Names & Taxonomy
- Uniprot ID:
- O15111
- Entry Name:
- IKKA_HUMAN
- Status:
- reviewed
- Protein Names:
- Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (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)
- Gene Names:
- CHUK IKKA TCF16
- Gene Names Primary:
- CHUK
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 745
- Sequence:
- MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCHEIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRCFVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHLSTIIHEANEEQGNSMMNLDWSWLTE
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
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 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:15084260).
- Catalytic Activity:
- ATP + = ADP + .
- Enzyme Regulation:
- ENZYME REGULATION: Activated when phosphorylated and inactivated when dephosphorylated.
- Active Site:
- ACT_SITE 144 144 Proton acceptor.
- Cross Reference Drug Bank:
- DB06151 DB00233 DB00244 DB00795
- Gene Ontology Go:
- CD40 receptor complex
cytoplasm
cytoplasmic side of plasma membrane
cytosol
IkappaB kinase complex
intracellular membrane-bounded organelle
nucleoplasm
ATP binding
identical protein binding
IkappaB kinase activity
protein heterodimerization activity
protein homodimerization activity
protein kinase activity
scaffold protein binding
anatomical structure morphogenesis
cell surface receptor signaling pathway
cellular response to tumor necrosis factor
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
immune response
inflammatory response
innate immune response
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
NIK/NF-kappaB signaling
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
nucleotide-binding oligomerization domain containing signaling pathway
phosphatidylinositol-mediated signaling
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
protein phosphorylation
regulation of tumor necrosis factor-mediated signaling pathway
response to acetate
response to amino acid
response to drug
response to hydroperoxide
response to lipopolysaccharide
response to toxic substance
response to virus
Rho protein signal transduction
skeletal muscle contraction
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
striated muscle cell differentiation
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
tumor necrosis factor-mediated signaling pathway - Gene Ontology Biological Process:
- anatomical structure morphogenesis
cell surface receptor signaling pathway
cellular response to tumor necrosis factor
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
immune response
inflammatory response
innate immune response
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
neurotrophin TRK receptor signaling pathway
NIK/NF-kappaB signaling
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
nucleotide-binding oligomerization domain containing signaling pathway
phosphatidylinositol-mediated signaling
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
protein phosphorylation
regulation of tumor necrosis factor-mediated signaling pathway
response to acetate
response to amino acid
response to drug
response to hydroperoxide
response to lipopolysaccharide
response to toxic substance
response to virus
Rho protein signal transduction
skeletal muscle contraction
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
striated muscle cell differentiation
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
tumor necrosis factor-mediated signaling pathway - Gene Ontology Molecular Function:
- ATP binding
identical protein binding
IkappaB kinase activity
protein heterodimerization activity
protein homodimerization activity
protein kinase activity
scaffold protein binding - Gene Ontology Cellular Component:
- CD40 receptor complex
cytoplasm
cytoplasmic side of plasma membrane
cytosol
IkappaB kinase complex
intracellular membrane-bounded organelle
nucleoplasm - Keywords:
- 3D-structure
ATP-binding
Acetylation
Complete proteome
Cytoplasm
Direct protein sequencing
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase - Interacts With:
- Q6TY28; Q6TY35; Q8B5B5; P32121; Q16543; P46527; P03129; Q07857; Q80901; Q13451; P07900; O14920; Q9Y6K9; Q92985; Q99558; P01106; P25963; Q77M19; Q04206; Q86VP1; P24772