Summary

Name IKBKE
Full Name Inhibitor of nuclear factor kappa-B kinase subunit epsilon
Synonyms I-kappa-B kinase epsilon, IKK-E, IKK-epsilon, IkBKE, Inducible I kappa-B kinase, IKK-i | IKKE, IKKI, KIAA0151
Primary ID Q14164
Links - -
Type protein
Relations 37
Pathways COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
Inhibitors N-[3-[[5-iodo-4-[3-[[oxo(thiophen-2-yl)methyl]amino]propylamino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide
Function 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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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation TANK 0.733
Publications: 9 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.346
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRAF3IP2 0.426
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKBIA 0.501
Publications: 2 Organism: , Homo Sapiens
Pathways:COVID-19 Causal Network, Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation IRF3 0.732
Publications: 7 Organism: In Vitro
Pathways:COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
+ img/unknown.png phosphorylation CDK2AP1 0.2
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation RELA 0.453
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IRF7 0.674
Publications: 2 Organism: Homo Sapiens
Pathways:Innate Immune Response
+ down-regulates img/direct_inhibition.png phosphorylation FOXO 0.422
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXO3 0.422
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT1 0.414
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding IKBKE 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition IKBKE 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NfKb-p65/p50 0.436
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
+ down-regulates activity img/direct_inhibition.png binding IKBKE 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV INNATE RESPONSE TO dsRNA
+ up-regulates activity img/direct-activation.png binding IKBKE 0.824
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA
+ up-regulates activity img/direct-activation.png binding IKBKE 0.622
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
+ up-regulates img/direct-activation.png phosphorylation REL/RELA 0.409
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TBK1 0.622
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
+ up-regulates img/direct-activation.png phosphorylation REL 0.365
Publications: 1 Organism: Homo Sapiens