Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q14164 (IKKE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inhibitor of nuclear factor kappa-B kinase subunit epsilon

Short name=I-kappa-B kinase epsilon
Short name=IKK-E
Short name=IKK-epsilon
Short name=IkBKE
EC=2.7.11.10
Alternative name(s):
Inducible I kappa-B kinase
Short name=IKK-i
Gene names
Name:IKBKE
Synonyms:IKKE, IKKI, KIAA0151
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length716 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12 Ref.13 Ref.16 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24

Catalytic activity

ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].

Subunit 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 poylubiquitinated) 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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.22 Ref.23 Ref.24

Subcellular location

Cytoplasm. Nucleus. NucleusPML body. Note: Targeting to PML nuclear bodies upon DNA damage is TOPORS-dependent. Ref.18 Ref.21

Tissue specificity

Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon.

Induction

Induced by lipopolysaccharide (LPS) and TNFA. Ref.23

Post-translational modification

Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation. Ref.16 Ref.20 Ref.24

Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1. Ref.18

'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.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAA09772.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processDNA damage
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

NIK/NF-kappaB signaling

Inferred from direct assay Ref.2. Source: GOC

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

immune response

Non-traceable author statement Ref.1. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.2Ref.18. Source: UniProtKB

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentPML body

Inferred from direct assay Ref.18. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.18. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.18. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

IkappaB kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

NF-kappaB-inducing kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10Ref.15Ref.18. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14164-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q14164-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 716716Inhibitor of nuclear factor kappa-B kinase subunit epsilon
PRO_0000086017

Regions

Domain9 – 315307Protein kinase
Nucleotide binding15 – 239ATP By similarity
Region383 – 647265Interaction with DDX3X
Region436 – 45722Leucine-zipper

Sites

Active site1351Proton acceptor By similarity
Binding site381ATP Probable

Amino acid modifications

Modified residue1721Phosphoserine; by autocatalysis and IKKB Ref.24
Modified residue5011Phosphothreonine By similarity
Modified residue6641Phosphoserine Ref.17
Cross-link30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23
Cross-link231Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.18
Cross-link401Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23

Natural variations

Alternative sequence1 – 8585Missing in isoform 2.
VSP_044305
Natural variant1281E → K. Ref.4
Corresponds to variant rs41296028 [ dbSNP | Ensembl ].
VAR_038816
Natural variant3711A → T. Ref.4 Ref.25
Corresponds to variant rs17021877 [ dbSNP | Ensembl ].
VAR_038817
Natural variant4831T → M. Ref.25
Corresponds to variant rs52817862 [ dbSNP | Ensembl ].
VAR_040571
Natural variant5151E → D. Ref.4
Corresponds to variant rs41299015 [ dbSNP | Ensembl ].
VAR_038818
Natural variant5431I → M. Ref.4
Corresponds to variant rs41299037 [ dbSNP | Ensembl ].
VAR_038819
Natural variant6021A → V. Ref.4 Ref.25
Corresponds to variant rs12059562 [ dbSNP | Ensembl ].
VAR_038820
Natural variant6601G → E. Ref.25
Corresponds to variant rs55822317 [ dbSNP | Ensembl ].
VAR_040572
Natural variant7131P → L. Ref.4 Ref.25
Corresponds to variant rs3748022 [ dbSNP | Ensembl ].
VAR_019989

Experimental info

Mutagenesis301K → A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization. Ref.23
Mutagenesis301K → R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization. Ref.23
Mutagenesis381K → A: Loss of kinase activity and loss of nuclear import. Ref.1
Mutagenesis1681E → A: Slight decrease of kinase activity. Ref.1
Mutagenesis1721S → A: Loss of autophosphorylation and of kinase activity. Ref.1
Mutagenesis1721S → E: Decrease in kinase activity. Ref.1
Mutagenesis2311K → R: Loss of sumoylation and loss of targeting to nuclear bodies. Ref.18
Mutagenesis4011K → A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization. Ref.23
Mutagenesis4011K → R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization. Ref.23
Mutagenesis4161K → A: No effect on ubiquitination. Ref.23
Mutagenesis4161K → R: No effect on ubiquitination. Ref.23
Sequence conflict1871R → Q in AAI05925. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 3E5FBE5840734D81

FASTA71680,462
        10         20         30         40         50         60 
MQSTANYLWH TDDLLGQGAT ASVYKARNKK SGELVAVKVF NTTSYLRPRE VQVREFEVLR 

        70         80         90        100        110        120 
KLNHQNIVKL FAVEETGGSR QKVLVMEYCS SGSLLSVLES PENAFGLPED EFLVVLRCVV 

