Q14164 (IKKE_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 138.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 716 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. May play a special role in the immune response. Protects cells against DNA damage-induced cell death. Ref.14 Ref.15 |
| Catalytic activity | ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]. |
| Subunit structure | May interact with MAVS/IPS1. Interacts with AZI2. 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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 |
| Subcellular location | Cytoplasm. Nucleus. Nucleus › PML body. Note: Targeting to PML nuclear bodies upon DNA damage is TOPORS-dependent. Ref.14 |
| Tissue specificity | Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon. |
| Post-translational modification | Autophosphorylated and phosphorylated by IKBKB/IKKB. Ref.15 Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1. Ref.14 |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| MAVS | Q7Z434 | 2 | EBI-307369,EBI-995373 |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 716 | 716 | Inhibitor of nuclear factor kappa-B kinase subunit epsilon | PRO_0000086017 | |||||
Regions | |||||||||
| Domain | 9 – 315 | 307 | Protein kinase | ||||||
| Nucleotide binding | 15 – 23 | 9 | ATP By similarity | ||||||
| Region | 436 – 457 | 22 | Leucine-zipper | ||||||
Sites | |||||||||
| Active site | 135 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 38 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 172 | 1 | Phosphoserine; by IKKB | ||||||
| Modified residue | 664 | 1 | Phosphoserine Ref.13 | ||||||
| Cross-link | 231 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.14 | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 85 | 85 | Missing in isoform 2. | VSP_044305 | |||||
| Natural variant | 128 | 1 | E → K. Ref.4 Corresponds to variant rs41296028 [ dbSNP | Ensembl ]. | VAR_038816 | |||||
| Natural variant | 371 | 1 | A → T. Ref.4 Ref.16 Corresponds to variant rs17021877 [ dbSNP | Ensembl ]. | VAR_038817 | |||||
| Natural variant | 483 | 1 | T → M. Ref.16 Corresponds to variant rs52817862 [ dbSNP | Ensembl ]. | VAR_040571 | |||||
| Natural variant | 515 | 1 | E → D. Ref.4 Corresponds to variant rs41299015 [ dbSNP | Ensembl ]. | VAR_038818 | |||||
| Natural variant | 543 | 1 | I → M. Ref.4 Corresponds to variant rs41299037 [ dbSNP | Ensembl ]. | VAR_038819 | |||||
| Natural variant | 602 | 1 | A → V. Ref.4 Ref.16 Corresponds to variant rs12059562 [ dbSNP | Ensembl ]. | VAR_038820 | |||||
| Natural variant | 660 | 1 | G → E. Ref.16 Corresponds to variant rs55822317 [ dbSNP | Ensembl ]. | VAR_040572 | |||||
| Natural variant | 713 | 1 | P → L. Ref.4 Ref.16 Corresponds to variant rs3748022 [ dbSNP | Ensembl ]. | VAR_019989 | |||||
Experimental info | |||||||||
| Mutagenesis | 38 | 1 | K → A: Loss of kinase activity and loss of nuclear import. Ref.1 | ||||||
| Mutagenesis | 168 | 1 | E → A: Slight decrease of kinase activity. Ref.1 | ||||||
| Mutagenesis | 172 | 1 | S → A: Loss of autophosphorylation and of kinase activity. Ref.1 | ||||||
| Mutagenesis | 172 | 1 | S → E: Decrease in kinase activity. Ref.1 | ||||||
| Mutagenesis | 231 | 1 | K → R: Loss of sumoylation and loss of targeting to nuclear bodies. Ref.14 | ||||||
| Sequence conflict | 187 | 1 | R → Q in AAI05925. Ref.7 | ||||||
Sequences
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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. 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. 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] | "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. |
| [13] | "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, MASS SPECTROMETRY. |
| [14] | "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. |
| [15] | "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. |
| [16] | "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. 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. |
| IPI | IPI00029045. |
| RefSeq | NP_001180250.1. NM_001193321.1. NP_001180251.1. NM_001193322.1. NP_054721.1. NM_014002.3. |
| UniGene | Hs.321045. |
3D structure databases | |
| ProteinModelPortal | Q14164. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-27530N. |
| IntAct | Q14164. 9 interactions. |
| MINT | MINT-1132084. |
| STRING | 9606.ENSP00000356087. |
PTM databases | |
| PhosphoSite | Q14164. |
Polymorphism databases | |
| DMDM | 14548079. |
Proteomic databases | |
| PaxDb | Q14164. |
| PRIDE | Q14164. |
Protocols and materials databases | |
| DNASU | 9641. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000367120; ENSP00000356087; ENSG00000143466. ENST00000537984; ENSP00000444529; ENSG00000143466. ENST00000581977; ENSP00000464030; ENSG00000263528. ENST00000584998; ENSP00000462396; ENSG00000263528. |
| GeneID | 9641. |
| KEGG | hsa:9641. |
| UCSC | uc001hdz.2. human. |
Organism-specific databases | |
| CTD | 9641. |
| GeneCards | GC01P206643. |
| H-InvDB | HIX0116011. |
| HGNC | HGNC:14552. IKBKE. |
| HPA | CAB025983. HPA015788. |
| MIM | 605048. gene. |
| neXtProt | NX_Q14164. |
| PharmGKB | PA134962294. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0515. |
| HOGENOM | HOG000220867. |
| HOVERGEN | HBG008494. |
| InParanoid | Q14164. |
| KO | K07211. |
| OMA | HIYIHAH. |
| OrthoDB | EOG4S4PFW. |
| PhylomeDB | Q14164. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.10. 2681. |
| Reactome | REACT_6900. Immune System. |
| SignaLink | Q14164. |
Gene expression databases | |
| ArrayExpress | Q14164. |
| Bgee | Q14164. |
| CleanEx | HS_IKBKE. |
| Genevestigator | Q14164. |
| GermOnline | ENSG00000143466. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. [Graphical view] |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | Q14164. |
| ChEMBL | CHEMBL3529. |
| ChiTaRS | IKBKE. human. |
| GenomeRNAi | 9641. |
| NextBio | 36191. |
| SOURCE | Search... |
Entry information
| Entry name | IKKE_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14164 Secondary accession number(s): D3DT78 Q5JTS6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
