InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ikbke

Summary

InnateDB Protein

IDBP-190985.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Ikbke

Protein Name

inhibitor of kappaB kinase epsilon

Synonyms

AW558201; IKK-i; IKKepsilon; Ikki;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000054126

InnateDB Gene

IDBG-190983 (Ikbke)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15210742, ECO:0000269PubMed:17332413, ECO:0000269PubMed:19737522, ECO:0000269PubMed:22065572, ECO:0000269PubMed:22171011, ECO:0000269PubMed:23396211}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Note=Targeting to PML nuclear bodies upon DNA damage is TOPORS-dependent. {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in bone marrow-derived macrophages and at low levels in liver and white adipose tissue (at protein level). Detected in muscle and lung. {ECO:0000269PubMed:17332413, ECO:0000269PubMed:19737522, ECO:0000269PubMed:23396211}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 333 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	2 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	333 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004704	NF-kappaB-inducing kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008384	IkappaB kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0007252	I-kappaB phosphorylation
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0038061	NIK/NF-kappaB signaling
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0016605	PML body

Protein Structure and Domains

PDB ID

MGI:1929612

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt