f... | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Activated IRF3 translocates to and is active in the nucleus, where it drives transcription. Reason: Core localization; extensively documented (EXP/IDA) and captured by the IBA with IRF3 among its sources. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1028815 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1028816 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1028817 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1028819 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1028820 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-177671 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2032396 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3134883 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-936380 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-936462 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9768142 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9833441 | ACCEPT | Summary: IRF3 functions in the nucleoplasm as a transcription factor. Reason: Nuclear subcompartment localization consistent with its transcriptional role; Reactome-traceable. |
| GO:0005737 cytoplasm | EXP PMID:10805757 Regulated nuclear-cytoplasmic localization of interferon reg... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:31340999 DDX56 inhibits type I interferon by disrupting assembly of I... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:31413131 LYAR Suppresses Beta Interferon Induction by Targeting Phosp... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:35922005 Coronaviruses exploit a host cysteine-aspartic protease for ... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:36603579 Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to f... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | EXP PMID:39761299 USP5 inhibits anti-RNA viral innate immunity by deconjugatin... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | IDA PMID:17079289 Inhibition of retinoic acid-inducible gene I-mediated induct... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | IDA PMID:18818105 The adaptor protein MITA links virus-sensing receptors to IR... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | IDA PMID:9566918 Virus-dependent phosphorylation of the IRF-3 transcription f... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005737 cytoplasm | IGI PMID:23729669 Inducible interleukin 32 (IL-32) exerts extensive antiviral ... | ACCEPT | Summary: In resting cells IRF3 is a cytoplasmic autoinhibited monomer, activated and exported/imported through the cytoplasm. Reason: Core localization, extensively documented experimentally. |
| GO:0005739 mitochondrion | EXP PMID:39362857 PBLD promotes IRF3 mediated the type I interferon (IFN-I) re... | KEEP AS NON CORE | Summary: Upon viral infection IRF3 can be recruited to mitochondria (via TOMM70/HSP90) to drive a BAX-dependent apoptotic program. Reason: A genuine but condition-specific, non-core localization tied to IRF3's secondary pro-apoptotic role rather than its central nuclear transcriptional function. ORGANELLES check (2026-10-25): the PBLD study isolates mitochondrial and cytosolic fractions with TOMM20 and beta-actin as markers (no ER marker) and shows IRF3 with Puma in the mitochondrial fraction; the assay resolves only the organelle. Stays at the root (see the IEA row for why GO:0005741 is not added). Supporting Evidence: PMID:39362857 Ξ²-actin and TOMM20 were utilized as markers for the cytosolic and mitochondrial fractions, respectively. |
| GO:0005739 mitochondrion | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | KEEP AS NON CORE | Summary: Upon viral infection IRF3 can be recruited to mitochondria (via TOMM70/HSP90) to drive a BAX-dependent apoptotic program. Reason: A genuine but condition-specific, non-core localization tied to IRF3's secondary pro-apoptotic role rather than its central nuclear transcriptional function. ORGANELLES check (2026-10-25): subcellular fractionation shows ectopic and endogenous IRF3 relocalizing to mitochondria on Sendai virus infection, dependent on Tom70 but not Tom20; the assay resolves the organelle, not a sub-compartment. Stays at the root (see the IEA row). Supporting Evidence: PMID:25609812 The mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Upon viral infection IRF3 can be recruited to mitochondria (via TOMM70/HSP90) to drive a BAX-dependent apoptotic program. Reason: A genuine but condition-specific, non-core localization tied to IRF3's secondary pro-apoptotic role rather than its central nuclear transcriptional function. ORGANELLES check (2026-10-25), examined as a synthesis row. GO_REF:0000044 maps UniProt SL-0173 (Mitochondrion), which UniProt records with ECO:0000269 from PMID:25609812 and PMID:39362857, so the mapping is sound. IRF3 is a soluble cytosolic transcription factor (no transit peptide or TM segment) recruited to the mitochondrial surface by outer-membrane Tom70 via Hsp90, a recruited surface pool like TRAF3 and BRAF. The only sub-compartment line is binding to an outer-membrane receptor, and no cached study shows IRF3 in an outer-membrane fraction or protease-accessibility assay, so GO:0005741 is not added. Supporting Evidence: file:human/IRF3/IRF3-uniprot.txt Mitochondrion {ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:39362857}. PMID:25609812 Tom70 resides on the outer membrane of mitochondria, whereas IRF3 is located in the cytosol of resting cells. