Version 5.4
Bos taurus Protein: CHUK
Summary
InnateDB Protein IDBP-690806.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CHUK
Protein Name Inhibitor of nuclear factor kappa-B kinase subunit alpha
Synonyms
Species Bos taurus
Ensembl Protein ENSBTAP00000009985
InnateDB Gene IDBG-638708 (CHUK)
Protein Structure
UniProt Annotation
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 (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus. {ECO:0000250}.
Disease Associations
Tissue Specificity
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.
They are also associated with 164 interaction(s) predicted by orthology.
Experimentally validated
Total 5 [view]
Protein-Protein 5 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 164 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008384 IkappaB kinase activity
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity
GO:0097110 scaffold protein binding
Biological Process
GO:0002011 morphogenesis of an epithelial sheet
GO:0006468 protein phosphorylation
GO:0007252 I-kappaB phosphorylation
GO:0007595 lactation
GO:0016310 phosphorylation
GO:0030316 osteoclast differentiation
GO:0033598 mammary gland epithelial cell proliferation
GO:0042475 odontogenesis of dentin-containing tooth
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0060749 mammary gland alveolus development
GO:0071356 cellular response to tumor necrosis factor
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0043231 intracellular membrane-bounded organelle
Protein Structure and Domains
PDB ID
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR022007 I-kappa-kinase-beta NEMO binding domain
IPR029071 Ubiquitin-related domain
PFAM PF00069
PF07714
PF12179
PRINTS PR00109
PIRSF
SMART SM00220
SM00219
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt Q95KV1
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 281073
UniGene Bt.63925
RefSeq NP_776446
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL AJ414555 BC134510
GenPept AAI34511 CAC93686

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca