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CHUK Gene

protein-coding   GIFtS: 70
GCID: GC10M101938

Conserved Helix-Loop-Helix Ubiquitous Kinase


(Previous symbol: TCF16)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Conserved Helix-Loop-Helix Ubiquitous Kinase1 2 3     I-Kappa-B Kinase-Alpha2
TCF161 2 3     IkB Kinase Alpha Subunit2
IKK12 3 5     IKK-A Kinase2
IKKA2 3 5     Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Alpha2
NFKBIKA2 3 5     Nuclear Factor NFkappaB Inhibitor Kinase Alpha2
Transcription Factor 162 3     IKK-A3
IKK-alpha2 3     IkBKA3
TCF-162 3     I-Kappa-B Kinase Alpha3
I-Kappa-B Kinase 12 3     IkappaB Kinase3
EC 2.7.11.103 8     Nuclear Factor NF-Kappa-B Inhibitor Kinase Alpha3
IKBKA2 5     EC 2.7.118

External Ids:    HGNC: 19741   Entrez Gene: 11472   Ensembl: ENSG000002133417   OMIM: 6006645   UniProtKB: O151113   

Export aliases for CHUK gene to outside databases

Previous GC identifers: GC10M100841 GC10M101181 GC10M102079 GC10M101612 GC10M095577


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CHUK Gene:
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)

GeneCards Summary for CHUK Gene:
CHUK (conserved helix-loop-helix ubiquitous kinase) is a protein-coding gene. Diseases associated with CHUK include cocoon syndrome, and skin papilloma. GO annotations related to this gene include protein heterodimerization activity and protein homodimerization activity. An important paralog of this gene is IKBKB.

UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111
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

summary for CHUK Gene:
IkappaB Kinase (IKK) is an enzyme complex that forms part of the NF-kappaB signaling pathway. The complex is
comprised of three subunits (IKKalpha (IKK1), IKKbeta (IKK2) and IKKgamma (NEMO)), the alpha- and
beta-subunits are catalytically active whereas the gamma-subunit serves a regulatory function. Activation of
NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB
kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation
also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus
and regulate gene expression.

Gene Wiki entry for CHUK Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000010.11  NT_030059.14  NC_018921.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CHUK gene promoter:
         Pax-5   FOXO3   POU6F1 (c2)   LCR-F1   FOXO3b   RORalpha1   PPAR-gamma1   c-Myb   FOXO3a   PPAR-gamma2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCHUK promoter sequence
   Search Chromatin IP Primers for CHUK

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CHUK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q24-q25   Ensembl cytogenetic band:  10q24.31   HGNC cytogenetic band: 10q24-q25

CHUK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CHUK gene location

GeneLoc information about chromosome 10         GeneLoc Exon Structure

GeneLoc location for GC10M101938:  view genomic region     (about GC identifiers)

Start:
101,948,055 bp from pter      End:
101,989,376 bp from pter
Size:
41,322 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111 (See protein sequence)
Recommended Name: Inhibitor of nuclear factor kappa-B kinase subunit alpha  
Size: 745 amino acids; 84640 Da
Subunit: Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four
alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to
associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates
with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of
NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA,
IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Directly interacts with IKK-gamma/NEMO and TRPC4AP (By similarity). May
interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2. Interacts
with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces
PIAS1 phosphorylation. Interacts with ZNF268 isoform 2; the interaction is further increased in a
TNF-alpha-dependent manner
1 PDB 3D structure from and Proteopedia for CHUK:
3BRT (3D)    
Secondary accessions: O14666 Q13132 Q5W0I4 Q92467

Explore the universe of human proteins at neXtProt for CHUK: NX_O15111

Explore proteomics data for CHUK at MOPED

Post-translational modifications: 

  • Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A.
    Autophosphorylated1
  • Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B
    signaling pathway1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for CHUK (O15111) (see all 23)
     QGQRAAM  RDLKPEN  QQLKAKL  NYIVQDSK 


    See CHUK Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_001269.3  
    ENSEMBL proteins: 
     ENSP00000359424  
    Reactome Protein details: O15111

    CHUK Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant CHUK Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for CHUK
    OriGene Custom MassSpec
    OriGene Custom Protein Services for CHUK
    GenScript Custom Purified and Recombinant Proteins Services for CHUK
    Novus Biologicals CHUK Proteins
    Novus Biologicals CHUK Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for CHUK

