InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ikbkb

Summary

InnateDB Protein

IDBP-141025.7

Last Modified

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

Gene Symbol

Ikbkb

Protein Name

inhibitor of kappaB kinase beta

Synonyms

AI132552; IKK-2; IKK-beta; IKK[b]; IKK2; IKKbeta;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000064235

InnateDB Gene

IDBG-141021 (Ikbkb)

Protein Structure

UniProt Annotation

Function

Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Membrane raft {ECO:0000250}. Note=Colocalized with DPP4 in membrane rafts. {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in liver, kidney and spleen.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 75 experimentally validated interaction(s) in this database.
They are also associated with 169 interaction(s) predicted by orthology.

Experimentally validated
Total	75 [view]
Protein-Protein	72 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	169 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0004672	protein kinase activity
GO:0004702	receptor signaling protein serine/threonine 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
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity
GO:0097110	scaffold protein binding

Biological Process

GO:0001782	B cell homeostasis
GO:0006468	protein phosphorylation
GO:0007252	I-kappaB phosphorylation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0010765	positive regulation of sodium ion transport
GO:0023014	signal transduction by phosphorylation
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0071356	cellular response to tumor necrosis factor
GO:2001259	positive regulation of cation channel activity

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0009898	cytoplasmic side of plasma membrane
GO:0016020	membrane
GO:0035631	CD40 receptor complex
GO:0045121	membrane raft

Protein Structure and Domains

PDB ID

MGI:1338071

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR010978 tRNA-binding arm
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR022007 I-kappa-kinase-beta NEMO binding domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714
PF06293
PF12179

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt