Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

IKBKE (Q14164) - Overview - Molecular Target Synopsis

Protein


IKBKE, Inhibitor of nuclear factor kappa-B kinase subunit epsilon
Enzyme Classification 2.7.11.10
UniProt Q14164

Also Known as IKKE_HUMAN, IKBKE, IKKE, IKKI, KIAA0151

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. Homodimer. Interacts with MAVS/IPS1. Interacts with the adapter proteins AZI2/NAP1, TANK and TBKBP1/SINTBAD. Interacts with SIKE1. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I; interactions are disrupted by the interaction between IKBKE and SIKE1. Interacts with TOPORS; induced by DNA damage. Interacts with CYLD. Interacts (when polyubiquitinated) with IKBKB, IKBKG and MYD88. Interacts with IFIH1 (PubMed:17600090). Interacts with DDX3X; the interaction is found to be induced upon virus infection. Interacts with TRIM6 (via SPRY box) (PubMed:24882218). Interacts with unanchored K48-linked polyubiquitin chains; this leads to IKBKE activation (PubMed:24882218).

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
716ENSG00000143466ENST00000367120ENSP00000356087Q14164-1
631ENSG00000143466ENST00000537984ENSP00000444529Q14164-2

Sub-cellular localization


UniProt: IKBKE is active in the following subcellular-locations: cytoplasm, nucleus, pml body.
GO terms: IKBKE is active in the following subcellular-locations: cytoplasm, cytosol, endosome membrane, mitochondrial membrane, nucleoplasm, nucleus, PML body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project IKBKE has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: DU_145, LOXIMVI, HOP_92

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: EPLC-272H, COV413A, CAL-12T

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, IMR-90, HUVEC

(see details)

3D Structures


At greater than 50% identity similarity to IKBKE there are:
20 structures (24 chains) solved
20 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

IKBKE is solved in complex with the approved drug(s):

ANW/AMLEXANOX (5W5V_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


IKBKE has been screened with 1000 compounds (2114 bioactivities), 228 compounds have bioactivities that show binding affinity of <= 500nM (242 bioactivities). (see details)