IKKE Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; IKK family; Inhibitor; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of human Ortholog: 1q32.1
Cellular Component:  cytoplasm; cytosol; mitochondrial membrane; nucleoplasm; nucleus; PML body; serine/threonine protein kinase complex
Molecular Function:  ATP binding; identical protein binding; IkappaB kinase activity; K48-linked polyubiquitin modification-dependent protein binding; K63-linked polyubiquitin modification-dependent protein binding; NF-kappaB-inducing kinase activity; protein binding; protein phosphatase binding; protein serine/threonine kinase activity; ubiquitin protein ligase binding
Biological Process:  cellular response to virus; defense response to virus; gene expression; I-kappaB phosphorylation; immune response; interleukin-17-mediated signaling pathway; intrinsic apoptotic signaling pathway in response to DNA damage; mRNA stabilization; NIK/NF-kappaB signaling; peptidyl-serine phosphorylation; positive regulation of DNA-binding transcription factor activity; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of lipid storage; positive regulation of type I interferon-mediated signaling pathway; protein phosphorylation; regulation of protein-containing complex assembly; response to interferon-beta; type I interferon-mediated signaling pathway
Reference #:  Q14164 (UniProtKB)
Alt. Names/Synonyms: I-kappa-B kinase epsilon; IKBKE; IKK-E; IKK-epsilon; IKK-i; IKK-related kinase epsilon; IKKE; IKKI; Inducible I kappa-B kinase; inducible IkappaB kinase; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon; inhibitor of nuclear factor kappa B kinase subunit epsilon; Inhibitor of nuclear factor kappa-B kinase subunit epsilon; KIAA0151; MGC125294; MGC125295; MGC125297
Gene Symbols: IKBKE
Molecular weight: 80,462 Da
Basal Isoelectric point: 7.91  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  Death Receptor Signaling  |  NF-kB Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein