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Aliases for IKBKE Gene

Aliases for IKBKE Gene

  • Inhibitor Of Kappa Light Polypeptide Gene Enhancer In B-Cells, Kinase Epsilon 2 3
  • Inducible I Kappa-B Kinase 3 4
  • I-Kappa-B Kinase Epsilon 3 4
  • IKK-Epsilon 3 4
  • IKK-E 3 4
  • IKK-I 3 4
  • IKKE 3 4
  • IKKI 3 4
  • Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Epsilon 3
  • IKK-Related Kinase Epsilon 3
  • Inducible IkappaB Kinase 3
  • EC 2.7.11.10 4
  • EC 2.7.11 64
  • KIAA0151 4
  • IkBKE 4

External Ids for IKBKE Gene

Summaries for IKBKE Gene

Entrez Gene Summary for IKBKE Gene

  • 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]

GeneCards Summary for IKBKE Gene

IKBKE (Inhibitor Of Kappa Light Polypeptide Gene Enhancer In B-Cells, Kinase Epsilon) is a Protein Coding gene. Diseases associated with IKBKE include breast cancer. Among its related pathways are NF-KappaB Family Pathway and Akt Signaling. GO annotations related to this gene include protein kinase activity and IkappaB kinase activity.

UniProtKB/Swiss-Prot for IKBKE Gene

  • Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at Ser-708. Phosphorylation of STAT1 at Ser-708 seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.

Gene Wiki entry for IKBKE Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IKBKE Gene

Genomics for IKBKE Gene

Genomic Location for IKBKE Gene

Start:
206,470,243 bp from pter
End:
206,496,890 bp from pter
Size:
26,648 bases
Orientation:
Plus strand

Genomic View for IKBKE Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for IKBKE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IKBKE Gene

Proteins for IKBKE Gene

  • Protein details for IKBKE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14164-IKKE_HUMAN
    Recommended name:
    Inhibitor of nuclear factor kappa-B kinase subunit epsilon
    Protein Accession:
    Q14164
    Secondary Accessions:
    • D3DT78
    • Q3B754
    • Q3KR43
    • Q5JTS6

    Protein attributes for IKBKE Gene

    Size:
    716 amino acids
    Molecular mass:
    80462 Da
    Quaternary structure:
    • Homodimer. Interacts with MAVS/IPS1. Interacts with the adapter proteins AZI2/NAP1, TANK and TBKBP1/SINTBAD. Interacts with SIKE1. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I; interactions are disrupted by the interaction between IKBKE and SIKE1. Interacts with TOPORS; induced by DNA damage. Interacts with CYLD. Interacts (when polyubiquitinated) with IKBKB, IKBKG and MYD88. Interacts with DDX3X; the interaction is found to be induced upon virus infection. Interacts (via Protein kinase domain) with arenavirus protein N; the interaction inhibits IKBKE kinase function. Interacts with Ebola virus protein VP35; the interaction leads to inhibition of cellular antiviral response by blocking necessary interactions between the IKBKE and MAVS/IPS as well as its substrates IRF3 and IRF7.
    SequenceCaution:
    • Sequence=BAA09772.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for IKBKE Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IKBKE Gene

Proteomics data for IKBKE Gene at MOPED

Selected DME Specific Peptides for IKBKE Gene

Post-translational modifications for IKBKE Gene

  • Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation.
  • Lys-63-linked polyubiquitinated at Lys-30 and Lys-401 by TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by LPS, TNFA and interleukin-1 and required for full kinase activity and KF-kappa-B pathway activation.
  • Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys549

Other Protein References for IKBKE Gene

Domains for IKBKE Gene

Protein Domains for IKBKE Gene

UniProtKB/Swiss-Prot:

IKKE_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • Q14164
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.:
    • Q14164
genes like me logo Genes that share domains with IKBKE: view

Function for IKBKE Gene

Molecular function for IKBKE Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]
UniProtKB/Swiss-Prot Function: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at Ser-708. Phosphorylation of STAT1 at Ser-708 seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.
UniProtKB/Swiss-Prot Induction: Induced by lipopolysaccharide (LPS) and TNFA.

Enzyme Numbers (IUBMB) for IKBKE Gene

Gene Ontology (GO) - Molecular Function for IKBKE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004704 NF-kappaB-inducing kinase activity IDA 10882136
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 14743216
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with IKBKE: view
genes like me logo Genes that share phenotypes with IKBKE: view

Animal Models for IKBKE Gene

MGI Knock Outs for IKBKE:

miRNA for IKBKE Gene

miRTarBase miRNAs that target IKBKE

No data available for Transcription Factor Targeting and HOMER Transcription for IKBKE Gene

Localization for IKBKE Gene

Subcellular locations from UniProtKB/Swiss-Prot for IKBKE Gene

Cytoplasm. Nucleus. Nucleus, PML body. Note=Targeting to PML nuclear bodies upon DNA damage is TOPORS-dependent.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IKBKE Gene COMPARTMENTS Subcellular localization image for IKBKE gene
Compartment Confidence
nucleus 5
cytosol 4
endosome 4
peroxisome 1

Gene Ontology (GO) - Cellular Components for IKBKE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 20188669
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0010008 endosome membrane TAS --
genes like me logo Genes that share ontologies with IKBKE: view

