Recombinant Human IKK beta protein

Specifications

Form

Liquid

General info

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 (PubMed : 20434986, PubMed : 20797629, PubMed : 21138416, PubMed : 30337470, PubMed : 9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed : 9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed : 20434986, PubMed : 20797629, PubMed : 21138416, PubMed : 9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed : 20434986, PubMed : 20797629, PubMed : 21138416, PubMed : 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 apoptosis (PubMed : 20434986, PubMed : 20797629, PubMed : 21138416, PubMed : 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 IKBKE (PubMed : 11297557, PubMed : 14673179, PubMed : 20410276, PubMed : 21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed : 11297557, PubMed : 20410276, PubMed : 21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed : 15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed : 17213322, PubMed : 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 nucleus (PubMed : 25326418). 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 (PubMed : 38621137). 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 (PubMed : 32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed : 32209697).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Post-translational modifications

Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity (PubMed:10022904, PubMed:16207722). Phosphorylated by MAP3K7/TAK1 in response to NOD1 and NOD2 signaling, promoting activation and phosphorylation of NF-kappa-B inhibitors, leading to NF-kappa-B activation (PubMed:11460167). Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response (PubMed:10195894). Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription (PubMed:10783893). Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B (PubMed:18930133).. (Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.. Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to PubMed:19675099, 'Ser-163' does not serve as a monoubiquitination site. According to PubMed:16267042, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues.. (Microbial infection) Monoubiquitination by TRIM21 is disrupted by Yersinia YopJ.. Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.

Subcellular localisation

Nucleus