Tchem IKBKE Inhibitor of nuclear factor kappa-B kinase subunit epsilon

Protein Summary

Description

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. 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]).[supplied by OMIM, Oct 2009]

Uniprot Accession IDs

• Q14164
• D3DT78
• Q3B754
• Q3KR43
• Q5JTS6
• I-kappa-B kinase epsilon

Gene Name

• IKBKE

Ensembl ID

• ENST00000581977
• ENSP00000464030
• ENSG00000263528
• ENST00000584998
• ENSP00000462396

Symbol

• IKKE
• IKKI
• KIAA0151
• IKKE
• IKKI
• IKK-E
• IKK-i

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	1
hub protein	1
co-expressed gene	0.97
molecular function	0.97
interacting protein	0.91

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Inhibitor Of Nuclear Factor Kappa-b Kinase Subunit Epsilon

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Ikk Family / Inhibitor Of Nuclear Factor Kappa-b Kinase Subunit Epsilon

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 78.73   (req: < 5)

Gene RIFs: 120   (req: <= 3)

Antibodies: 533   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 78.73   (req: >= 5)

Gene RIFs: 120   (req: > 3)

Antibodies: 533   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 21

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 71

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1