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Protein

Inhibitor of nuclear factor kappa-B kinase subunit epsilon

Gene

IKBKE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 AKT1.9 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei38 – 381ATPCurated
Active sitei135 – 1351Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – 239ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • IkappaB kinase activity Source: UniProtKB-EC
  • NF-kappaB-inducing kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

DNA damage

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.10. 2681.
ReactomeiREACT_24938. TRAF6 mediated IRF7 activation.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
SABIO-RKQ14164.
SignaLinkiQ14164.

Names & Taxonomyi

Protein namesi
Recommended name:
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (EC:2.7.11.10)
Short name:
I-kappa-B kinase epsilon
Short name:
IKK-E
Short name:
IKK-epsilon
Short name:
IkBKE
Alternative name(s):
Inducible I kappa-B kinase
Short name:
IKK-i
Gene namesi
Name:IKBKE
Synonyms:IKKE, IKKI, KIAA0151
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:14552. IKBKE.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endosome membrane Source: Reactome
  • mitochondrial membrane Source: AgBase
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi30 – 301K → A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization. 1 Publication
Mutagenesisi30 – 301K → R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization. 1 Publication
Mutagenesisi38 – 381K → A: Loss of kinase activity and loss of nuclear import. 1 Publication
Mutagenesisi168 – 1681E → A: Slight decrease of kinase activity. 1 Publication
Mutagenesisi172 – 1721S → A: Loss of autophosphorylation and of kinase activity. 1 Publication
Mutagenesisi172 – 1721S → E: Decrease in kinase activity. 1 Publication
Mutagenesisi231 – 2311K → R: Loss of sumoylation and loss of targeting to nuclear bodies. 1 Publication
Mutagenesisi401 – 4011K → A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization. 1 Publication
Mutagenesisi401 – 4011K → R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization. 1 Publication
Mutagenesisi416 – 4161K → A: No effect on ubiquitination. 1 Publication
Mutagenesisi416 – 4161K → R: No effect on ubiquitination. 1 Publication

Organism-specific databases

PharmGKBiPA134962294.

Polymorphism and mutation databases

BioMutaiIKBKE.
DMDMi14548079.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 716716Inhibitor of nuclear factor kappa-B kinase subunit epsilonPRO_0000086017Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki30 – 30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei172 – 1721Phosphoserine; by autocatalysis and IKKB1 Publication
Cross-linki231 – 231Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
Cross-linki401 – 401Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei501 – 5011Phosphothreonine1 Publication
Modified residuei664 – 6641Phosphoserine1 Publication

Post-translational modificationi

Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation.2 Publications
Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1.1 Publication
'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.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ14164.
PaxDbiQ14164.
PRIDEiQ14164.

PTM databases

PhosphoSiteiQ14164.

Expressioni

Tissue specificityi

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

Inductioni

Induced by lipopolysaccharide (LPS) and TNFA.1 Publication

Gene expression databases

BgeeiQ14164.
CleanExiHS_IKBKE.
ExpressionAtlasiQ14164. baseline and differential.
GenevisibleiQ14164. HS.

Organism-specific databases

HPAiCAB025983.
HPA015788.

Interactioni

Subunit structurei

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. Interacts with TRIM6 (via SPRY box) (PubMed:24882218). Interacts with unanchored K48-linked polyubiquitin chains; this leads to IKBKE activation (PubMed:24882218).14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
K7Y1A22EBI-307369,EBI-8788634From a different organism.
P279582EBI-307369,EBI-6919131From a different organism.
APPBP2Q926244EBI-307369,EBI-743771
CDC37Q165433EBI-307369,EBI-295634
DDX3XO005714EBI-307369,EBI-353779
HSP90AB1P082382EBI-307369,EBI-352572
IRF3Q146532EBI-307369,EBI-2650369
MAVSQ7Z4344EBI-307369,EBI-995373
TANKQ928444EBI-307369,EBI-356349
TBK1Q9UHD22EBI-307369,EBI-356402
TBKBP1A7MCY64EBI-307369,EBI-359969
VP35Q051273EBI-307369,EBI-6148294From a different organism.

