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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)
End	206,496,889 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	131,207,344 bp
RNA expression pattern
	Top expressed in
	epithelium of colon; ; granulocyte; ; monocyte; ; blood; ; lymph node; ; bone marrow cells; ; appendix; ; mucosa of esophagus; ; tonsil; ; mucosa of transverse colon;
	Top expressed in
	mesenteric lymph nodes; ; crypt of lieberkuhn of small intestine; ; thymus; ; stroma of bone marrow; ; granulocyte; ; jejunum; ; duodenum; ; ileum; ; blood; ; choroidal fissure;
	More reference expression data
	; ;
	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
	9641
	56489
	ENSG00000263528
	ENSMUSG00000042349
	Q14164
	Q9R0T8
	NM_001193321; NM_001193322; NM_014002
	NM_019777
	NP_001180250; NP_001180251; NP_054721
	NP_062751
	Wikidata
View/Edit Human	View/Edit Mouse

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]

Interactions

IKBKE has been shown to interact with TANK.^[8]

Function

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]

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.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000263528 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000042349 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ "Entrez Gene: IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon".
^ 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. S2CID 8489218.
^ "Inhibitor of nuclear factor kappa-B kinase subunit epsilon". {{cite journal}}: Cite journal requires |journal= (help)
^ Llona-Minguez S, Baiget J, Mackay SP (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.