Recombinant Human Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)

Uniprot Id

Q14164

Target Species

Human

Target Name

IKBKE

Target Full Name

Inhibitor of nuclear factor kappa-B kinase subunit epsilon

Target 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.

Target Subcellular Location

Cytoplasm. Nucleus. Nucleus, PML body.

Target Protein Families

Protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily

Target Tissue Specificity

Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon.

Target Synonyms

I kappa B kinase epsilon; I-kappa-B kinase epsilon; IkBKE; IKK related kinase epsilon; IKK-E; IKK-epsilon; IKK-i; IKKE; IKKE_HUMAN; IKKepsilon; IKKI; Inducible I kappa B kinase; Inducible I kappa-B kinase; Inducible IkappaB kinase; Inhibitor of kappa light polypeptide gene enhancer in B cells kinase epsilon; Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase of, epsilon; Inhibitor of nuclear factor kappa-B kinase subunit epsilon; KIAA0151; MGC125294; MGC125295; MGC125297

Target Background

IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).