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1015702 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1028816 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1028821 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1031716 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169394 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1606327 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166245 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-166271 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168933 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177671 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1834939 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2032396 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2395992 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396002 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396007 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3249392 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948709 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013978 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013979 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918229 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-918232 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709831 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709852 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9729725 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9729730 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9731009 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9731077 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9768142 | ACCEPT | Summary: IRF3 resides in the cytosol in resting cells prior to activation. Reason: Consistent with the cytoplasmic localization of inactive IRF3. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: IRF3 regulates DNA-templated transcription. Reason: Correct general parent term; more specific Pol II regulation terms are also annotated. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IRF3 regulates RNA polymerase II transcription of its target genes. Reason: Appropriate family-level IBA that includes IRF3's own experimental annotation among its sources. |
| GO:0006915 apoptotic process | TAS PMID:20049431 Regulation of immunity and oncogenesis by the IRF transcript... | KEEP AS NON CORE | Summary: IRF3 contributes to a virus-induced apoptotic program. Reason: A real but secondary function; IRF3's core role is transcriptional induction of type I IFN. Kept as non-core. |
| GO:0006974 DNA damage response | TAS PMID:16979567 Type I interferon [corrected] gene induction by the interfer... | MARK AS OVER ANNOTATED | Summary: DNA damage response, cited (TAS) to a type I IFN induction review. Reason: IRF3's DNA-related role is sensing of cytosolic/viral DNA via cGAS-STING (captured by GO:0140896), not the canonical DNA damage response. The cited review concerns IFN gene induction and does not establish a DDR role; flagged as likely over-annotation. |
| GO:0019904 protein domain specific binding | IPI PMID:11583620 A small domain of CBP/p300 binds diverse proteins: solution ... | KEEP AS NON CORE | Summary: Protein-domain-specific binding (to the CBP/p300 KIX domain); an uninformative binding term for IRF3's function. Reason: The cited structural study identified the IRF-3 binding domain (IBiD) of CBP/p300 and showed that IRF3 binds this compact domain (PMID:11583620), so the row records a real, domain-specific interaction with an experimentally defined partner domain. The term says less than the coactivator recruitment it reflects, but it is true as stated, and a true annotation is not removed for being uninformative. Binding to the coactivator domain serves transcriptional activation, which is captured by the core activator terms, so this row is kept as non-core. Supporting Evidence: PMID:11583620 We have identified a compactly folded 46 residue domain in CBP and p300, the IRF-3 binding domain (IBiD), and we have determined its structure by NMR. |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:18636090 Viral targeting of DEAD box protein 3 reveals its role in TB... | ACCEPT | Summary: Positive regulation of type I interferon production is IRF3's central biological function. Reason: Core process, supported by multiple direct experimental studies of IRF3 activation driving IFN induction. |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: Positive regulation of type I interferon production is IRF3's central biological function. Reason: Core process, supported by multiple direct experimental studies of IRF3 activation driving IFN induction. Supporting Evidence: PMID:25636800 phosphorylation and activation by TBK1. |
| GO:0032481 positive regulation of type I interferon production | IDA PMID:36603579 Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to f... | ACCEPT | Summary: Positive regulation of type I interferon production is IRF3's central biological function. Reason: Core process, supported by multiple direct experimental studies of IRF3 activation driving IFN induction. Supporting Evidence: PMID:36603579 pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 |
| GO:0032481 positive regulation of type I interferon production | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of type I interferon production is IRF3's central biological function. Reason: Core process, supported by multiple direct experimental studies of IRF3 activation driving IFN induction. |
| GO:0032727 positive regulation of interferon-alpha production | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 contributes to positive regulation of IFN-alpha production, particularly early/late-phase induction. Reason: Consistent with its role in type I IFN induction; IRF3 is a more potent activator of IFN-beta but also contributes to IFN-alpha genes. |
| GO:0032727 positive regulation of interferon-alpha production | ISS GO_REF:0000024 | ACCEPT | Summary: IRF3 contributes to positive regulation of IFN-alpha production, particularly early/late-phase induction. Reason: Consistent with its role in type I IFN induction; IRF3 is a more potent activator of IFN-beta but also contributes to IFN-alpha genes. |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:31390091 TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiv... | ACCEPT | Summary: IRF3 is the principal positive regulator of IFN-beta production. Reason: Core function; IRF3 is a more potent activator of the IFN-beta gene than IFN-alpha and is essential for IFN-beta enhanceosome assembly. |
