IKBKE
Entrez ID: 9641
Full name: inhibitor of nuclear factor kappa B kinase subunit epsilon
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: Other: IKK
Chromosomal location: 1q32.1
Substructure location: Gatekeeper: 86 A-loop: [N/A] G-loop: [N/A] αC-helix: [N/A]
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IKBKE
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 se...
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.
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GO - Biological processes (BP):
cellular response to virus, immune response, intrinsic apoptotic signaling pathway in response to DNA damage, negative regulation of type I interferon production, peptidyl-serine phosphorylation, positive regulation of I-kappaB kinase/NF-kappaB signaling, positive regulation of lipid storage, positi...
cellular response to virus, immune response, intrinsic apoptotic signaling pathway in response to DNA damage, negative regulation of type I interferon production, peptidyl-serine phosphorylation, 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, response to interferon-beta, response to type I interferon, TRIF-dependent toll-like receptor signaling pathway, viral process
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GO - Molecular function (MF):
ATP binding, identical protein binding, IkappaB kinase activity, K48-linked polyubiquitin modification-dependent protein binding, NF-kappaB-inducing kinase activity, protein kinase activity, protein phosphatase binding, protein serine/threonine kinase activity, ubiquitin protein ligase binding...
ATP binding, identical protein binding, IkappaB kinase activity, K48-linked polyubiquitin modification-dependent protein binding, NF-kappaB-inducing kinase activity, protein kinase activity, protein phosphatase binding, protein serine/threonine kinase activity, ubiquitin protein ligase binding
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GO - Cellular component (CC):
cytosol, endosome membrane, mitochondrial membrane, nucleoplasm, nucleus, PML body, cytoplasm...
cytosol, endosome membrane, mitochondrial membrane, nucleoplasm, nucleus, PML body, cytoplasm
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inhibitor of nuclear factor kappa B kinase subunit epsilon
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Kaplan plot for IKBKE in
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*NOTE: the Kaplan plots were collected from OncoLnc