CHUK
entrez
1147
canonical
uniprot
O15111
canonical
ensembl
ENSG00000213341
resolver
ensp
ENSP00000359424
resolver
ensp
ENSP00000669949
resolver
ensp
ENSP00000669952
resolver
enst
ENST00000370397
resolver
genesymbol
CHUK
resolver
genesymbol_syn
IKKA
resolver
genesymbol_syn
TCF16
resolver
hgnc
HGNC:1974
resolver
uniprot
O14666
resolver
uniprot
Q13132
resolver
uniprot
Q5W0I4
resolver
uniprot
Q92467
resolver
uniprot_entry
IKKA_HUMAN
resolver
uniprot_sec
O14666
resolver
uniprot_sec
Q13132
resolver
uniprot_sec
Q5W0I4
resolver
uniprot_sec
Q92467
resolver
activity_regulation
ACTIVITY REGULATION: Activated when phosphorylated and inactivated when dephosphorylated.
uniprot
proteins
amino_acid_sequence
MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCHEIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRCFVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHLSTIIHEANEEQGNSMMNLDWSWLTE
uniprot
proteins
disease_involvement
DISEASE: Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. {ECO:0000269|PubMed:20961246}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Bartsocas-Papas syndrome 2 (BPS2) [MIM:619339]: An autosomal recessive, severe form of popliteal pterygium syndrome. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but they are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. {ECO:0000269|PubMed:25691407}. Note=The disease may be caused by variants affecting the gene represented in this entry.
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 (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). 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 (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). 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:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). 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. 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 (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:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}.
uniprot
proteins
mass_dalton
84640
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="T->A: Loss of phosphorylation and decrease of kinase activity."; /evidence="ECO:0000269|PubMed:10485710"; MUTAGEN 44; /note="K->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9346484"; MUTAGEN 44; /note="K->M: Loss of autophosphorylation."; /evidence="ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9346484"; MUTAGEN 176; /note="S->A: Loss of phosphorylation and of activity."; /evidence="ECO:0000269|PubMed:9346484, ECO:0000269|PubMed:9520446"; MUTAGEN 176; /note="S->E: Full activation."; /evidence="ECO:0000269|PubMed:9346484, ECO:0000269|PubMed:9520446"; MUTAGEN 179; /note="T->A: No change in phosphorylation."; /evidence="ECO:0000269|PubMed:9520446"; MUTAGEN 180; /note="S->A: No change in phosphorylation."; /evidence="ECO:0000269|PubMed:9520446
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated.; PTM: Ubiquitinated by TRIM56 via 'Lys-63'-linked ubiquitination, promoting activation of CHUK/IKKA. {ECO:0000269|PubMed:35952808}.; PTM: (Microbial infection) Acetylation of Thr-179 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway. {ECO:0000269|PubMed:17116858}.
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
10485710
uniprot
proteins
pubmed
10712233
uniprot
proteins
pubmed
11971985
uniprot
proteins
pubmed
12612076
uniprot
proteins
pubmed
12789342
uniprot
proteins
pubmed
15084260
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15173580
uniprot
proteins
pubmed
15456791
uniprot
proteins
pubmed
16177806
uniprot
proteins
pubmed
17116858
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17434128
uniprot
proteins
pubmed
17540171
uniprot
proteins
pubmed
18462684
uniprot
proteins
pubmed
18626576
uniprot
proteins
pubmed
19088076
uniprot
proteins
pubmed
19150425
uniprot
proteins
pubmed
20434986
uniprot
proteins
pubmed
20501937
uniprot
proteins
pubmed
20855622
uniprot
proteins
pubmed
20961246
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21765415
uniprot
proteins
pubmed
23091055
uniprot
proteins
pubmed
23776175
uniprot
proteins
pubmed
25691407
uniprot
proteins
pubmed
26334375
uniprot
proteins
pubmed
27426725
uniprot
proteins
pubmed
30217973
uniprot
proteins
pubmed
30341167
uniprot
proteins
pubmed
32935379
uniprot
proteins
pubmed
35952808
uniprot
proteins
pubmed
8777433
uniprot
proteins
pubmed
9244310
uniprot
proteins
pubmed
9252186
uniprot
proteins
pubmed
9346484
uniprot
proteins
pubmed
9520446
uniprot
proteins
pubmed
9751059
uniprot
proteins
pubmed
9813230
uniprot
proteins
pubmed
9819420
uniprot
proteins
sequence_length
745
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:30341167}. Nucleus {ECO:0000269|PubMed:12789342}. Note=Shuttles between the cytoplasm and the nucleus.
uniprot
proteins