InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CHUK

Summary

InnateDB Protein

IDBP-86266.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CHUK

Protein Name

conserved helix-loop-helix ubiquitous kinase

Synonyms

IKBKA; IKK-alpha; IKK1; IKKA; NFKBIKA; TCF16;

Species

Homo sapiens

Ensembl Protein

ENSP00000359424

InnateDB Gene

IDBG-243385 (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. {ECO:0000269PubMed:12789342, ECO:0000269PubMed:17434128, ECO:0000269PubMed:20434986, ECO:0000269PubMed:20501937, ECO:0000269PubMed:21765415}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12789342}. Nucleus {ECO:0000269PubMed:12789342}. Note=Shuttles between the cytoplasm and the nucleus.

Disease Associations

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:0000269PubMed:20961246}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 267 experimentally validated interaction(s) in this database.
They are also associated with 25 interaction(s) predicted by orthology.

Experimentally validated
Total	267 [view]
Protein-Protein	253 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	3 [view]
DNA-RNA	0

Predicted by orthology
Total	25 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008384	IkappaB kinase 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:0001101	response to acid
GO:0002011	morphogenesis of an epithelial sheet
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0003009	skeletal muscle contraction
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0006955	immune response
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007252	I-kappaB phosphorylation
GO:0007266	Rho protein signal transduction
GO:0007595	lactation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009615	response to virus
GO:0009636	response to toxic substance
GO:0009653	anatomical structure morphogenesis
GO:0010033	response to organic substance
GO:0030316	osteoclast differentiation
GO:0032481	positive regulation of type I interferon production
GO:0032496	response to lipopolysaccharide
GO:0033194	response to hydroperoxide
GO:0033598	mammary gland epithelial cell proliferation
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042493	response to drug
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043200	response to amino acid
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050852	T cell receptor signaling pathway
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051146	striated muscle cell differentiation
GO:0060749	mammary gland alveolus development
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0071356	cellular response to tumor necrosis factor

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0008385	IkappaB kinase complex
GO:0009898	cytoplasmic side of plasma membrane
GO:0035631	CD40 receptor complex
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