Summary

Name CHUK
Full Name Inhibitor of nuclear factor kappa-B kinase subunit alpha
Synonyms I-kappa-B kinase alpha, IKK-A, IKK-alpha, IkBKA, IkappaB kinase, 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 | IKKA, TCF16
Primary ID O15111
Links - -
Type protein
Relations 63
Pathways NF-KB Non Canonical
Inhibitors N'-(1,8-dimethyl-4-imidazo[1,2-a]quinoxalinyl)ethane-1,2-diamine
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. 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. 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. 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). 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. 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. 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. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:12789342, PubMed:15084260, PubMed:17434128, PubMed:20434986, PubMed:20501937, PubMed:21765415). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity).

Viewer

Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation AMBRA1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXA2 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BCL3 0.439
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation, binding CREBBP 0.533
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MTOR 0.523
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CHUK 0.684
Publications: 3 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ up-regulates activity img/direct-activation.png phosphorylation IKBKB 0.653
Publications: 2 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation COPS5 0.329
Publications: 2 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation NCOR2 0.426
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation ELAVL1 0.328
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKBIA 0.893
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation CYLD 0.524
Publications: 5 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CYLD 0.524
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TRAF4 0.392
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RELA 0.841
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MTURN 0.2
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation TAX1BP1 0.39
Publications: 2 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation FOXO 0.553
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXO3 0.553
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NCOA3 0.403
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NFKB2 0.784
Publications: 2 Organism: Mus Musculus
Pathways:NF-KB Non Canonical
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKB1 0.737
Publications: 7 Organism: Mus Musculus, Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHUK 0.389
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHUK 0.508
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHUK 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHUK 0.653
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CCND1 0.389
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MAP3K14 0.684
Publications: 1 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation CHUK 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding CHUK 0.416
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NfKb-p65/p50 0.789
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CHUK 0.573
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition CHUK 0.8
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation TSC2 0.301
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding IKK-complex 0.774
Publications: 1 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination CHUK 0.519
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IRF7 0.68
Publications: 1 Organism: Homo Sapiens