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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 .
PMID:20434986 PMID:20797629 PMID:21138416 PMID:30337470 PMID:9346484

Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation .
PMID:9346484
Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues .
PMID:20434986 PMID:20797629 PMID:21138416 PMID:9346484

These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome .
PMID:20434986 PMID:20797629 PMID:21138416 PMID: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 .
PMID:20434986 PMID:20797629 PMID:21138416 PMID: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 .
PMID:11297557 PMID:14673179 PMID:20410276 PMID:21138416

IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs .
PMID:11297557 PMID:20410276 PMID:21138416

Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor .
PMID:15084260
Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 .
PMID:17213322 PMID: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 .
PMID: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 .
PMID: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 .
PMID:32209697
It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription PMID:32209697

Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity .
PMID:17920186 PMID:19755138
Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Involved in morula development (2-16 cells embryos) by acting as a regulator at the 8-cell stage (By similarity). Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells.

Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 .
PMID:23836911
Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity .
PMID:17920186 PMID:19755138
During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation.

This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)

Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter.

Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle