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NameInhibitor of nuclear factor kappa-B kinase subunit epsilon
Synonyms
  • 2.7.11.10
  • I-kappa-B kinase epsilon
  • IKK-i
  • IKKE
  • IKKI
  • Inducible I kappa-B kinase
  • KIAA0151
Gene NameIKBKE
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008831|Inhibitor of nuclear factor kappa-B kinase subunit epsilon
MQSTANYLWHTDDLLGQGATASVYKARNKKSGELVAVKVFNTTSYLRPREVQVREFEVLR
KLNHQNIVKLFAVEETGGSRQKVLVMEYCSSGSLLSVLESPENAFGLPEDEFLVVLRCVV
AGMNHLRENGIVHRDIKPGNIMRLVGEEGQSIYKLTDFGAARELDDDEKFVSVYGTEEYL
HPDMYERAVLRKPQQKAFGVTVDLWSIGVTLYHAATGSLPFIPFGGPRRNKEIMYRITTE
KPAGAIAGAQRRENGPLEWSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWGFDQFFA
ETSDILQRVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCV
LEPSVSAQHIAHTTASSPLTLFSTAIPKGLAFRDPALDVPKFVPKVDLQADYNTAKGVLG
AGYQALRLARALLDGQELMFRGLHWVMEVLQATCRRTLEVARTSLLYLSSSLGTERFSSV
AGTPEIQELKAAAELRSRLRTLAEVLSRCSQNITETQESLSSLNRELVKSRDQVHEDRSI
QQIQCCLDKMNFIYKQFKKSRMRPGLGYNEEQIHKLDKVNFSHLAKRLLQVFQEECVQKY
QASLVTHGKRMRVVHETRNHLRLVGCSVAACNTEAQGVQESLSKLLEELSHQLLQDRAKG
AQASPPPIAPYPSPTRKDLLLHMQELCEGMKLLASDLLDNNRIIERLNRVPAPPDV
Number of residues716
Molecular Weight80461.665
Theoretical pINot Available
GO Classification
Functions
  • ATP binding
  • IkappaB kinase activity
  • K48-linked polyubiquitin binding
  • NF-kappaB-inducing kinase activity
  • ubiquitin protein ligase binding
Processes
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • MyD88-independent toll-like receptor signaling pathway
  • toll-like receptor 3 signaling pathway
  • toll-like receptor 4 signaling pathway
  • toll-like receptor signaling pathway
  • TRIF-dependent toll-like receptor signaling pathway
  • immune response
  • cellular response to virus
  • innate immune response
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • negative regulation of type I interferon production
  • protein phosphorylation
  • response to interferon-beta
  • response to type I interferon
  • protein homooligomerization
  • NIK/NF-kappaB signaling
Components
  • cytoplasm
  • nucleus
  • mitochondrial membrane
  • PML body
  • cytosol
  • endosome membrane
General FunctionUbiquitin protein ligase binding
Specific FunctionSerine/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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ14164
UniProtKB Entry NameIKKE_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013442|Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)
ATGGAGTACTGCTCCAGTGGGAGCCTGCTGAGTGTGCTGGAGAGCCCTGAGAATGCCTTT
GGGCTGCCTGAGGATGAGTTCCTGGTGGTGCTGCGCTGTGTGGTGGCCGGCATGAACCAC
CTGCGGGAGAACGGCATTGTGCATCGCGACATCAAGCCGGGGAACATCATGCGCCTCGTA
GGGGAGGAGGGGCAGAGCATCTACAAGCTGACAGACTTCGGCGCTGCCCGGGAGCTGGAT
GATGATGAGAAGTTCGTCTCGGTCTATGGGACTGAGGAGTACCTGCATCCCGACATGTAT
GAGCGGGCGGTGCTTCGAAAGCCCCAGCAAAAAGCGTTCGGGGTGACTGTGGATCTCTGG
AGCATTGGAGTGACCTTGTACCATGCAGCCACTGGCAGCCTGCCCTTCATCCCCTTTGGT
GGGCCACGGCGGAACAAGGAGATCATGTACCGGATCACCACGGAGAAGCCGGCTGGGGCC
ATTGCAGGTGCCCAGAGGCGGGAGAACGGGCCCCTGGAGTGGAGCTACACCCTCCCCATC
ACCTGCCAGCTGTCACTGGGGCTGCAGAGCCAGCTGGTGCCCATCCTGGCCAACATCCTG
GAGGTGGAGCAGGCCAAGTGCTGGGGCTTCGACCAGTTCTTTGCGGAGACCAGTGACATC
CTGCAGCGAGTTGTCGTCCATGTCTTCTCCCTGTCCCAGGCAGTCCTGCACCACATCTAT
ATCCATGCCCACAACACGATAGCCATTTTCCAGGAGGCCGTGCACAAGCAGACCAGTGTG
GCCCCCCGACACCAGGAGTACCTCTTTGAGGGTCACCTCTGTGTCCTCGAGCCCAGCGTC
TCAGCACAGCACATCGCCCACACGACGGCAAGCAGCCCCCTGACCCTCTTCAGCACAGCC
ATCCCTAAGGGGCTGGCCTTCAGGGACCCTGCTCTGGACGTCCCCAAGTTCGTCCCCAAA
GTGGACCTGCAGGCGGATTACAACACTGCCAAGGGCGTGTTGGGCGCCGGCTACCAGGCC
CTGCGGCTGGCACGGGCCCTGCTGGATGGGCAGGAGCTAATGTTTCGGGGGCTGCACTGG
GTCATGGAGGTGCTCCAGGCCACATGCAGACGGACTCTGGAAGTGGCAAGGACATCCCTC
CTCTACCTCAGCAGCAGCCTGGGAACTGAGAGGTTCAGCAGCGTGGCTGGAACGCCTGAG
ATCCAGGAACTGAAGGCGGCTGCAGAACTGAGGTCCAGGCTGCGGACTCTAGCGGAGGTC
CTCTCCAGATGCTCCCAAAATATCACGGAGACCCAGGAGAGCCTGAGCAGCCTGAACCGG
GAGCTGGTGAAGAGCCGGGATCAGGTACATGAGGACAGAAGCATCCAGCAGATTCAGTGC
TGTTTGGACAAGATGAACTTCATCTACAAACAGTTCAAGAAGTCTAGGATGAGGCCAGGG
CTTGGCTACAACGAGGAGCAGATTCACAAGCTGGATAAGGTGAATTTCAGTCATTTAGCC
AAAAGACTCCTGCAGGTGTTCCAGGAGGAGTGCGTGCAGAAGTATCAAGCGTCCTTAGTC
ACACACGGCAAGAGGATGAGGGTGGTGCACGAGACCAGGAACCACCTGCGCCTGGTTGGC
TGTTCTGTGGCTGCCTGTAACACAGAAGCCCAGGGGGTCCAGGAGAGTCTCAGCAAGCTC
CTGGAAGAGCTATCTCACCAGCTCCTTCAGGACCGAGCAAAGGGGGCTCAGGCCTCGCCG
CCTCCCATAGCTCCTTACCCCAGCCCTACACGAAAGGACCTGCTTCTCCACATGCAAGAG
CTCTGCGAGGGGATGAAGCTGCTGGCATCTGACCTCCTGGACAACAACCGCATCATCGAA
CGGCTAAATAGAGTCCCAGCACCTCCTGATGTCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:14552
Chromosome Location1
LocusNot Available
References
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