Homo sapiens Gene: CHUK
Summary
InnateDB Gene IDBG-243385.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CHUK
Gene Name conserved helix-loop-helix ubiquitous kinase
Synonyms IKBKA; IKK-alpha; IKK1; IKKA; NFKBIKA; TCF16
Species Homo sapiens
Ensembl Gene ENSG00000213341
Encoded Proteins
conserved helix-loop-helix ubiquitous kinase
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
CHUK is part of the inhibitor kappaB kinase (IKK) complex that phosphorylates IRS1 at Ser(312) and this contributes to the insulin resistance mediated by activation of inflammatory pathways.
CHUK (IKK-alpha) is part of the IKK signalosome that phosphorylates NFKBIA and NFKBIB, leading to activation of NF-kappaB.
CHUK (IKKalpha) phosphorylates CREBBP (CBP), regulating the CBP-mediated crosstalk between NF-kappaB and p53, a critical factor in the promotion of cell proliferation and tumor growth.
CHUK is a unique molecule involved in TLR7/9-MyD88-dependent type I IFN production through dendritic cell subset-specific mechanisms.
CHUK has a key role in the negative feedback of NF-kB canonical signalling by orchestrating the assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation in response to proinflammatory stimuli such as TNF and IL1. (Demonstrated in mouse)
CHUK is required in dendritic cells to prime adaptive immunity to Listeria monocytogenes.
GNB2L1 (RACK1) negatively regulates NFκB activation by interacting with CHUK and IKBKB. The interaction interferes with the recruitment of the IKK complex to TRAF2 .
DDX3X initiates a multifaceted cellular program involving dynamic associations with hepatitis C virus (HCV) RNA and proteins, CHUK, stress granules, and lipid droplet surfaces for its crucial role in the HCV life cycle.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Chuk has a key role in the negative feedback of NF-kB canonical signalling by orchestrating the assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation in response to proinflammatory stimuli such as Tnf and Il1.
[Mus musculus] Epithelial cell-intrinsic Chuk expression and Tslp regulate group 3 innate lymphoid cell responses required to maintain intestinal barrier immunity.
Entrez Gene
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 10:100188298-100229619
Strand Reverse strand
Band q24.31
Transcripts
ENST00000370397 ENSP00000359424
ENST00000590930
ENST00000588656
ENST00000585551
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
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Not yet available
Pathways
NETPATH
TGF_beta_Receptor pathway
TNFalpha pathway
TCR pathway
BCR pathway
IL1 pathway
IL4 pathway
RANKL pathway
Leptin pathway
TWEAK pathway
IL11 pathway
REACTOME
AKT phosphorylates targets in the cytosol pathway
PIP3 activates AKT signaling pathway
DAP12 signaling pathway
DAP12 interactions pathway
RIP-mediated NFkB activation via ZBP1 pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
TRAF6 mediated NF-kB activation pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
IKK complex recruitment mediated by RIP1 pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
MyD88-independent cascade pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
IRAK1 recruits IKK complex pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
MyD88 cascade initiated on plasma membrane pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
NOD1/2 Signaling Pathway pathway
Downstream TCR signaling pathway
Interleukin-1 signaling pathway
Activation of NF-kappaB in B cells pathway
PI3K/AKT activation pathway
GAB1 signalosome pathway
Signaling by EGFR pathway
PI3K events in ERBB4 signaling pathway
Signaling by ERBB4 pathway
PI3K events in ERBB2 signaling pathway
Signaling by ERBB2 pathway
PI-3K cascade pathway
Signaling by FGFR pathway
Signaling by SCF-KIT pathway
Downstream signal transduction pathway
Signaling by PDGF pathway
Constitutive PI3K/AKT Signaling in Cancer pathway
Signaling by FGFR in disease pathway
FCERI mediated NF-kB activation pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Signaling by EGFR in Cancer pathway
Downstream signaling of activated FGFR pathway
TCR signaling pathway
Role of LAT2/NTAL/LAB on calcium mobilization pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Fc epsilon receptor (FCERI) signaling pathway
Signal Transduction pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Adaptive Immune System pathway
Immune System pathway
Signaling by Interleukins pathway
NGF signalling via TRKA from the plasma membrane pathway
Activated TLR4 signalling pathway
PI3K/AKT Signaling in Cancer pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
Signaling by the B Cell Receptor (BCR) pathway
Downstream signaling events of B Cell Receptor (BCR) pathway
Disease pathway
KEGG
Acute myeloid leukemia pathway
Epithelial cell signaling in Helicobacter pylori infection pathway
Apoptosis pathway
MAPK signaling pathway pathway
Small cell lung cancer pathway
B cell receptor signaling pathway pathway
Prostate cancer pathway
T cell receptor signaling pathway pathway
Toll-like receptor signaling pathway pathway
Chronic myeloid leukemia pathway
Adipocytokine signaling pathway pathway
Pancreatic cancer pathway
Chemokine signaling pathway pathway
Pathways in cancer pathway
RIG-I-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Chagas disease (American trypanosomiasis) pathway
Osteoclast differentiation pathway
Shigellosis pathway
Toxoplasmosis pathway
Hepatitis C pathway
INOH
CD4 T cell receptor signaling pathway
IL-7 signaling pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
JAK STAT pathway and regulation pathway
B cell receptor signaling pathway
EPO signaling pathway pathway
VEGF signaling pathway pathway
TNFR1 signaling pathway pathway
PID NCI
TCR signaling in naïve CD8+ T cells
Class I PI3K signaling events mediated by Akt
Validated nuclear estrogen receptor alpha network
TCR signaling in naïve CD4+ T cells
IL1-mediated signaling events
TNF receptor signaling pathway
TRAIL signaling pathway
FoxO family signaling
p75(NTR)-mediated signaling
BCR signaling pathway
Canonical NF-kappaB pathway
Validated transcriptional targets of TAp63 isoforms
Fc-epsilon receptor I signaling in mast cells
Alternative NF-kappaB pathway
Endogenous TLR signaling
HIV-1 Nef: Negative effector of Fas and TNF-alpha
Osteopontin-mediated events
FAS (CD95) signaling pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.594380
RefSeq NM_001278
HUGO
OMIM
CCDS CCDS7488
HPRD 02811
IMGT
EMBL
GenPept
RNA Seq Atlas