       130        140        150        160        170        180 
AGMNHLRENG IVHRDIKPGN IMRLVGEEGQ SIYKLTDFGA ARELDDDEKF VSVYGTEEYL 

       190        200        210        220        230        240 
HPDMYERAVL RKPQQKAFGV TVDLWSIGVT LYHAATGSLP FIPFGGPRRN KEIMYRITTE 

       250        260        270        280        290        300 
KPAGAIAGAQ RRENGPLEWS YTLPITCQLS LGLQSQLVPI LANILEVEQA KCWGFDQFFA 

       310        320        330        340        350        360 
ETSDILQRVV VHVFSLSQAV LHHIYIHAHN TIAIFQEAVH KQTSVAPRHQ EYLFEGHLCV 

       370        380        390        400        410        420 
LEPSVSAQHI AHTTASSPLT LFSTAIPKGL AFRDPALDVP KFVPKVDLQA DYNTAKGVLG 

       430        440        450        460        470        480 
AGYQALRLAR ALLDGQELMF RGLHWVMEVL QATCRRTLEV ARTSLLYLSS SLGTERFSSV 

       490        500        510        520        530        540 
AGTPEIQELK AAAELRSRLR TLAEVLSRCS QNITETQESL SSLNRELVKS RDQVHEDRSI 

       550        560        570        580        590        600 
QQIQCCLDKM NFIYKQFKKS RMRPGLGYNE EQIHKLDKVN FSHLAKRLLQ VFQEECVQKY 

       610        620        630        640        650        660 
QASLVTHGKR MRVVHETRNH LRLVGCSVAA CNTEAQGVQE SLSKLLEELS HQLLQDRAKG 

       670        680        690        700        710 
AQASPPPIAP YPSPTRKDLL LHMQELCEGM KLLASDLLDN NRIIERLNRV PAPPDV 

« Hide

Isoform 2 [UniParc].

Checksum: 1E6CC6C29C88897D
Show »

FASTA63170,816

References

« Hide 'large scale' references
[1]"IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases."
Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y., Kanamaru A., Akira S.
Int. Immunol. 11:1357-1362(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-38; GLU-168 AND SER-172.
[2]"IKK epsilon is part of a novel PMA-inducible IkappaB kinase complex."
Peters R.T., Liao S.-M., Maniatis T.
Mol. Cell 5:513-522(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Leukocyte.
[3]"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."
Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.
DNA Res. 2:167-174(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Bone marrow.
[4]SeattleSNPs variation discovery resource
Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-128; THR-371; ASP-515; MET-543; VAL-602 AND LEU-713.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[8]"Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling."
Fujita F., Taniguchi Y., Kato T., Narita Y., Furuya A., Ogawa T., Sakurai H., Joh T., Itoh M., Delhase M., Karin M., Nakanishi M.
Mol. Cell. Biol. 23:7780-7793(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AZI2.
[9]"Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways."
Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.
J. Biol. Chem. 279:15652-15661(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TICAM1.
[10]"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."
Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.
EMBO J. 24:4018-4028(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIKE1; IRF3; TICAM1 AND DDX58.
[11]"Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus."
Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., Bartenschlager R., Tschopp J.
Nature 437:1167-1172(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAVS.
[12]"SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK."
Ryzhakov G., Randow F.
EMBO J. 26:3180-3190(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AZI2; TANK AND TBKBP1.
[13]"The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response."
Soulat D., Burckstummer T., Westermayer S., Goncalves A., Bauch A., Stefanovic A., Hantschel O., Bennett K.L., Decker T., Superti-Furga G.
EMBO J. 27:2135-2146(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF DDX3X.
[14]"Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation."
Schroder M., Baran M., Bowie A.G.
EMBO J. 27:2147-2157(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX3X.
[15]"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response."
Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R., Ting A.T.
EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CYLD.
[16]"Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1."
Prins K.C., Cardenas W.B., Basler C.F.
J. Virol. 83:3069-3077(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IRF3 PHOSPHORYLATION, INTERACTION WITH EBOLAVIRUS PROTEIN VP35, AUTOPHOSPHORYLATION.
[17]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death."
Renner F., Moreno R., Schmitz M.L.
Mol. Cell 37:503-515(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TOPORS, SUMOYLATION AT LYS-231 BY TOPORS, DESUMOYLATION BY SENP1, MUTAGENESIS OF LYS-231, SUBCELLULAR LOCATION.
[19]"Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion."
Wang H., Ryu W.S.
PLoS Pathog. 6:E1000986-E1000986(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX3X.
[20]"Novel cross-talk within the IKK family controls innate immunity."
Clark K., Peggie M., Plater L., Sorcek R.J., Young E.R., Madwed J.B., Hough J., McIver E.G., Cohen P.
Biochem. J. 434:93-104(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION BY IKBKB/IKKB.
[21]"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation."
Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y., Guan K.L.
Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AKT PHOSPHORYLATION, SUBCELLULAR LOCATION.
[22]"Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKKepsilon."
Pythoud C., Rodrigo W.W., Pasqual G., Rothenberger S., Martinez-Sobrido L., de la Torre J.C., Kunz S.
J. Virol. 86:7728-7738(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARENAVIRUS PROTEIN N.
[23]"IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex."
Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.
Cell Rep. 3:724-733(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HOMODIMER, INTERACTION WITH IKBKB; IKBKG AND MYD88, INDUCTION BY LPS, UBIQUITINATION AT LYS-30 AND LYS-401, MUTAGENESIS OF LYS-30; LYS-401 AND LYS-416.
[24]"Human DEAD box helicase 3 couples IkappaB kinase epsilon to interferon regulatory factor 3 activation."
Gu L., Fullam A., Brennan R., Schroder M.
Mol. Cell. Biol. 33:2004-2015(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DDX3X AND IRF3 PHOSPHORYLATION, INTERACTION WITH DDX3X AND IRF3, PHOSPHORYLATION AT SER-172.
[25]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371; MET-483; VAL-602; GLU-660 AND LEU-713.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D63485 mRNA. Translation: BAA09772.2. Different initiation.
AB016590 mRNA. Translation: BAA85155.1.
AF241789 mRNA. Translation: AAF45307.1.
DQ667176 Genomic DNA. Translation: ABG25921.1.
AL354681 Genomic DNA. Translation: CAI15250.1.
CH471100 Genomic DNA. Translation: EAW93549.1.
BC105923 mRNA. Translation: AAI05924.1.
BC105924 mRNA. Translation: AAI05925.1.
BC107812 mRNA. Translation: AAI07813.1.
CCDSCCDS30996.1. [Q14164-1]
CCDS53464.1. [Q14164-2]
RefSeqNP_001180250.1. NM_001193321.1. [Q14164-2]
NP_001180251.1. NM_001193322.1.
NP_054721.1. NM_014002.3. [Q14164-1]
XP_005273413.1. XM_005273356.2. [Q14164-1]
UniGeneHs.321045.