Protein-protein interaction databases

BioGridi115000. 69 interactions.
DIPiDIP-27530N.
IntActiQ14164. 40 interactions.
MINTiMINT-1132084.
STRINGi9606.ENSP00000356087.

Structurei

3D structure databases

ProteinModelPortaliQ14164.
SMRiQ14164. Positions 2-621.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 315307Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni383 – 647265Interaction with DDX3XAdd
BLAST
Regioni436 – 45722Leucine-zipperAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122961.
HOGENOMiHOG000220867.
HOVERGENiHBG008494.
InParanoidiQ14164.
KOiK07211.
OMAiCCLDKMY.
OrthoDBiEOG7Z95KH.
PhylomeDBiQ14164.
TreeFamiTF324269.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14164-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQSTANYLWH TDDLLGQGAT ASVYKARNKK SGELVAVKVF NTTSYLRPRE
60 70 80 90 100
VQVREFEVLR KLNHQNIVKL FAVEETGGSR QKVLVMEYCS SGSLLSVLES
110 120 130 140 150
PENAFGLPED EFLVVLRCVV AGMNHLRENG IVHRDIKPGN IMRLVGEEGQ
160 170 180 190 200
SIYKLTDFGA ARELDDDEKF VSVYGTEEYL HPDMYERAVL RKPQQKAFGV
210 220 230 240 250
TVDLWSIGVT LYHAATGSLP FIPFGGPRRN KEIMYRITTE KPAGAIAGAQ
260 270 280 290 300
RRENGPLEWS YTLPITCQLS LGLQSQLVPI LANILEVEQA KCWGFDQFFA
310 320 330 340 350
ETSDILQRVV VHVFSLSQAV LHHIYIHAHN TIAIFQEAVH KQTSVAPRHQ
360 370 380 390 400
EYLFEGHLCV LEPSVSAQHI AHTTASSPLT LFSTAIPKGL AFRDPALDVP
410 420 430 440 450
KFVPKVDLQA DYNTAKGVLG AGYQALRLAR ALLDGQELMF RGLHWVMEVL
460 470 480 490 500
QATCRRTLEV ARTSLLYLSS SLGTERFSSV AGTPEIQELK AAAELRSRLR
510 520 530 540 550
TLAEVLSRCS QNITETQESL SSLNRELVKS RDQVHEDRSI QQIQCCLDKM
560 570 580 590 600
NFIYKQFKKS RMRPGLGYNE EQIHKLDKVN FSHLAKRLLQ VFQEECVQKY
610 620 630 640 650
QASLVTHGKR MRVVHETRNH LRLVGCSVAA CNTEAQGVQE SLSKLLEELS
660 670 680 690 700
HQLLQDRAKG AQASPPPIAP YPSPTRKDLL LHMQELCEGM KLLASDLLDN
710
NRIIERLNRV PAPPDV
Length:716
Mass (Da):80,462
Last modified:November 1, 1996 - v1
Checksum:i3E5FBE5840734D81
GO
Isoform 2 (identifier: Q14164-2) [UniParc]FASTAAdd to basket

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

Show »
Length:631
Mass (Da):70,816
Checksum:i1E6CC6C29C88897D
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871R → Q in AAI05925 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti128 – 1281E → K.1 Publication
Corresponds to variant rs41296028 [ dbSNP | Ensembl ].
VAR_038816
Natural varianti371 – 3711A → T.2 Publications
Corresponds to variant rs17021877 [ dbSNP | Ensembl ].
VAR_038817
Natural varianti483 – 4831T → M.1 Publication
Corresponds to variant rs52817862 [ dbSNP | Ensembl ].
VAR_040571
Natural varianti515 – 5151E → D.1 Publication
Corresponds to variant rs41299015 [ dbSNP | Ensembl ].
VAR_038818
Natural varianti543 – 5431I → M.1 Publication
Corresponds to variant rs41299037 [ dbSNP | Ensembl ].
VAR_038819
Natural varianti602 – 6021A → V.2 Publications
Corresponds to variant rs12059562 [ dbSNP | Ensembl ].
VAR_038820
Natural varianti660 – 6601G → E.1 Publication
Corresponds to variant rs55822317 [ dbSNP | Ensembl ].
VAR_040572
Natural varianti713 – 7131P → L.2 Publications
Corresponds to variant rs3748022 [ dbSNP | Ensembl ].
VAR_019989

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8585Missing in isoform 2. 1 PublicationVSP_044305Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30996.1. [Q14164-1]
CCDS53464.1. [Q14164-2]
RefSeqiNP_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]
UniGeneiHs.321045.

