CHUK
UniProt ID: O15111
Entrez ID: 1147
Protein name: Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16)
External links: UniprotKB HGNC RefSeq COSMIC
Please click HERE
for better display.
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:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). Acts ...
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: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). 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). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}.
View more >>
GO - Biological processes (BP):
anatomical structure morphogenesis [GO:0009653]; cellular response to cadmium ion [GO:0071276]; cellular response to reactive oxygen species [GO:0034614]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to virus [GO:0098586]; I-kappaB kinase/NF-kappaB signaling [GO:0007249...
anatomical structure morphogenesis [GO:0009653]; cellular response to cadmium ion [GO:0071276]; cellular response to reactive oxygen species [GO:0034614]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to virus [GO:0098586]; I-kappaB kinase/NF-kappaB signaling [GO:0007249]; I-kappaB phosphorylation [GO:0007252]; immune response [GO:0006955]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; NIK/NF-kappaB signaling [GO:0038061]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123]; positive regulation of interferon-alpha production [GO:0032727]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein phosphorylation [GO:0006468]; response to virus [GO:0009615]; tumor necrosis factor-mediated signaling pathway [GO:0033209]
View more >>
GO - Molecular function (MF):
ATP binding [GO:0005524]; IkappaB kinase activity [GO:0008384]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; protein kinase activity [GO:0004672]; protein serine/threonine kinase activity [GO:0004674]; scaffold protein binding [GO:0097110]; transf...
ATP binding [GO:0005524]; IkappaB kinase activity [GO:0008384]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; protein kinase activity [GO:0004672]; protein serine/threonine kinase activity [GO:0004674]; scaffold protein binding [GO:0097110]; transferrin receptor binding [GO:1990459]
View more >>
GO - Cellular component (CC):
CD40 receptor complex [GO:0035631]; cytoplasm [GO:0005737]; cytoplasmic side of plasma membrane [GO:0009898]; cytosol [GO:0005829]; IkappaB kinase complex [GO:0008385]; nucleoplasm [GO:0005654]...
CD40 receptor complex [GO:0035631]; cytoplasm [GO:0005737]; cytoplasmic side of plasma membrane [GO:0009898]; cytosol [GO:0005829]; IkappaB kinase complex [GO:0008385]; nucleoplasm [GO:0005654]
View more >>
CHUK
Control panel
Show dataset:
Show Degron:
All sites
Degron
Degron
Filter mutation sites
All sites
Minimum 5 samples
Minimum 10 samples
Minimum 5 samples
Minimum 10 samples
Data table is loading....
Kaplan plot for CHUK in
Download patient class data (Lower:Upper = 50%:50%)
*NOTE: the Kaplan plots were collected from OncoLnc