UniprotKB/SwissProt ID: O88351 (O88351)
Gene Name:
Ikbkb
Organism: Mus musculus (Mouse)
Function: Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (By similarity). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (By similarity). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (By similarity). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (By similarity). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (By similarity). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (By similarity). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (By similarity). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (By similarity). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (By similarity). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (PubMed:30988283). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326420). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-748' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-748' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (By similarity). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (By similarity)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Cytoplasm. Nucleus. Membrane raft
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