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IKBKE inhibitor of nuclear factor kappa B kinase subunit epsilon [ Homo sapiens (human) ]

Gene ID: 9641, updated on 17-Jun-2019

Summary

Official Symbol
IKBKEprovided by HGNC
Official Full Name
inhibitor of nuclear factor kappa B kinase subunit epsilonprovided by HGNC
Primary source
HGNC:HGNC:14552
See related
Ensembl:ENSG00000263528 MIM:605048
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IKKE; IKKI; IKK-E; IKK-i
Summary
IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).[supplied by OMIM, Oct 2009]
Expression
Broad expression in lymph node (RPKM 9.0), appendix (RPKM 7.5) and 20 other tissues See more
Orthologs

Genomic context

See IKBKE in Genome Data Viewer
Location:
1q32.1
Exon count:
22
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (206470243..206496890)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (206643586..206670223)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372873 Neighboring gene ribosomal protein L22 pseudogene 4 Neighboring gene family with sequence similarity 72 member A Neighboring gene SLIT-ROBO Rho GTPase activating protein 2 Neighboring gene microRNA 6769b Neighboring gene Ras association domain family member 5 Neighboring gene ribosomal protein L7a pseudogene 20 Neighboring gene eukaryotic translation initiation factor 2D

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120/CD4 interaction-induced NF-kappaB activation stimulates the hyperphosphorylation of IkappaB-alpha by IkappaB kinases (IKKs) PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
    Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
  • Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystem (from REACTOME)
    Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystemCell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and tran...
  • Cardiac Hypertrophic Response, organism-specific biosystem (from WikiPathways)
    Cardiac Hypertrophic Response, organism-specific biosystemIntegrated schematic of the more extensively characterized intracellular signal-transduction pathways that coordinate the cardiac hypertrophic response. During development and in response to physiolo...
  • Cytosolic DNA-sensing pathway, organism-specific biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • Cytosolic DNA-sensing pathway, conserved biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • Hepatitis B, organism-specific biosystem (from KEGG)
    Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
  • Hepatitis C, organism-specific biosystem (from KEGG)
    Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Hepatitis C, conserved biosystem (from KEGG)
    Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • IL-17 signaling pathway, organism-specific biosystem (from KEGG)
    IL-17 signaling pathway, organism-specific biosystemThe interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defi...
  • IL-17 signaling pathway, conserved biosystem (from KEGG)
    IL-17 signaling pathway, conserved biosystemThe interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defi...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
    MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
  • MyD88-independent TLR3/TLR4 cascade, organism-specific biosystem (from REACTOME)
    MyD88-independent TLR3/TLR4 cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
  • NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
    NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystem (from REACTOME)
    Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystemAs with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune...
  • RIG-I-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    RIG-I-like Receptor Signaling, organism-specific biosystemViral pathogen RNA are recognized by host helicases called RIG-I-like receptors (RLRs) that include DDX58 (RIG-I), DHX58 (LGP2), IFIH1 (MDA5), SNW1, and DDX17. These RLR proteins then go on to initia...
  • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystem (from REACTOME)
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystemRIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. F...
  • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Regulation of toll-like receptor signaling pathway, organism-specific biosystem
    Regulation of toll-like receptor signaling pathway
  • TLR4 Signaling and Tolerance, organism-specific biosystem (from WikiPathways)
    TLR4 Signaling and Tolerance, organism-specific biosystemThis pathway is based on the figure 2 of "Toll-like Receptors: Novel Pharmacological Targets for the Treatment of Neurological Diseases" and figure 2 of "Toll-like receptor and its roles in myocardia...
  • TRAF3-dependent IRF activation pathway, organism-specific biosystem (from REACTOME)
    TRAF3-dependent IRF activation pathway, organism-specific biosystemIPS-1/MAVS/Cardif/VISA with its TRAF-interaction motif (TIM) directly interacts with TRAF3 and recruits TRAF3 to the RIG-I/MDA5 signaling complex. TRAF3 acts as a scaffold for the assembly of a signa...
  • TRAF6 mediated IRF7 activation, organism-specific biosystem (from REACTOME)
    TRAF6 mediated IRF7 activation, organism-specific biosystemTRAF6 is crucial for both RIG-I- and MDA5-mediated antiviral responses. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of type I IFNs and IL...
  • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
    TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
  • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
  • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
  • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
    Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
  • Toll-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    Toll-like Receptor Signaling, organism-specific biosystemThis pathway is based on the figure 1 of "Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control study" (see bibliography). TLR and NFkB are important in inflamma...
  • Toll-like Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Toll-like Receptor Signaling Pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
    Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0151, MGC125294, MGC125295, MGC125297

