Inhibitor of nuclear factor kappa-B kinase subunit beta

Inhibitor of nuclear factor kappa-B kinase subunit beta

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 stresses20434986,20797629,21138416,30337470,9346484. Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation9346484. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues20434986,20797629,21138416,9346484. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome20434986,20797629,21138416,9346484. 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 apoptosis20434986,20797629,21138416,9346484. 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 IKBKE11297557,14673179,20410276,21138416. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs11297557,20410276,21138416. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor15084260. Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS117213322,19716809. 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 nucleus25326418. Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses38621137. 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 IL632209697. It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription32209697

Quoted from UniProt’s FUNCTION annotation for O14920 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Cytosol

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm · Nucleus · Membrane raft