| GO:0032728 positive regulation of interferon-beta production | IEA GO_REF:0000120 | ACCEPT | Summary: IRF3 is the principal positive regulator of IFN-beta production. Reason: Core function; IRF3 is a more potent activator of the IFN-beta gene than IFN-alpha and is essential for IFN-beta enhanceosome assembly. |
| GO:0032728 positive regulation of interferon-beta production | ISS GO_REF:0000024 | ACCEPT | Summary: IRF3 is the principal positive regulator of IFN-beta production. Reason: Core function; IRF3 is a more potent activator of the IFN-beta gene than IFN-alpha and is essential for IFN-beta enhanceosome assembly. |
| GO:0032728 positive regulation of interferon-beta production | TAS PMID:16979567 Type I interferon [corrected] gene induction by the interfer... | ACCEPT | Summary: IRF3 is the principal positive regulator of IFN-beta production. Reason: Core function; IRF3 is a more potent activator of the IFN-beta gene than IFN-alpha and is essential for IFN-beta enhanceosome assembly. |
| GO:0034142 toll-like receptor 4 signaling pathway | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: IRF3 acts downstream of TLR4 (via the TRAM/TRIF branch) to induce type I IFN. Reason: Supported by the shared TRIF-dependent adaptor phosphorylation mechanism of IRF3 recruitment. Supporting Evidence: PMID:25636800 protein in Toll-like receptor signaling, activates IRF3 through a similar |
| GO:0035666 TRIF-dependent toll-like receptor signaling pathway | IDA PMID:25636800 Phosphorylation of innate immune adaptor proteins MAVS, STIN... | ACCEPT | Summary: IRF3 is activated by the TRIF-dependent TLR3/TLR4 signaling branch. Reason: Core pathway; TRIF is phosphorylated on its pLxIS motif to recruit and activate IRF3. Supporting Evidence: PMID:25636800 protein in Toll-like receptor signaling, activates IRF3 through a similar |
| GO:0039530 MDA-5 signaling pathway | TAS PMID:16979567 Type I interferon [corrected] gene induction by the interfer... | ACCEPT | Summary: IRF3 acts downstream of MDA5 (through MAVS) to induce type I IFN. Reason: Consistent with its role as the terminal transcription factor of RLR-MAVS signaling. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:15841462 Interaction between the HCV NS3 protein and the host TBK1 pr... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:16301520 Hepatitis C virus protease NS3/4A cleaves mitochondrial anti... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:18725644 Structural basis for suppression of a host antiviral respons... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:19416887 ISG56 is a negative-feedback regulator of virus-triggered si... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:19454348 Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:20403326 Reconstitution of the RIG-I pathway reveals a signaling role... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:20581830 The transcription factor MafB antagonizes antiviral response... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:21102435 ZAPS is a potent stimulator of signaling mediated by the RNA... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:21782231 MAVS forms functional prion-like aggregates to activate and ... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:22000020 Activation of STAT6 by STING is critical for antiviral innat... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. 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: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:23746807 Structural insights into the functions of TBK1 in innate ant... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:31390091 TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiv... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:32726803 Papain-like protease regulates SARS-CoV-2 viral spread and i... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:34084167 SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Produ... | MODIFY | Summary: Identical protein binding reflects the well-documented phosphorylation-induced IRF3 homodimerization; IRF3 appears in its own WITH/FROM as expected for a self-association assay. Reason: Phospho-IRF3 forms homodimers that are required for activity and are resolved crystallographically, so the underlying biology is sound. But 'identical protein binding' is a generic binding term that does not say what the self-association is, and ACCEPT would retain 17 such rows in the core set. Replace with the precise child GO:0042803 'protein homodimerization activity', which is already annotated to IRF3 and already carried in core_functions - the same treatment the CGAS review in this PR gives the same term. Proposed replacements: protein homodimerization activity |
| GO:0042803 protein homodimerization activity | IDA PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosoli... | ACCEPT | Summary: Phosphorylation-induced IRF3 homodimerization is required for its activation and is documented structurally. Reason: Core structural molecular function of activated IRF3. Supporting Evidence: PMID:22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA |
| GO:0042803 protein homodimerization activity | IDA PMID:30699354 The EF-Hand Protein CALML6 Suppresses Antiviral Innate Immun... | ACCEPT | Summary: Phosphorylation-induced IRF3 homodimerization is required for its activation and is documented structurally. Reason: Core structural molecular function of activated IRF3. |
| GO:0042803 protein homodimerization activity | IPI PMID:12062447 Involvement of TIRAP/MAL in signaling for the activation of ... | ACCEPT | Summary: Phosphorylation-induced IRF3 homodimerization is required for its activation and is documented structurally. Reason: Core structural molecular function of activated IRF3. |