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
IkappaB kinase activity IEA
Inferred from Electronic Annotation
more info
 
K48-linked polyubiquitin modification-dependent protein binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
NOT K63-linked polyubiquitin modification-dependent protein binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
NF-kappaB-inducing kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity TAS
Traceable Author Statement
more info
 
protein phosphatase binding ISS
Inferred from Sequence or Structural Similarity
more info
 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
I-kappaB phosphorylation IEA
Inferred from Electronic Annotation
more info
 
NIK/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
TRIF-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
cellular response to virus IEA
Inferred from Electronic Annotation
more info
 
immune response NAS
Non-traceable Author Statement
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of type I interferon production TAS
Traceable Author Statement
more info
 
peptidyl-serine phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
Inferred from Expression Pattern
more info
PubMed 
positive regulation of lipid storage ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of type I interferon-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
protein homooligomerization IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
response to interferon-beta IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to type I interferon IEA
Inferred from Electronic Annotation
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
PML body IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endosome membrane TAS
Traceable Author Statement
more info
 
mitochondrial membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
inhibitor of nuclear factor kappa-B kinase subunit epsilon
Names
I-kappa-B kinase epsilon
IKK-epsilon
IKK-related kinase epsilon
inducible I kappa-B kinase
inducible IkappaB kinase
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
NP_001180250.1
NP_001180251.1
NP_054721.1
XP_005273413.1
XP_016858357.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001193321.2NP_001180250.1  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 3

    See identical proteins and their annotated locations for NP_001180250.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks an alternate segment which results in the use of a downstream start codon, compared to variant 1. The resulting protein (isoform 3) is shorter when it is compared to isoform 1.
    Source sequence(s)
    BC107812, CB243308, D63485, DA999897
    Consensus CDS
    CCDS53464.1
    UniProtKB/Swiss-Prot
    Q14164
    Related
    ENSP00000462396.1, ENST00000584998.5
    Conserved Domains (2) summary
    cd12219
    Location:212298
    UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
    cl21453
    Location:1245
    PKc_like; Protein Kinases, catalytic domain
  2. NM_001193322.2NP_001180251.1  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate segment in the 3' coding region, which shifts the reading frame, compared to variant 1. The resulting protein (isoform 2) has a shorter and distinct C-terminus when it is compared to isoform 1.
    Source sequence(s)
    BC107591, CB243308, D63485, DA999897, DB152295
    Consensus CDS
    CCDS73019.1
    UniProtKB/Swiss-Prot
    Q14164
    UniProtKB/TrEMBL
    A0A075B7B4
    Related
    ENSP00000473833.1, ENST00000578328.6
    Conserved Domains (3) summary
    smart00220
    Location:9242
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd12219
    Location:297383
    UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
    cl21453
    Location:15330
    PKc_like; Protein Kinases, catalytic domain
  3. NM_014002.4NP_054721.1  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform 1

    See identical proteins and their annotated locations for NP_054721.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) is the longest transcript and it encodes the longest protein (isoform 1).
    Source sequence(s)
    BC105923, CB243308, D63485, DA990116, DB152295
    Consensus CDS
    CCDS30996.1
    UniProtKB/Swiss-Prot
    Q14164
    Related
    ENSP00000464030.1, ENST00000581977.7
    Conserved Domains (2) summary
    cd12219
    Location:297383
    UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
    cl21453
    Location:15330
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    206470243..206496890
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005273356.2XP_005273413.1  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1

    See identical proteins and their annotated locations for XP_005273413.1

    UniProtKB/Swiss-Prot
    Q14164
    Conserved Domains (2) summary
    cd12219
    Location:297383
    UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
    cl21453
    Location:15330
    PKc_like; Protein Kinases, catalytic domain
  2. XM_017002868.1XP_016858357.1  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X2

RNA

  1. XR_922002.2 RNA Sequence

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