Reveal
Gene
CHUK
Uniprot
O15111
Protein
Inhibitor of nuclear factor kappa-B kinase subunit alpha
See alternative names Conserved helix-loop-helix ubiquitous kinase,
I-kappa-B kinase 1,
Nuclear factor NF-kappa-B inhibitor kinase alpha,
Transcription factor 16
Uniprot Function Description
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:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576, PubMed:35952808). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). 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:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973).
Sample type
Human EDTA plasma and serum are the recommended sample types. Human citrate plasma and heparin plasma are also accepted. For other samples types e.g cerebrospinal fluid, (CSF), tissue or cell lysates please we recommend Olink Target 96 panels. Please note that protein expression levels are expected to vary in different sample types and certain assays may be affected by interfering substances such as hemolysate.
Precision
Precision (repeatability) is calculated from linearized NPX values over LOD.
Analytical measuring range
The technical data reported below refers to the measured value in the in vitro validation assays run using known concentrations of recombinant antigen. Please note that these figures are for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples.
Dilution factor
For optimal assay readout, Olink Explore is run using different dilutions of the original samples (undiluted, 1:10, 1:100 or 1:1000). The dilution factor for this assay is noted below and should be taken into account when estimating the appropriate addressable biological concentration of the protein based on the in vitro validation data.
Sensitivity plot
The calibrator curve shown below visualizes the analytical measuring range data based on in vitro measurement of recombinant antigen. Please note that this is shown for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples. The vertical dotted lines represent LLOQ and ULOQ respectively, and the horizontal line indicates the LOD.
Sample distribution plot
The plot below shows the levels of protein measured in a number of commercial plasma samples. Healthy subjects are shown in blue and samples obtained from patients with a range of diseases are shown in red. The latter include inflammatory, cardiovascular, autoimmune & neurological diseases, as well as cancer. The data is shown to give a general idea of the sort of data range to expect, but cannot cover all potential levels that may be seen in clinical samples.
Biomarker Validation Data
Additional validation data, as well as a more detailed description of how the Olink panels are quality controlled can be found in our Data Validation documents – go to Document download center