| GO:0042981 regulation of apoptotic process | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | KEEP AS NON CORE | Summary: IRF3 regulates apoptosis through the mitochondrial Tom70/Hsp90/IRF3/Bax complex during viral infection. Reason: A genuine but secondary, non-core function distinct from IRF3's central transcriptional role. Supporting Evidence: PMID:25609812 Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | UNDECIDED | Summary: Positive regulation of canonical NF-kappaB signaling, by electronic ortholog transfer (rat). Reason: IRF3's role in NF-kappaB activation downstream of STING is actively disputed: one report proposes IRF3 acts as a molecular adaptor promoting TRAF6-STING-driven NF-kappaB activation (PMID:40973797) while another shows STING-dependent NF-kappaB activation is IRF3-independent (PMID:41747053). Given the unresolved conflict noted in UniProt, this annotation cannot yet be adjudicated. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:17574024 An atomic model of the interferon-beta enhanceosome. | ACCEPT | Summary: IRF3 binds specific DNA sequences (ISRE/IRF consensus). Reason: Core molecular function established by biochemical and high-throughput DNA-binding-specificity studies. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:23332764 DNA-binding specificities of human transcription factors. | ACCEPT | Summary: IRF3 binds specific DNA sequences (ISRE/IRF consensus). Reason: Core molecular function established by biochemical and high-throughput DNA-binding-specificity studies. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 positively regulates DNA-templated transcription of its targets. Reason: Correct general parent term; more specific Pol II activation terms are also annotated. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:8524823 Identification of a member of the interferon regulatory fact... | ACCEPT | Summary: IRF3 positively regulates RNA polymerase II transcription of type I IFN and interferon-stimulated genes. Reason: Core biological process, supported by direct reporter/target-gene activation and enhanceosome assembly data. Supporting Evidence: PMID:8524823 Overexpression of IRF-3 stimulates expression of the IFN-stimulated gene 15 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:9660935 Virus infection induces the assembly of coordinately activat... | ACCEPT | Summary: IRF3 positively regulates RNA polymerase II transcription of type I IFN and interferon-stimulated genes. Reason: Core biological process, supported by direct reporter/target-gene activation and enhanceosome assembly data. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: IRF3 positively regulates RNA polymerase II transcription of type I IFN and interferon-stimulated genes. Reason: Core biological process, supported by direct reporter/target-gene activation and enhanceosome assembly data. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17560375 Structure of IRF-3 bound to the PRDIII-I regulatory element ... | ACCEPT | Summary: IRF3 positively regulates RNA polymerase II transcription of type I IFN and interferon-stimulated genes. Reason: Core biological process, supported by direct reporter/target-gene activation and enhanceosome assembly data. |
| GO:0051607 defense response to virus | IEA GO_REF:0000120 | ACCEPT | Summary: IRF3 mediates the antiviral defense response by inducing type I IFN. Reason: Correct; a core-adjacent process reflecting IRF3's antiviral role. |
| GO:0051607 defense response to virus | ISS GO_REF:0000024 | ACCEPT | Summary: IRF3 mediates the antiviral defense response by inducing type I IFN. Reason: Correct; a core-adjacent process reflecting IRF3's antiviral role. |
| GO:0060337 type I interferon-mediated signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Type I interferon-mediated signaling pathway (the receptor-triggered, JAK-STAT response), by electronic ortholog transfer. Reason: IRF3 acts UPSTREAM, inducing type I IFN production (GO:0032481); it is not a component of the type I IFN receptor signaling/response cascade (STAT1/STAT2/IRF9). This electronic annotation likely conflates IFN production with IFN response and over-states IRF3's role. |
| GO:0071360 cellular response to exogenous dsRNA | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 is activated in response to cytosolic/exogenous dsRNA (via RIG-I/MDA5 and TLR3). Reason: Consistent with its role as the transcriptional effector of dsRNA sensing. |
| GO:0071888 macrophage apoptotic process | TAS PMID:16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regu... | KEEP AS NON CORE | Summary: Active IRF3 can induce apoptosis (cell death) in primary macrophages. Reason: A genuine but secondary, cell-type-specific pro-apoptotic effect, not IRF3's core transcriptional function. Supporting Evidence: PMID:16846591 form of IRF-3 led to induction of cell death |
| GO:0098586 cellular response to virus | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | ACCEPT | Summary: IRF3 is a central effector of the cellular response to virus infection. Reason: Core-adjacent antiviral process, directly documented. |
| GO:0098586 cellular response to virus | IEA GO_REF:0000120 | ACCEPT | Summary: IRF3 is a central effector of the cellular response to virus infection. Reason: Core-adjacent antiviral process, directly documented. |
| GO:0140896 cGAS/STING signaling pathway | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: IRF3 is the terminal transcription factor of the cGAS/STING cytosolic-DNA sensing pathway. Reason: Core biological process; STING recruits and licenses IRF3 phosphorylation by TBK1. |
| GO:1900017 positive regulation of cytokine production involved in inflammatory response | TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe... | ACCEPT | Summary: IRF3 positively regulates inflammatory cytokine production. Reason: Correct though broad; consistent with IRF3-driven cytokine (type I IFN) induction. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: IRF3 binds double-stranded ISRE/IRF DNA sequences. Reason: Precise, experimentally supported core molecular function. |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: IRF3 binds promoter chromatin at target ISG/IFN genes. Reason: Consistent with its role as a sequence-specific promoter-binding transcription factor; electronic ortholog annotation is acceptable. |
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