3D structure databases

ProteinModelPortalQ14164.
SMRQ14164. Positions 2-621.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115000. 61 interactions.
DIPDIP-27530N.
IntActQ14164. 18 interactions.
MINTMINT-1132084.
STRING9606.ENSP00000356087.

Chemistry

BindingDBQ14164.
ChEMBLCHEMBL3038486.
GuidetoPHARMACOLOGY2040.

PTM databases

PhosphoSiteQ14164.

Polymorphism databases

DMDM14548079.

Proteomic databases

MaxQBQ14164.
PaxDbQ14164.
PRIDEQ14164.

Protocols and materials databases

DNASU9641.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367120; ENSP00000356087; ENSG00000143466. [Q14164-1]
ENST00000537984; ENSP00000444529; ENSG00000143466. [Q14164-2]
ENST00000581977; ENSP00000464030; ENSG00000263528. [Q14164-1]
ENST00000584998; ENSP00000462396; ENSG00000263528. [Q14164-2]
GeneID9641.
KEGGhsa:9641.
UCSCuc001hdz.2. human. [Q14164-1]

Organism-specific databases

CTD9641.
GeneCardsGC01P206643.
H-InvDBHIX0116011.
HGNCHGNC:14552. IKBKE.
HPACAB025983.
HPA015788.
MIM605048. gene.
neXtProtNX_Q14164.
PharmGKBPA134962294.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000220867.
HOVERGENHBG008494.
InParanoidQ14164.
KOK07211.
OMAHIYIHAH.
OrthoDBEOG7Z95KH.
PhylomeDBQ14164.
TreeFamTF324269.

Enzyme and pathway databases

BRENDA2.7.11.10. 2681.
ReactomeREACT_6900. Immune System.
SABIO-RKQ14164.
SignaLinkQ14164.

Gene expression databases

BgeeQ14164.
CleanExHS_IKBKE.
GenevestigatorQ14164.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIKBKE. human.
GeneWikiIKBKE.
GenomeRNAi9641.
NextBio36191.
PROQ14164.
SOURCESearch...

Entry information

Entry nameIKKE_HUMAN
AccessionPrimary (citable) accession number: Q14164
Secondary accession number(s): D3DT78 expand/collapse secondary AC list , Q3B754, Q3KR43, Q5JTS6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM