Homo sapiens Protein: IKBKB
InnateDB Protein IDBP-369376.5
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 ENSP00000404920
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.
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
RNA-RNA 1 [view]
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: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: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:0035631 CD40 receptor complex
GO:0045121 membrane raft
Protein Structure and Domains
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
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
Post-translational Modifications
SwissProt O14920
PhosphoSite PhosphoSite-O14920
UniProt Splice Variant
Entrez Gene 3551
UniGene Hs.715799
RefSeq NP_001229707
OMIM 603258
HPRD 04462
EMBL AC083973 AF029684 AF031416 AF080158 AK302723 AK303528 AK316418 AY663108 BC006231
GenPept AAC51860 AAC64675 AAD08997 AAH06231 AAT65965 BAG63942 BAG64556 BAH14789