IKBKE

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
Identifiers
Symbols	IKBKE ; IKK-E; IKK-i; IKKE; IKKI
External IDs	OMIM: 605048 MGI: 1929612 HomoloGene: 23168 ChEMBL: 3529 GeneCards: IKBKE Gene
EC number	2.7.11.10
Gene ontology Molecular function • NF-kappaB-inducing kinase activity • protein binding • ATP binding • IkappaB kinase activity • ubiquitin protein ligase binding • K48-linked polyubiquitin binding • K63-linked polyubiquitin binding Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol • endosome membrane • PML body • mitochondrial membrane Biological process • toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • immune response • I-kappaB phosphorylation • intrinsic apoptotic signaling pathway in response to DNA damage • negative regulation of type I interferon production • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • response to interferon-beta • TRIF-dependent toll-like receptor signaling pathway • NIK/NF-kappaB signaling • positive regulation of I-kappaB kinase/NF-kappaB signaling • innate immune response • protein homooligomerization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9641	56489
Ensembl	ENSG00000263528	ENSMUSG00000042349
UniProt	Q14164	Q9R0T8
RefSeq (mRNA)	NM_001193321	NM_019777
RefSeq (protein)	NP_001180250	NP_062751
Location (UCSC)	Chr 1: 206.47 – 206.5 Mb	Chr 1: 131.25 – 131.28 Mb
PubMed search

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.^[1][2][3]

Interactions

IKBKE has been shown to interact with TANK.^[4]

Clinical significance

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.^[5]

References

1. Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S (September 1999). "IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases". Int Immunol 11 (8): 1357–62. doi:10.1093/intimm/11.8.1357. PMID 10421793.
2. Peters RT, Liao SM, Maniatis T (July 2000). "IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex". Mol Cell 5 (3): 513–22. doi:10.1016/S1097-2765(00)80445-1. PMID 10882136.
3. "Entrez Gene: IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon".
4. Nomura F, Kawai T, Nakanishi K, Akira S (March 2000). "NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation". Genes Cells 5 (3): 191–202. doi:10.1046/j.1365-2443.2000.00315.x. PMID 10759890.
5. Llona-Minguez S, Baiget J, Mackay S P, (2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases". Pharm. Pat. Anal. 2 (4): 481–498. doi:10.4155/ppa.13.31. PMID 24237125.

Further reading

• Mercurio AM (2003). "Invasive skin carcinoma--Ras and alpha6beta4 integrin lead the way.". Cancer Cell 3 (3): 201–2. doi:10.1016/S1535-6108(03)00049-7. PMID 12676577.
• Nagase T, Seki N, Tanaka A, et al. (1996). "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1.". DNA Res. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.
• Nomura F, Kawai T, Nakanishi K, Akira S (2000). "NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation.". Genes Cells 5 (3): 191–202. doi:10.1046/j.1365-2443.2000.00315.x. PMID 10759890.
• Miller BS, Zandi E (2001). "Complete reconstitution of human IkappaB kinase (IKK) complex in yeast. Assessment of its stoichiometry and the role of IKKgamma on the complex activity in the absence of stimulation.". J. Biol. Chem. 276 (39): 36320–6. doi:10.1074/jbc.M104051200. PMID 11470787.
• Kishore N, Huynh QK, Mathialagan S, et al. (2002). "IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2.". J. Biol. Chem. 277 (16): 13840–7. doi:10.1074/jbc.M110474200. PMID 11839743.
• Aupperle KR, Yamanishi Y, Bennett BL, et al. (2002). "Expression and regulation of inducible IkappaB kinase (IKK-i) in human fibroblast-like synoviocytes.". Cell. Immunol. 214 (1): 54–9. doi:10.1006/cimm.2002.1885. PMID 11902829.
• Bossis G, Salinas S, Cartier C, et al. (2002). "NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases.". FEBS Lett. 516 (1-3): 257–64. doi:10.1016/S0014-5793(02)02566-8. PMID 11959143.
• Chariot A, Leonardi A, Muller J, et al. (2002). "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.". J. Biol. Chem. 277 (40): 37029–36. doi:10.1074/jbc.M205069200. PMID 12133833.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Fitzgerald KA, McWhirter SM, Faia KL, et al. (2003). "IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.". Nat. Immunol. 4 (5): 491–6. doi:10.1038/ni921. PMID 12692549.
• Kravchenko VV, Mathison JC, Schwamborn K, et al. (2003). "IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli.". J. Biol. Chem. 278 (29): 26612–9. doi:10.1074/jbc.M303001200. PMID 12736252.
• Matsuda A, Suzuki Y, Honda G, et al. (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.". Oncogene 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
• Fujita F, Taniguchi Y, Kato T, et al. (2003). "Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling.". Mol. Cell. Biol. 23 (21): 7780–93. doi:10.1128/MCB.23.21.7780-7793.2003. PMC 207563. PMID 14560022.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
• tenOever BR, Sharma S, Zou W, et al. (2004). "Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity.". J. Virol. 78 (19): 10636–49. doi:10.1128/JVI.78.19.10636-10649.2004. PMC 516426. PMID 15367631.
• Buss H, Dörrie A, Schmitz ML, et al. (2005). "Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription.". J. Biol. Chem. 279 (53): 55633–43. doi:10.1074/jbc.M409825200. PMID 15489227.