Human Inhibitor of KB kinase Beta,IKKB ELI

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:30337470).

Acts as 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 (PubMed:11297557, PubMed:20410276).

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 (PubMed:15084260).

Also phosphorylates other substrates including NCOA3, BCL10 and IRS1 (PubMed:17213322).

Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation (PubMed:11297557).

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).

{ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470}.