    CHUK Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of CHUK
    R&D Systems Antibodies for CHUK (IKK alpha)
    Cell Signaling Technology (CST) Antibodies for CHUK  (IKKA)
    OriGene Antibodies for CHUK
    OriGene Custom Antibody Services for CHUK
    Novus Biologicals CHUK Antibodies
    Abcam antibodies for CHUK (O14920, O15111)
    Cloud-Clone Corp. Antibodies for CHUK
    ThermoFisher Antibody for CHUK
    LSBio Antibodies in human, mouse, rat for CHUK

    CHUK Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for CHUK
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for CHUK
    Cell Signaling Technology (CST) Sandwich ELISA Kits for CHUK (IKKA)
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for CHUK
    Cloud-Clone Corp. CLIAs for CHUK


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: conserved helix-loop-helix ubiquitous kinase
    IKK family

    Selected InterPro protein domains (see all 6):
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry O15111

    ProtoNet protein and cluster: O15111

    UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111
    Domain: The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and
    hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with
    NEMO/IKBKG
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily
    Similarity: Contains 1 protein kinase domain


    CHUK for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: IKKA_HUMAN, O15111
    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
    Catalytic activity: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]
    Enzyme regulation: Activated when phosphorylated and inactivated when dephosphorylated

         Genatlas biochemistry entry for CHUK:
    I kappa B alpha-kinase inhibitor of kappa light polypeptide enhancer in B cells (NFKB),kinase alpha,activated by
    MEKK1,complexing with IKBKB

         Enzyme Numbers (IUBMB): EC 2.7.11.101 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity IDA--
    GO:0004713protein tyrosine kinase activity ----
    GO:0005515protein binding IPI10521409
    GO:0005524ATP binding IEA--
    GO:0008384IkappaB kinase activity TAS18626576
         
    CHUK for ontologies           About GeneDecksing


    Phenotypes:
         4 GenomeRNAi human phenotypes for CHUK:
     Decreased influenza A/WSN/33 r  Decreased substrate adherent c  Downregulation of NF-kappaB pa  Downregulation of NF-kappaB pa 

         Selected MGI mutant phenotypes (inferred from 9 alleles(MGI details for Chuk) (see all 22):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  liver/biliary system  mortality/aging 

    CHUK for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for CHUK: Chuktm1Ver Chuktm1.1Mpa Chuktm1Aki

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CHUK
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CHUK

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CHUK
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CHUK

    miRNA
    Products:
        
    miRTarBase miRNAs that target CHUK:
    hsa-mir-16-5p (MIRT005554), hsa-mir-223-3p (MIRT005555), hsa-mir-15a-5p (MIRT005552), hsa-mir-195-5p (MIRT007169), hsa-mir-23b-3p (MIRT007041)

    Block miRNA regulation of human, mouse, rat CHUK using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CHUK (see all 35):
    hsa-miR-323-3p hsa-miR-607 hsa-let-7d hsa-miR-374c hsa-miR-223 hsa-let-7g hsa-let-7a hsa-miR-520g
    SwitchGear 3'UTR luciferase reporter plasmidCHUK 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for CHUK
    Predesigned siRNA for gene silencing in human, mouse, rat CHUK

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for CHUK

    Clone
    Products:
         
    OriGene clones in human, mouse for CHUK (see all 10)
    OriGene ORF clones in mouse, rat for CHUK
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: CHUK (NM_001278)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CHUK
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CHUK

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for CHUK
    Browse ESI BIO Cell Lines and PureStem Progenitors for CHUK 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CHUK


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    IKKA_HUMAN, O15111: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    nucleus5
    plasma membrane3
    endoplasmic reticulum1
    extracellular1
    golgi apparatus1
    lysosome1
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0008385IkappaB kinase complex TAS18626576

    CHUK for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CHUK About   (see all 117)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1TWEAK Pathway
    TWEAK Pathway0.87
    HIV-1 Nef- Negative effector of Fas and TNF-alpha0.46
    DR3 Signaling0.87
    Apoptotic Pathways Triggered By HIV10.42
    TNFR1 Pathway0.56
    Apoptosis through Death Receptors0.42
    TNF Signaling0.55
    TRAIL Pathway0.40
    2NOD-like Receptor Signaling Pathways
    Toll-Like receptor Signaling Pathways0.58
    Mucin expression in CF via TLRs, EGFR signaling pathways0.42
    NOD-like Receptor Signaling Pathways0.58
    Immune response IL 1 signaling pathway0.42
    Inflammasome Activation Pathways0.51
    Pathogen or Damage-activated C-Type Lectin Receptor Signaling Pathways0.31
    IL-1 Family Signaling Pathways0.44
    3RANK Signaling in Osteoclasts
    BAFF in B-Cell Signaling0.92
    Apoptosis and survival APRIL and BAFF signaling0.39
    APRIL Pathway0.92
    RANK Pathway0.38
    RANK Signaling in Osteoclasts0.45
    RANKL/RANK Signaling Pathway0.31
    4Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways0.68
    NOD-like receptor signaling pathway0.37
    NOD1/2 Signaling Pathway0.68
    NOD pathway0.33
    5Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Development IGF 1 receptor signaling0.48
    Signal transduction AKT signaling0.49
    Immune response IL 4 signaling pathway0.39

