a kinase of the IKK family. Phosphorylates inhibitors of NF-kappa-B, leading to their dissociation from NF-kappa-B and ultimately to their degradation. Phosphorylated and activated downstream of growth factor receptors, IL1R, and TNFR by NAK, IRAK and NIK, respectively. Preferentially found as a heterodimer with IKK-beta but also as an homodimer. Directly interacts with IKK-gamma/NEMO and TRPC4AP. Heterodimers form the active complex. The tripartite complex can also bind to MAP3K14/NIK, MEKK1, IKAP and IKB-alpha-p65-p50 complex. Inhibitors are under development to treat arthritis, inflammation, and apoptotic aspects of cancer. Aspirin (sodium salicylate) selectively binds IKK and reduces inflammation. Misexpression and inhibitors show involvement in insulin sensitization in obese rodents. Mutations in IKK-gamma are found in several immune deficiencies: hyper IgM syndrome, incontinentia pigmenti [embryonic lethal in males, defects in skin, hair, teeth in females] and hypohidrotic ectodermal dysplasia; recurrent infections and defects in teeth, hair, and sweat glands]. Inhibitors: CHS 828, NBD peptide, BMS-345541. Note: This description may include information from UniProtKB.
Protein type: EC 126.96.36.199; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; Protein kinase, Other; Other group; IKK family
Cellular Component: internal side of plasma membrane; intracellular membrane-bound organelle; cytoplasm; nucleolus; IkappaB kinase complex; cytosol; nucleus
Molecular Function: protein binding; protein homodimerization activity; IkappaB kinase activity; protein heterodimerization activity; ATP binding; protein kinase activity
Biological Process: lactation; skeletal muscle contraction; I-kappaB kinase/NF-kappaB cascade; nerve growth factor receptor signaling pathway; response to toxin; response to lipopolysaccharide; osteoclast differentiation; toll-like receptor 3 signaling pathway; T cell receptor signaling pathway; protein amino acid phosphorylation; Rho protein signal transduction; activation of NF-kappaB transcription factor; toll-like receptor 10 signaling pathway; toll-like receptor 5 signaling pathway; morphogenesis of an epithelial sheet; positive regulation of interferon type I production; inflammatory response; toll-like receptor 4 signaling pathway; response to drug; epidermal growth factor receptor signaling pathway; anatomical structure morphogenesis; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB cascade; response to virus; MyD88-independent toll-like receptor signaling pathway; mammary gland epithelial cell proliferation; response to amino acid stimulus; odontogenesis of dentine-containing teeth; toll-like receptor 2 signaling pathway; MyD88-dependent toll-like receptor signaling pathway; response to hydroperoxide; toll-like receptor signaling pathway; innate immune response; striated muscle cell differentiation; immune response; positive regulation of transcription from RNA polymerase II promoter; toll-like receptor 9 signaling pathway; I-kappaB phosphorylation
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.