Pathways for IKBKE Gene

genes like me logo Genes that share pathways with IKBKE: view

Gene Ontology (GO) - Biological Process for IKBKE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
GO:0006468 protein phosphorylation IDA 10882136
GO:0006955 immune response NAS 10421793
GO:0007252 I-kappaB phosphorylation IEA --
genes like me logo Genes that share ontologies with IKBKE: view

Compounds for IKBKE Gene

(2) HMDB Compounds for IKBKE Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(9) Novoseek inferred chemical compound relationships for IKBKE Gene

Compound -log(P) Hits PubMed IDs
rantes 47.2 2
poly(i-c) 44.8 1
serine 25.6 5
threonine 22.7 3
phosphatidylinositol 7 1
genes like me logo Genes that share compounds with IKBKE: view

Transcripts for IKBKE Gene

Unigene Clusters for IKBKE Gene

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IKBKE Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1:
SP2:
SP3:
SP4: - -
SP5:

Relevant External Links for IKBKE Gene

GeneLoc Exon Structure for
IKBKE
ECgene alternative splicing isoforms for
IKBKE

Expression for IKBKE Gene

mRNA expression in normal human tissues for IKBKE Gene

mRNA differential expression in normal tissues according to GTEx for IKBKE Gene

This gene is overexpressed in Whole Blood (6.9).

Integrated Proteomics: protein expression from ProteomicsDB and MOPED for IKBKE Gene

SOURCE GeneReport for Unigene cluster for IKBKE Gene Hs.321045

mRNA Expression by UniProt/SwissProt for IKBKE Gene

Q14164-IKKE_HUMAN
Tissue specificity: Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon
genes like me logo Genes that share expressions with IKBKE: view

Orthologs for IKBKE Gene

This gene was present in the common ancestor of chordates.

Orthologs for IKBKE Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia IKBKE 36
  • 87.76 (n)
  • 88.27 (a)
dog
(Canis familiaris)
Mammalia IKBKE 36
  • 89.44 (n)
  • 90.53 (a)
mouse
(Mus musculus)
Mammalia Ikbke 36
  • 83.01 (n)
  • 83.99 (a)
Ikbke 16
rat
(Rattus norvegicus)
Mammalia Ikbke 36
  • 83.1 (n)
  • 83.85 (a)
chicken
(Gallus gallus)
Aves IKBKE 36
  • 69.47 (n)
  • 64.1 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia ikbke 36
  • 61.73 (n)
  • 58.36 (a)
zebrafish
(Danio rerio)
Actinopterygii ikbke 36
  • 56.6 (n)
  • 49.72 (a)
wufk70c05 36
Species with no ortholog for IKBKE:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for IKBKE Gene

ENSEMBL:
Gene Tree for IKBKE (if available)
TreeFam:
Gene Tree for IKBKE (if available)

Paralogs for IKBKE Gene

Selected SIMAP similar genes for IKBKE Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with IKBKE: view

No data available for Paralogs for IKBKE Gene

Variants for IKBKE Gene

Sequence variations from dbSNP and Humsavar for IKBKE Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs10836 -- 206,496,836(+) GGGCA(C/G)GTCCA utr-variant-3-prime
rs15672 -- 206,496,625(+) TCTCC(A/G)CTCCC utr-variant-3-prime, downstream-variant-500B
rs944774 -- 206,495,803(-) GGAGG(G/T)GAAAG intron-variant
rs944775 -- 206,495,260(-) CACGC(A/G)GTTGG intron-variant
rs944776 -- 206,485,626(-) GGACC(C/T)ACCCA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for IKBKE Gene

Variant ID Type Subtype PubMed ID
dgv521n71 CNV Loss 21882294
dgv522n71 CNV Gain 21882294

Relevant External Links for IKBKE Gene

HapMap Linkage Disequilibrium report
IKBKE
Human Gene Mutation Database (HGMD)
IKBKE

Disorders for IKBKE Gene

(1) MalaCards Diseases for IKBKE Gene

Search for IKBKE Gene in MalaCards »

(11) Novoseek inferred disease relationships for IKBKE Gene

Disease -log(P) Hits PubMed IDs
virus infection 50.2 6
necrosis 44.1 8
leukemia t-cell 32.3 2
tumors 25.5 12
rheumatoid arthritis 13.3 1

Relevant External Links for IKBKE

Genetic Association Database (GAD)
IKBKE
Human Genome Epidemiology (HuGE) Navigator
IKBKE
genes like me logo Genes that share disorders with IKBKE: view

No data available for UniProtKB/Swiss-Prot for IKBKE Gene

Publications for IKBKE Gene

  1. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus- triggered IRF-3 activation pathways. (PMID: 16281057) Huang J. … Shu H.-B. (EMBO J. 2005) 3 4 23
  2. SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. (PMID: 20188669) Renner F. … Schmitz M.L. (Mol. Cell 2010) 3 4 23
  3. IKK epsilon is part of a novel PMA-inducible IkappaB kinase complex. (PMID: 10882136) Peters R.T. … Maniatis T. (Mol. Cell 2000) 2 3 4
  4. IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. (PMID: 10421793) Shimada T. … Akira S. (Int. Immunol. 1999) 2 3 4
  5. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. (PMID: 8590280) Nagase T. … Nomura N. (DNA Res. 1995) 3 4

Products for IKBKE Gene

  • Addgene plasmids for IKBKE

Sources for IKBKE Gene

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