InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IKBKB

Summary

InnateDB Protein

IDBP-477372.4

Last Modified

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

Gene Symbol

IKBKB

Protein Name

inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta

Synonyms

IKK-beta; IKK2; IKKB; IMD15; NFKBIKB;

Species

Homo sapiens

Ensembl Protein

ENSP00000430868

InnateDB Gene

IDBG-19987 (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. {ECO:0000269PubMed:11297557, ECO:0000269PubMed:17213322, ECO:0000269PubMed:19716809, ECO:0000269PubMed:20410276, ECO:0000269PubMed:20434986, ECO:0000269PubMed:20797629, ECO:0000269PubMed:21138416}.

Subcellular Localization

Cytoplasm. Nucleus. Membrane raft. Note=Colocalized with DPP4 in membrane rafts.

Disease Associations

Immunodeficiency 15 (IMD15) [MIM:615592]: An autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T- cells, and impaired differentiation and activation of immune cells. {ECO:0000269PubMed:24369075}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 300 experimentally validated interaction(s) in this database.
They are also associated with 42 interaction(s) predicted by orthology.

Experimentally validated
Total	300 [view]
Protein-Protein	297 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	42 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	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:0019901	protein kinase binding
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity
GO:0097110	scaffold protein binding

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007252	I-kappaB phosphorylation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0009615	response to virus
GO:0032481	positive regulation of type I interferon production
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0042501	serine phosphorylation of STAT protein
GO:0043066	negative regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050852	T cell receptor signaling pathway
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0071356	cellular response to tumor necrosis factor

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0008385	IkappaB kinase complex
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

InterPro

IPR000626 Ubiquitin-like
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR022007 I-kappa-kinase-beta NEMO binding domain
IPR029071 Ubiquitin-related domain

PFAM

PF00240
PF14560
PF00069
PF07714
PF06293
PF12179

PRINTS

PR00109

PIRSF

SMART

SM00213
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt