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Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18836453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22412986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32433612"}],"value":"Maintained as a monomer in an autoinhibited state (PubMed:18836453, PubMed:22412986, PubMed:25326418). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (PubMed:32433612). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326418, PubMed:32433612)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33440148"}],"value":"(Microbial infection) Activated upon coronavirus SARS-CoV-2 infection"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P56477"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18836453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32433612"}],"value":"Homodimer, when phosphorylated (PubMed:18836453, PubMed:25326418). Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (PubMed:32433612). Interacts with MYD88 and TRAF6 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"Q92793","geneName":"CREBBP","intActId":"EBI-81215"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"Q13568","geneName":"IRF5","intActId":"EBI-3931258"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"Q7Z434","geneName":"MAVS","intActId":"EBI-995373"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"Q04206","geneName":"RELA","intActId":"EBI-73886"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"O43765","geneName":"SGTA","intActId":"EBI-347996"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13568","intActId":"EBI-3931258"},"interactantTwo":{"uniProtKBAccession":"Q13263","geneName":"TRIM28","intActId":"EBI-78139"},"numberOfExperiments":5,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12138184"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15556946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15695821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22412986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"}],"value":"Shuttles between the nucleus and the cytoplasm: upon activation by the TLR adapter MYD88 and subsequent phosphorylation, translocates to the nucleus"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12138184"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15556946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15695821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22412986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12138184"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15556946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15695821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22412986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q13568-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q13568-2"],"sequenceIds":["VSP_041375"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q13568-3"],"sequenceIds":["VSP_043924"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q13568-4"],"sequenceIds":["VSP_043925"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q13568-5"],"sequenceIds":["VSP_044822"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"isoformIds":["Q13568-6"],"sequenceIds":["VSP_053330","VSP_053331"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15695821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18836453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22412986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40639948"}],"value":"Phosphorylation of serine and threonine residues by IKBKB in a C-terminal autoinhibitory region, stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/EP300 and initiation of transcription. Phosphorylation at Thr-265 by STK25 induces IRF5 transcriptional activation (PubMed:40639948)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18824541"}],"value":"'Lys-63'-linked polyubiquitination by TRAF6 is required for activation"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Inflammatory bowel disease 14","diseaseAccession":"DI-02656","acronym":"IBD14","description":"A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.","diseaseCrossReference":{"database":"MIM","id":"612245"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17881657"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Systemic lupus erythematosus 10","diseaseAccession":"DI-02652","acronym":"SLEB10","description":"A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. 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