Genome annotation databases

EnsembliENST00000581977; ENSP00000464030; ENSG00000263528.
ENST00000584998; ENSP00000462396; ENSG00000263528. [Q14164-2]
GeneIDi9641.
KEGGihsa:9641.
UCSCiuc001hdz.2. human. [Q14164-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30996.1. [Q14164-1]
CCDS53464.1. [Q14164-2]
RefSeqiNP_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]
UniGeneiHs.321045.

3D structure databases

ProteinModelPortaliQ14164.
SMRiQ14164. Positions 2-621.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115000. 69 interactions.
DIPiDIP-27530N.
IntActiQ14164. 40 interactions.
MINTiMINT-1132084.
STRINGi9606.ENSP00000356087.

Chemistry

BindingDBiQ14164.
ChEMBLiCHEMBL3038486.
GuidetoPHARMACOLOGYi2040.

PTM databases

PhosphoSiteiQ14164.

Polymorphism and mutation databases

BioMutaiIKBKE.
DMDMi14548079.

Proteomic databases

MaxQBiQ14164.
PaxDbiQ14164.
PRIDEiQ14164.

Protocols and materials databases

DNASUi9641.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000581977; ENSP00000464030; ENSG00000263528.
ENST00000584998; ENSP00000462396; ENSG00000263528. [Q14164-2]
GeneIDi9641.
KEGGihsa:9641.
UCSCiuc001hdz.2. human. [Q14164-1]

Organism-specific databases

CTDi9641.
GeneCardsiGC01P206643.
H-InvDBHIX0116011.
HGNCiHGNC:14552. IKBKE.
HPAiCAB025983.
HPA015788.
MIMi605048. gene.
neXtProtiNX_Q14164.
PharmGKBiPA134962294.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122961.
HOGENOMiHOG000220867.
HOVERGENiHBG008494.
InParanoidiQ14164.
KOiK07211.
OMAiCCLDKMY.
OrthoDBiEOG7Z95KH.
PhylomeDBiQ14164.
TreeFamiTF324269.

Enzyme and pathway databases

BRENDAi2.7.11.10. 2681.
ReactomeiREACT_24938. TRAF6 mediated IRF7 activation.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
SABIO-RKQ14164.
SignaLinkiQ14164.

Miscellaneous databases

ChiTaRSiIKBKE. human.
GeneWikiiIKBKE.
GenomeRNAii9641.
NextBioi36191.
PROiQ14164.
SOURCEiSearch...

Gene expression databases

BgeeiQ14164.
CleanExiHS_IKBKE.
ExpressionAtlasiQ14164. baseline and differential.
GenevisibleiQ14164. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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. 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. 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. "Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKepsilon kinase-mediated antiviral response."
    Rajsbaum R., Versteeg G.A., Schmid S., Maestre A.M., Belicha-Villanueva A., Martinez-Romero C., Patel J.R., Morrison J., Pisanelli G., Miorin L., Laurent-Rolle M., Moulton H.M., Stein D.A., Fernandez-Sesma A., tenOever B.R., Garcia-Sastre A.
    Immunity 40:880-895(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TRIM6 AND POLYUBIQUITIN, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-501.
  26. "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.
    , 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.

Entry informationi

Entry nameiIKKE_HUMAN
AccessioniPrimary (citable) accession number: Q14164
Secondary accession number(s): D3DT78
, Q3B754, Q3KR43, Q5JTS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: November 1, 1996
Last modified: July 22, 2015
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.