Inhibitor of nuclear factor kappa-B kinase subunit epsilon also known as I-kappa-B kinase epsilon or IKK-epsilon is an enzyme that in humans is encoded by the IKBKE gene.^[5][6][7]

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IKBKE
Identifiers
Aliases	IKBKE, IKK-E, IKK-i, IKKE, IKKI, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon, inhibitor of nuclear factor kappa B kinase subunit epsilon
External IDs	OMIM: 605048; MGI: 1929612; HomoloGene: 23168; GeneCards: IKBKE; OMA:IKBKE - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.1 Start 206,470,476 bp[1] End 206,496,889 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 E4 Start 131,182,080 bp[2] End 131,207,344 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood lymph node bone marrow cells appendix thymus spleen stromal cell of endometrium palpebral conjunctiva rectum Top expressed in crypt of lieberkuhn of small intestine thymus jejunum duodenum ileum blood spleen large intestine colon liver More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity IkappaB kinase activity nucleotide binding K48-linked polyubiquitin modification-dependent protein binding kinase activity protein serine/threonine kinase activity NF-kappaB-inducing kinase activity K63-linked polyubiquitin modification-dependent protein binding protein binding ATP binding ubiquitin protein ligase binding protein kinase activity protein phosphatase binding Cellular component cytoplasm cytosol PML body mitochondrial membranes endosome membrane nucleus nucleoplasm Biological process cellular response to virus phosphorylation I-kappaB phosphorylation response to interferon-beta cellular response to DNA damage stimulus TRIF-dependent toll-like receptor signaling pathway protein phosphorylation response to type I interferon immune response intrinsic apoptotic signaling pathway in response to DNA damage positive regulation of I-kappaB kinase/NF-kappaB signaling negative regulation of type I interferon production protein homooligomerization NIK/NF-kappaB signaling positive regulation of lipid storage peptidyl-serine phosphorylation innate immune response viral process positive regulation of type I interferon-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9641 56489 Ensembl ENSG00000263528 ENSMUSG00000042349 UniProt Q14164 Q9R0T8 RefSeq (mRNA) NM_001193321 NM_001193322 NM_014002 NM_019777 RefSeq (protein) NP_001180250 NP_001180251 NP_054721 NP_062751 Location (UCSC) Chr 1: 206.47 – 206.5 Mb Chr 1: 131.18 – 131.21 Mb PubMed search [3] [4]
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IKBKE has been shown to interact with TANK.^[8]

It is a 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 (TANK-binding kinase 1-binding protein 1) 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 (gamma-activation factor) (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, which leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.^[9]

Inhibition of IκB kinase (IKK) and IKK-related kinases, IKBKE (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.^[10]