TARGETID

T65879

FORMERID

TTDR00255

UNIPROID

IKKA_HUMAN

TARGNAME

Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)

GENENAME

CHUK

TARGTYPE

Literature-reported target

SYNONYMS

Transcription factor 16; TCF16; TCF-16; Nuclear factor NFkappaB inhibitor kinase alpha; Nuclear factor NF-kappa-B inhibitor kinase alpha; NFKBIKA; Inhibitory kappa B kinasea; Inhibitor of nuclear factor kappa-B kinase subunit alpha; IkappaB kinase A; IkBKA; IKK1; IKK-alpha; IKK-A; I-kappa-B kinase alpha; I-kappa-B kinase 1; I kappa-B kinase alpha; Conserved helix-loop-helix ubiquitous kinase

FUNCTION

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. 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.

PDBSTRUC

5TQY; 5TQX; 5TQW; 5EBZ; 3BRT

BIOCLASS

Kinase

ECNUMBER

EC 2.7.11.10

SEQUENCE

MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCHEIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRCFVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHLSTIIHEANEEQGNSMMNLDWSWLTE

DRUGINFO

IKI-1

WIKIPATH

WP2526:PDGF Pathway

REACPATH

R-HSA-1169091:Activation of NF-kappaB in B cells

REACPATH

R-HSA-168638:NOD1/2 Signaling Pathway

REACPATH

R-HSA-1810476:RIP-mediated NFkB activation via ZBP1

REACPATH

R-HSA-198323:AKT phosphorylates targets in the cytosol

REACPATH

R-HSA-2871837:FCERI mediated NF-kB activation

REACPATH

R-HSA-445989:TAK1 activates NFkB by phosphorylation and activation of IKKs complex