Rabbit anti-Human CHUK/IKBKB Polyclonal Antibody

Uniprot Id

O15111

Target Species

Human

Target Name

CHUK

Target Full Name

Inhibitor of nuclear factor kappa-B kinase subunit alpha

Target 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. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity.

Target Involvement

Cocoon syndrome (COCOS)

Target Subcellular Location

Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus.

Target Protein Families

Protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily

Target Tissue Specificity

Widely expressed.

Target Synonyms

chuk; CHUK1; Conserved Helix Loop Helix Ubiquitous Kinase; Conserved helix loop ubiquitous kinase; Conserved helix-loop-helix ubiquitous kinase; I Kappa B Kinase 1; I Kappa B Kinase Alpha; I-kappa-B kinase 1; I-kappa-B kinase alpha; IkappaB kinase; IkB kinase alpha subunit; IkBKA; IKK 1; IKK A; IKK a kinase; IKK-A; IKK-alpha; IKK1; IKKA; IKKA_HUMAN; Inhibitor Of Kappa Light Polypeptide Gene Enhancer In B Cells; Inhibitor Of Nuclear Factor Kappa B Kinase Alpha Subunit; Inhibitor of nuclear factor kappa-B kinase subunit alpha; NFKBIKA; Nuclear Factor Kappa B Inhibitor Kinase Alpha; Nuclear factor NF kappa B inhibitor kinase alpha; Nuclear factor NF-kappa-B inhibitor kinase alpha; Nuclear factor NFkappaB inhibitor kinase alpha; Nuclear Factor Of Kappa Light Chain Gene Enhancer In B Cells Inhibitor; TCF-16; TCF16; Transcription factor 16

Target Background

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor.