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 (  ). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation . Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues ( , ). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome ( , ). 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 ( , ). 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 ( , ). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs ( ). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor . Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (, ). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus .
Subcellular locations: Cytoplasm, Nucleus, Membrane raft
Colocalized with DPP4 in membrane rafts.
Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.