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for CHUK (see all 7)
        NOD-like Receptor Signaling Pathways
    Inflammasome Activation Pathways
    IL-1 Family Signaling Pathways
    IL-17 Family Signaling Pathways
    Toll-Like receptor Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CHUK (see all 72)
        Toll-Like Receptors Pathway
    JNK Pathway
    NF-kappaB Activation by Viruses
    RANK Pathway
    RANK Signaling in Osteoclasts

    1 Cell Signaling Technology (CST) Pathway for CHUK
        NF-kappaB Signaling

    5 Tocris Bioscience Pathways for CHUK
        Akt Pathway
    Insulin Pathway
    Apoptosis Pathway
    Toll-like Receptor Pathway
    NF-kappaB Pathway

    Selected GeneGo (Thomson Reuters) Pathways for CHUK (see all 45)
        Development A2A receptor signaling
    Immune response Bacterial infections in normal airways
    Immune response MIF in innate immunity response
    Development EGFR signaling pathway
    Signal transduction AKT signaling

    Selected BioSystems Pathways for CHUK (see all 33)
        Osteopontin Signaling
    MicroRNAs in cardiomyocyte hypertrophy
    Apoptosis
    NOD pathway
    EBV LMP1 signaling

    Selected Reactome Pathways for CHUK (see all 14)
        AKT phosphorylates targets in the cytosol
    NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
    IRAK1 recruits IKK complex
    IKK complex recruitment mediated by RIP1
    FCERI mediated NF-kB activation


    Selected Kegg Pathways  (Kegg details for CHUK) (see all 32):
        MAPK signaling pathway
    Ras signaling pathway
    Chemokine signaling pathway
    NF-kappa B signaling pathway
    FoxO signaling pathway


    CHUK for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CHUK (see all 12): 
              mTOR Signaling in human mouse rat
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              Notch Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CHUK

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CHUK (O151111, 2, 3 ENSP000003594244) via UniProtKB, MINT, STRING, and/or I2D (see all 260)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HSPA1AP081073, ENSP000003648024I2D: score=1 STRING: ENSP00000364802
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    ENSG00000231555P081073I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 49):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001101response to acid ----
    GO:0002011morphogenesis of an epithelial sheet IEA--
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--
    GO:0002756MyD88-independent toll-like receptor signaling pathway TAS--

    CHUK for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for CHUK available from Tocris Bioscience    About this table
    CompoundAction CAS #
    ACHPSelective IKKalpha and IKKbeta inhibitor[406208-42-2]
    AmlexanoxInhibitor of TBK1 and IKKepsilon; antiallergic agent[68302-57-8]
    TPCA-1 Potent, selective inhibitor of IKKbeta [507475-17-4]
    IKK 16Selective inhibitor of IKK[1186195-62-9]
    PF 184Potent and selective IKKbeta inhibitor[1187460-81-6]

    2 HMDB Compounds for CHUK    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    3 DrugBank Compounds for CHUK    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Aminosalicylic Acid4-aminosalicylic acid (see all 10)65-49-6targetinhibitor11054378 11151876 12950415
    Mesalazine5-aminosalicylate (see all 4)89-57-6targetinhibitor11054378 11151876 12950415
    SulfasalazineSulfasalazin (see all 2)599-79-1targetinhibitor11054378 12950415

    Selected Novoseek inferred chemical compound relationships for CHUK gene (see all 87)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tab-2 82.7 1 15836773 (1)
    tab-1 73.4 3 10187861 (2), 17633026 (1)
    acetyl-11-keto-beta-boswellic acid 65 1 18032778 (1)
    parthenolide 61.9 7 10553091 (1), 15618150 (1), 17436572 (1), 15467918 (1) (see all 6)
    geldanamycin 59.9 11 10744744 (2), 15077173 (2), 17088896 (1), 15930313 (1) (see all 6)
    helenalin 58.5 4 20175984 (2), 20069553 (1)
    bortezomib 56 1 19436050 (1)
    ppme 54.9 1 9915837 (1)
    pdtc 49.9 9 12584727 (1), 19399830 (1), 16490171 (1), 16998220 (1) (see all 6)
    guggulsterone 47.7 1 17119390 (1)



