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FLASH GENE
Symbol CHUK contributors: mct - updated : 09-11-2014
HGNC name conserved helix-loop-helix ubiquitous kinase
HGNC id 1974
Corresponding disease
COCS Cocoon syndrome
Location 10q24.31      Physical location : 101.948.124 - 101.989.344
Synonym name
  • I-kappa-B kinase-alpha
  • inhibitor of kappa light polypeptide gene enhancer in B cells, kinase, alpha, subunit
  • nuclear factor NF-kappa-B inhibitor kinase alpha
  • Synonym symbol(s) IKBKA, IKKA, IKK1, NFKBIKA, TCF16, IKK-alpha
    EC.number 2.7.11.10
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 41.22 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    text structure
  • a binding site for the ETS-1 protein (product of the ETS-1 proto-oncogene) which is negatively regulated by binding of TP53 on the protein
  • proximal 5'-flanking region contains a functional promoter reciprocally regulated by TP53 and ETS1
  • MAPPING cloned Y linked N status provisional
    Physical map
    CNNM1 10q24.33 cyclin M1 GOT1 10q24 glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1) NKX2-3 10q24.33 NK2 transcription factor related, locus 3 (Drosophila) SLC25A28 10q24 solute carrier family 25, member 28 LALP1 10q23-q24 solute carrier family 25, member 28 COX15 10q24 COX15 homolog, cytochrome c oxidase assembly protein (yeast) CGI-32 10q24.31 CGI-32 protein ABCC2 10q24 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 KIAA1010 10q25.1 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 CPN1 10q24.31 carboxypeptidase N, polypeptide 1, 50kD KEO4 CHUK 10q24-q25 conserved helix-loop-helix ubiquitous kinase FLJ10998 10q24.31 hypothetical protein FLJ10998 MGC10120 10q24.31 hypothetical protein MGC10120 PKD2L1 10q24-q25 polycystic kidney disease 2-like 1 SCD 10q23-q24 stearoyl-CoA desaturase (delta-9-desaturase) LOC90271 10q24.31 hypothetical protein LOC90271 WNT8B 10q24 wingless-type MMTV integration site family, member 8B SEC31L2 10q24.32 SEC31-like 2 (S. cerevisiae) NDUFB8 10q23.2-q23.33 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa HIF1AN 10q24 hypoxia-inducible factor 1, alpha subunit inhibitor PAX2 10q22.1-q24.3 paired box gene 2 C10orf6 10q24.31 chromosome 10 open reading frame 6 SEMA4G 10q24.2 sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G MRPL43 10q24.1-q24.3 mitochondrial ribosomal protein L43 PEO1 KIAA1813 10q24 KIAA1813 protein FLJ23209 10q24.32 hypothetical protein FLJ23209
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3539 - 745 - 2006 17102620
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Lymphoid/Immunelymph node   highly
    Urinarykidney   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines cervical carcinoma
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • serine/threonine kinase domain
  • a leucine zipper domain
  • a conserved region in the C-terminal tail, (NEMO-binding domain, NBD) important for interaction with IKBKG (Lo 2008)
  • conjugated PhosphoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Chuk
    Homologene
    FAMILY Ser/Thr family of protein kinases
    CATEGORY enzyme , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • deactivating the inhibitor of kappa light polypeptide enhancer in B cells (NFKB)
  • phosphorylating sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor
  • is an essential regulator of NFKB-dependent gene expression through control of promoter-associated histone phosphorylation after cytokine exposure
  • involved in the negative regulation of macrophage activation and inflammation
  • promoting recombinase activator genes (RAG) transcription
  • playing a major role in regulating the biological effects of estrogen via its promoter association
  • controlling skeletal and craniofacial morphogenesis by repressing expression of fibroblast growth factor (FGF) family members, such as FGF8
  • having an important role in the activation of nuclear factor-kB (NF-kB), a key regulator of normal and tumor cell proliferation, apoptosis, and response to chemotherapy
  • playing a potential role in bile duct disease
  • functioning as a molecular switch that controls epidermal differentiation
  • functions as a tumor suppressor in human squamous cell carcinomas (SCCs) of skin, lungs, and head and neck
  • CHUK and alkaline phosphatase are negative regulators of IRF5 activity in MYD88 pathway and have role in the control of the inflammatory response by attenuation of IRF5 activity
  • plays a critical role in mediation of the UVB-induced G0/G1 cell cycle arrest response by suppressing Cyclin D1 expression
  • role of IKKalpha in regulating cell cycle progression during the cellular UVB response
  • key mediator of the inflammation and metastasis in prostate cancer, playing a major role in prostate cancer invasion and metastasis, but not in cell proliferation
  • RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth 8)
  • IKBKG together with the catalytic subunits CHUK and IKBKB, plays an essential role in the formation of the IKK complex and in the activation of the canonical NFKB pathway
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development , immunity/defense
    text
  • immune response
  • embryogenesis, morphogenesis
  • PATHWAY
    metabolism
    signaling
    a component
  • preferentially complexing with IKBKB, but also forming homodimer
  • component of a cytokine-activated protein complex (NCOA2, NCOA3, IKKB, IKBKG and CREBBP)
  • IKBKG together with catalytic subunits CHUK and IKBKB, forms the IKB kinase (IKK) complex, a key regulator of NFKB pathway signaling
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    ATP binding
    protein
  • interacting with MEKK1, NEMO, TRPC4AP, NALP2, MAVS/IPS1
  • interacting with CREBP
  • regulating the M phase of the cell cycle by modulating Aurora A phosphorylation
  • cooperating with IKBKB for regulating liver immune homeostasis and bile duct integrity (share a redundant function in mediating canonical NFKB signaling in hepatocytes and protecting the liver from TNF toxicity)
  • CHUK and alternative NFKB regulate PPARGC1B to promote oxidative muscle metabolism
  • NFKB1 signaling pathway, which involves both NFKBIA and CHUK, plays an important role in platelet CD40 signaling, activation and aggregation in response to sCD40LG
  • UBE2N-CHUK signaling axis regulates the molecular program that maintains Treg cell function and prevents Treg cells from acquiring inflammatory phenotypes
  • IKBKG is essential for IKBKB activation by inflammatory stimuli, and also a specificity factor that directs IKBKB activity toward CHUK
  • CHUK and IKBKB physically interacted with RICTOR
  • CHUK and IKBKB are RELB interacting partners whose activation by TNF promotes RELB phosphorylation at serine 472
  • cell & other
    REGULATION
    activated by phosphorylation
    Other phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A
    autophosphorylated
    ASSOCIATED DISORDERS
    corresponding disease(s) COCS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    protecting against neurodegeneration in cerebral ischemia
    constitutional       loss of function
    in exon 15
    tumoral     --low  
    provides a selective growth advantage that cooperates with Ras activity to promote skin carcinogenesis
    Susceptibility to squamous cell carcinomas
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting CHUK might be promising for the prevention of UVB-induced cell damage and tumorigenic effects
    miscelleaneous  
    CHUK inhibitor for stroke therapy
    cancer  
    loss of TP53-mediated control over ETS1-dependent transactivation of CHUK may represent a novel pathway for the constitutive activation of NF-kB-mediated gene expression and therapy resistance in cancer
    cancerreproductiveprostate
    silencing of CHUK with siRNA may therefore provide a promising therapeutic strategy for prostate cancer patients
    cancerdigestiveliver
    IKK-targeted gene therapy can be used in the treatment of hepatocellular carcinoma, a cancer that is notoriously resistant to radiation and chemotherapy
    ANIMAL & CELL MODELS
  • Ikkalpha(-/-) mice present with a hyperproliferative and undifferentiated epidermis characterized by complete absence of a granular layer and stratum corneum (Descarques, 2008)