CHUK (component of inhibitor of nuclear factor kappa B kinase complex)

Gene

• Entrez ID: 1147
• Gene name: Component of inhibitor of nuclear factor kappa B kinase complex
• Gene symbol: CHUK
• Synonyms: BPS2, IKBKA, IKK-alpha, IKK1, IKKA, NFKBIKA, TCF16
• Chromosome: 10
• Chromosome location: 10q24.31
• Summary: 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. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs267606736	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005552	hsa-miR-15a-5p	Luciferase reporter assay, qRT-PCR, Western blot	20711193
MIRT005554	hsa-miR-16-5p	Luciferase reporter assay, qRT-PCR, Western blot	20711193
MIRT005555	hsa-miR-223-3p	Luciferase reporter assay, qRT-PCR, Western blot	20711193
MIRT007041	hsa-miR-23b-3p	Luciferase reporter assay	22660635
MIRT007169	hsa-miR-195-5p	Luciferase reporter assay	23487264
MIRT732536	hsa-miR-98-5p	Luciferase reporter assay	25623956
MIRT734834	hsa-miR-23a-3p	Luciferase reporter assay	27537390

Transcription factors

Transcription factor	Regulation	Reference
ETS1	Activation	15469934
TP53	Repression	15469934

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	TAS
GO:0003009	Process	Skeletal muscle contraction	IEA
GO:0004672	Function	Protein kinase activity	IDA	20434986
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	8246997, 9520446, 9751060, 10521409, 10733566, 11297557, 11971985, 12482991, 12486103, 12730857, 14743216, 15125834, 15601829, 15749833, 16126728, 16129692, 16286467, 16319058, 16498412, 16938294, 17363973, 17568778, 17620599, 18266467, 18268325, 18579519, 18922877, 19666608, 198753
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	30341167
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IDA	20434986
GO:0006954	Process	Inflammatory response	TAS	18626576
GO:0006955	Process	Immune response	TAS	9346484
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IMP	26514923
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS	18626576
GO:0007252	Process	I-kappaB phosphorylation	TAS	9252186
GO:0007266	Process	Rho protein signal transduction	IEA
GO:0008384	Function	IkappaB kinase activity	IBA	21873635
GO:0008384	Function	IkappaB kinase activity	TAS	18626576
GO:0008385	Component	IkappaB kinase complex	IBA	21873635
GO:0008385	Component	IkappaB kinase complex	TAS	18626576
GO:0009615	Process	Response to virus	TAS	18626576
GO:0009636	Process	Response to toxic substance	IEA
GO:0009653	Process	Anatomical structure morphogenesis	TAS	10747982
GO:0009898	Component	Cytoplasmic side of plasma membrane	ISS
GO:0010034	Process	Response to acetate	IEA
GO:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	TAS
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IMP	11536016
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032727	Process	Positive regulation of interferon-alpha production	IMP	24784232
GO:0033194	Process	Response to hydroperoxide	IEA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA	21873635
GO:0034614	Process	Cellular response to reactive oxygen species	IMP	26514923
GO:0035631	Component	CD40 receptor complex	ISS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0038061	Process	NIK/NF-kappaB signaling	IMP	26514923
GO:0038061	Process	NIK/NF-kappaB signaling	TAS
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042493	Process	Response to drug	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	23091055
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	23487264
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	TAS
GO:0043200	Process	Response to amino acid	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045087	Process	Innate immune response	TAS	18626576
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	26514923
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	23091055
GO:0046982	Function	Protein heterodimerization activity	IDA	23091055
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS	18626576
GO:0051146	Process	Striated muscle cell differentiation	IEA
GO:0051403	Process	Stress-activated MAPK cascade	TAS
GO:0061847	Process	Response to cholecystokinin	IEA
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0071276	Process	Cellular response to cadmium ion	IMP	26514923
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	23091055
GO:0097110	Function	Scaffold protein binding	IDA	23776175
GO:0098586	Process	Cellular response to virus	IMP	24784232
GO:1990459	Function	Transferrin receptor binding	IPI	23016877

Other IDs

• MIM: 600664
• HGNC: 1974
• e!Ensembl: ENSG00000213341

Protein

• UniProt ID: O15111
• Protein name: 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)
• Protein 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:12789342, PubMed:15084260, PubMed:17434128, PubMed:20434986, PubMed:20501937, PubMed:21765415). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity).
• PDB: 3BRT, 5EBZ, 5TQW, 5TQX, 5TQY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	15 → 298	Protein kinase domain	Domain
  PF18397	IKBKB_SDD	386 → 659	IQBAL scaffold dimerization domain	Domain
  PF12179	IKKbetaNEMObind	707 → 743	I-kappa-kinase-beta NEMO binding domain	Domain

• Sequence:

  MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCH
  EIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQ
  ILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTS
  FVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPK
  CIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRC
  FVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGI
  SLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPI
  IQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKL
  EFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAE
  IMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRV
  LKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQ
  SSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHL
  STIIHEANEEQGNSMMNLDWSWLTE

• Sequence length: 745