    CHUK for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CHUK gene: 
    NM_001278.3  

    Unigene Cluster for CHUK:

    Conserved helix-loop-helix ubiquitous kinase
    Hs.198998  [show with all ESTs]
    Unigene Representative Sequence: AB209028
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000370397(uc001kqp.3) ENST00000590930 ENST00000588656 ENST00000585551

    miRNA
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    hsa-miR-323-3p hsa-miR-607 hsa-let-7d hsa-miR-374c hsa-miR-223 hsa-let-7g hsa-let-7a hsa-miR-520g
    SwitchGear 3'UTR luciferase reporter plasmidCHUK 3' UTR sequence
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    Additional mRNA sequence: 

    AB209028.1 AF009225.1 AF012890.1 AF080157.1 AY952888.2 BC034796.1 BC092514.1 U22512.1 

    8 DOTS entries:

    DT.100814684  DT.454093  DT.101978418  DT.100675447  DT.98083593  DT.92037566  DT.95162259  DT.100814686 

    Selected AceView cDNA sequences (see all 357):

    BE855521 AI968640 CK823085 BX644191 AW470642 BM703502 CN479910 BM129056 
    AI700295 CB152455 AF064093 BQ100770 AI192268 CR607760 BG027091 BQ228965 
    AA393188 BQ694986 BM695959 BC034796 BM466809 BQ023421 BG621306 AW780178 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CHUK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAACCATTCT
    CHUK Expression
    About this image

    CHUK Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CHUK Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.198998

    UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111
    Tissue specificity: Widely expressed

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CHUK (see all 12): 
              mTOR Signaling in human mouse rat
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              Notch Signaling Pathway in human mouse rat

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for CHUK gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Chuk1 , 5 conserved helix-loop-helix ubiquitous kinase1, 5 92.44(n)1
    95.3(a)1
      19 (36.71 cM)5
    126751  NM_007700.21  NP_031726.21 
     440733355 
    chicken
    (Gallus gallus)
    Aves CHUK1 conserved helix-loop-helix ubiquitous kinase 76.33(n)
    81.17(a)
      423669  NM_001012904.1  NP_001012922.1 
    lizard
    (Anolis carolinensis)
    Reptilia CHUK6
    conserved helix-loop-helix ubiquitous kinase
    79(a)
    1 ↔ 1
    GL343297.1(1220719-1262928)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.318712 Xenopus laevis transcribed sequence with moderate similarity more 79.34(n)    AW159773.1 
    zebrafish
    (Danio rerio)
    Actinopterygii zgc565392 hypothetical protein MGC56539 73.41(n)   393287  BC051614.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta ird53 antibacterial humoral response (sensu
    Invertebrata) more
    32(a)   89B3   --


    ENSEMBL Gene Tree for CHUK (if available)
    TreeFam Gene Tree for CHUK (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CHUK gene
    IKBKB2  IKBKE2  TBK12  
    7 SIMAP similar genes for CHUK using alignment to 2 protein entries:     IKKA_HUMAN (see all proteins):
    IKBKB    RPS6KA2    NUAK1    DKFZp564L2416    MARK4    CDK4
    STK11

    CHUK for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CHUK (see all 867)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 10 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs178798621,2
    C,F--101966767(-) AGATTT/-ACTTT 1 -- int12Minor allele frequency- -:0.29NS CSA 48
    rs714725291,2
    C--101971637(+) TTTTT-/T/TT  
            
    CTTTT
    1 -- int11NA 2
    rs112873651,2
    C--101983368(+) AAAAA-/AAGAAA 1 -- int12Minor allele frequency- A:0.25NA CSA 4
    rs38840831,2
    C--101983844(+) CTCTC-/CT/TC 
            
    AGATC
    1 -- int11NA 2
    rs178810841,2
    C,F--101989632(-) AAAAGA/-AAAAA 1 -- us2k11Minor allele frequency- -:0.06NS 48
    rs114417751,2
    C--101991318(+) TCAGTT/-TTTTT 1 -- us2k11Minor allele frequency- -:0.50CSA 2
    rs1817702601,2
    --102309259(+) CAGATC/GTTGCC 1 -- ds50010--------
    rs1867830371,2
    --102309296(+) AGGTAC/GCCAAT 1 -- ds50010--------
    rs38089161,2
    C,F,A,H--102309314(+) TATTAC/TTAAAA 1 -- ds500124Minor allele frequency- T:0.26NS EA NA WA CSA 2863
    rs1502150731,2
    C--102309340(+) GAAAC-/AAGAGAG 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for CHUK (101948055 - 101989376 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for CHUK (see all 21):    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv810n71CNV Loss21882294
    dgv809n71CNV Loss21882294
    nsv895924CNV Loss21882294
    nsv895922CNV Loss21882294
    nsv895947CNV Loss21882294
    dgv807n71CNV Loss21882294
    nsv895951CNV Loss21882294
    nsv895937CNV Loss21882294
    nsv895952CNV Loss21882294
    dgv808n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): CHUK
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CHUK
    DNA2.0 Custom Variant and Variant Library Synthesis for CHUK

