Q60680
uniprot
Q60680
canonical
activity_regulation
ACTIVITY REGULATION: Activated when phosphorylated and inactivated when dephosphorylated.
uniprot
proteins
amino_acid_sequence
MERPPGLRPGAGGPWEMRERLGTGGFGNVSLYQHRELDLKIAIKSCRLELSSKNRERWCHEIQIMKKLDHANVVKACDVPEELNFLINDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKTIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMTGEVRFSSHLPQPNSLCSLIVEPMESWLQLMLNWDPQQRGGPIDLTLKQPRCFALMDHILNLKIVHILNMTSAKIISFLLPCDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFRKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYSEVGVIGYLEDQIMSLHTEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPPDHLYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGTVTPPVSAWLPPTLADREHPLTCVVTPQDGETLAQMIEENLNCLGHLSTIIREANEDQSSSLMSLDWSWLAE
uniprot
proteins
ec_number
2.7.11.10
uniprot
proteins
function
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 a 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. Also participates 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 (PubMed:12789342). 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 (PubMed:30988283). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (By similarity). {ECO:0000250|UniProtKB:O15111, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:30988283}.
uniprot
proteins
mass_dalton
84729
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by TRIM56 via 'Lys-63'-linked ubiquitination, promoting activation of CHUK/IKKA. {ECO:0000250|UniProtKB:O15111}.; PTM: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated. {ECO:0000269|PubMed:9520401}.
uniprot
proteins
protein_family
I-kappa-B kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10195894
uniprot
proteins
pubmed
10195895
uniprot
proteins
pubmed
10712233
uniprot
proteins
pubmed
10733566
uniprot
proteins
pubmed
12789342
uniprot
proteins
pubmed
14585990
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18194271
uniprot
proteins
pubmed
20622870
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
30988283
uniprot
proteins
pubmed
7558004
uniprot
proteins
pubmed
8777433
uniprot
proteins
pubmed
9520401
uniprot
proteins
pubmed
9819420
uniprot
proteins
sequence_length
745
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12789342}. Nucleus {ECO:0000269|PubMed:12789342}. Note=Shuttles between the cytoplasm and the nucleus.
uniprot
proteins