IKBKB — Inhibitor of nuclear factor kappa B kinase subunit beta
IKBKB belongs to a gene co-expression module in 3 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
IKBKB's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | T cell exhaustion Exhaustion | CD247, CD38, CD59, FLT1, GAN, LAG3, LRBA, PTMS +3 more | View in SCUBA |
| Endothelial | NF-kB Chromatin Regulation DNA/chromatin regulation | ARHGEF3, DGKE, HLA-E, HOXB3, ITPKB, KITLG, LIMCH1, MALT1 +4 more | View in SCUBA |
| Macrophages | Post-transcriptional Regulation Housekeeping | AKAP10, ATF7IP, ATRN, ATXN2, BAZ2B, BLTP1, BRWD1, CELF2 +34 more | View in SCUBA |
About the gene
| Synonyms | IKK-beta, IKK2, IKKB, NFKBIKB |
|---|---|
| Chromosome | 8: 42271302-42332460 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins |
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Host-virus interaction |
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 a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. 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. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF- mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus. Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses. IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6. It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.