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600664   
    OMIM disorders: 613630  
    UniProtKB/Swiss-Prot: IKKA_HUMAN, O15111
  • 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.
    Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for CHUK (see all 95):    
    About MalaCards
    cocoon syndrome    skin papilloma    multidrug-resistant tuberculosis    estrogen-receptor negative breast cancer
    salivary gland cancer    ectodermal dysplasia    hypereosinophilic syndrome    shigellosis
    human t-cell leukemia virus type 1    ataxia telangiectasia    hyperhomocysteinemia    t-cell leukemia
    papilloma    trypanosomiasis    toxoplasmosis    lung squamous cell carcinoma
    chagas disease    stomach cancer    skin disease    myeloma


    CHUK for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for CHUK gene (see all 43)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 73.6 65 11054378 (2), 17897950 (2), 9710600 (1), 10542212 (1) (see all 55)
    tumors 63.6 105 19074890 (4), 11054378 (2), 11752211 (2), 17644309 (2) (see all 74)
    leukemia t-cell 63.5 10 9710600 (1), 11064457 (1), 11726516 (1), 16611882 (1) (see all 9)
    ectodermal dysplasia, hypohidrotic 59 2 14734108 (1), 14523047 (1)
    inflammation 59 20 17371257 (2), 16009742 (1), 9520464 (1), 18163512 (1) (see all 18)
    cancer 42.3 19 19116119 (2), 18831712 (1), 19946332 (1), 17277159 (1) (see all 14)
    ataxia telangiectasia 30.2 2 17700524 (1), 16497931 (1)
    lymphoma b-cell 24.1 1 15671525 (1)
    ectodermal dysplasia 23.1 6 18633439 (4)
    lymphoma 20.4 2 17237443 (1), 20516126 (1)

    Genetic Association Database (GAD): CHUK
    Human Genome Epidemiology (HuGE) Navigator: CHUK (32 documents)

    Export disorders for CHUK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CHUK gene, integrated from 10 sources (see all 882):
    (articles sorted by number of sources associating them with CHUK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. (PubMed id 9520446)1, 2, 9 Ling L.... Goeddel D.V. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    2. The IkappaB kinase complex: master regulator of NF-kappaB signaling. (PubMed id 18626576)1, 2, 9 Solt L.A. and May M.J. (Immunol. Res. 2008)
    3. IkappaB kinase-alpha and -beta genes are coexpressed in adult and embryonic tissues but localized to different human chromosomes. (PubMed id 9813230)1, 2, 9 Hu M.C.-T. and Wang Y.-P. (Gene 1998)
    4. IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF- kappaB activation. (PubMed id 9346484)1, 2, 9 Mercurio F.... Rao A. (Science 1997)
    5. Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB. (PubMed id 17434128)1, 2, 9 Huang W.C.... Chen C.C. (Mol. Cell 2007)
    6. IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression. (PubMed id 16902410)1, 3, 9 Schneider G....Schmid R.M. (EMBO J. 2006)
    7. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. (PubMed id 9819420)1, 2, 9 Nemoto S.... Lin A. (Mol. Cell. Biol. 1998)
    8. Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. (PubMed id 20501937)1, 2, 9 Razani B.... Cheng G. (Sci. Signal. 2010)
    9. Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation. (PubMed id 12612076)1, 2, 9 Tegethoff S.... Scheidereit C. (Mol. Cell. Biol. 2003)
    10. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. (PubMed id 10195894)1, 2, 9 Delhase M.... Karin M. (Science 1999)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1147 HGNC: 1974 AceView: CHUK Ensembl:ENSG00000213341 euGenes: HUgn1147
    ECgene: CHUK Kegg: 1147 H-InvDB: CHUK

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CHUK Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CHUK Genetics and Cytogenetics in Oncology and Haematology
    SeattleSNPshttp://pga.gs.washington.edu/data/chuk/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CHUK gene:
    Search GeneIP for patents involving CHUK

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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