Reviewed,
UniProtKB/Swiss-Prot Q14164 (IKKE_HUMAN)
Last modified
June 16, 2009.
Version 93.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Inhibitor of nuclear factor kappa-B kinase subunit epsilon Short name=I kappa-B kinase epsilon Short name=IkBKE Short name=IKK-epsilon Short name=IKK-E EC=2.7.11.10 Alternative name(s): Inducible I kappa-B kinase Short name=IKK-i | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| 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. |
| Sequence processing | The displayed sequence is not processed. |
| 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. |
| Catalytic activity | ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]. |
| Subunit structure | May interact with MAVS/IPS1. Interacts with AZI2. Interacts with SIKE. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I, interactions are disrupted by the interaction between IKBKE and SIKE. Ref.7 Ref.8 Ref.9 Ref.10 |
| Subcellular location | Cytoplasm Probable. |
| 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. |
| Sequence similarities | Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Contains 1 protein kinase domain. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cytoplasm |
| Coding sequence diversity | Polymorphism |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | immune response Ref.1 Non-traceable author statement. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascadeInferred from expression pattern. Source: UniProtKB protein amino acid phosphorylation Ref.2Inferred from direct assay. Source: UniProtKB |
| Cellular component | cytoplasm Non-traceable author statement. Source: UniProtKB |
| Molecular function | ATP binding Non-traceable author statement. Source: UniProtKB IkappaB kinase activityInferred from electronic annotation. Source: EC NF-kappaB-inducing kinase activity Ref.2Inferred from direct assay. Source: UniProtKB protein binding Ref.10Inferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ACLY | P53396 | 1 | EBI-307369,EBI-1042794 | |
| ATIC | P31939 | 1 | EBI-307369,EBI-1048599 | |
| CLTC | Q00610 | 1 | EBI-307369,EBI-354967 | |
| DSTYK | Q6XUX3 | 1 | EBI-307369,EBI-1049520 | |
| EPRS | P07814 | 1 | EBI-307369,EBI-355315 | |
| HYOU1 | Q9Y4L1 | 1 | EBI-307369,EBI-1054186 | |
| IMPDH2 | P12268 | 1 | EBI-307369,EBI-353389 | |
| LRPPRC | P42704 | 1 | EBI-307369,EBI-1050853 | |
| MAVS | Q7Z434 | 1 | EBI-307369,EBI-995373 | |
| MYH10 | P35580 | 1 | EBI-307369,EBI-351758 | |
| PABPC1 | P11940 | 1 | EBI-307369,EBI-81531 | |
| PDIA6 | Q15084 | 1 | EBI-307369,EBI-1043087 | |
| PLS3 | P13797 | 1 | EBI-307369,EBI-698052 | |
| PPP2R1A | P30153 | 1 | EBI-307369,EBI-302388 | |
| PSMA7 | O14818 | 1 | EBI-307369,EBI-603272 | |
| ROCK2 | O75116 | 1 | EBI-307369,EBI-366288 | |
| RUVBL2 | Q9Y230 | 1 | EBI-307369,EBI-352939 | |
| SND1 | Q7KZF4 | 1 | EBI-307369,EBI-1044112 | |
| VCP | Q5VYM0 | 1 | EBI-307369,EBI-1046421 |
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 | ||||||
| Domain | 436 – 457 | 22 | Leucine-zipper Potential | ||||||
| Nucleotide binding | 15 – 23 | 9 | ATP By similarity | ||||||
Sites | |||||||||
| Active site | 135 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 38 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 172 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Natural variant | 128 | 1 | E → K Ref.5 | VAR_038816 | |||||
| Natural variant | 371 | 1 | A → T: dbSNP rs17021877. Ref.5 Ref.11 | VAR_038817 | |||||
| Natural variant | 483 | 1 | T → M Ref.11 | VAR_040571 | |||||
| Natural variant | 515 | 1 | E → D Ref.5 | VAR_038818 | |||||
| Natural variant | 543 | 1 | I → M Ref.5 | VAR_038819 | |||||
| Natural variant | 602 | 1 | A → V: dbSNP rs12059562. Ref.5 Ref.11 | VAR_038820 | |||||
| Natural variant | 660 | 1 | G → E Ref.11 | VAR_040572 | |||||
| Natural variant | 713 | 1 | P → L: dbSNP rs3748022. Ref.5 Ref.11 | VAR_019989 | |||||
Experimental info | |||||||||
| Mutagenesis | 38 | 1 | K → A: Loss of kinase activity. 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 | ||||||
| Sequence conflict | 187 | 1 | R → Q in AAI05925. Ref.6 | ||||||
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: 10421793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 10882136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 8590280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [7] | "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: 14560022] [Abstract] Cited for: INTERACTION WITH AZI2. |
| [8] | "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: 14739303] [Abstract] Cited for: INTERACTION WITH TICAM1. |
| [9] | "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: 16281057] [Abstract] Cited for: INTERACTION WITH SIKE; IRF3; TICAM1 AND DDX58. |
| [10] | "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: 16177806] [Abstract] Cited for: INTERACTION WITH MAVS. |
| [11] | "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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371; MET-483; VAL-602; GLU-660 AND LEU-713. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| 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. BC105923 mRNA. Translation: AAI05924.1. BC105924 mRNA. Translation: AAI05925.1. | |
| IPI | IPI00029045. |
| RefSeq | NP_054721.1. |
| UniGene | Hs.321045 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP:27530N. |
| IntAct | Q14164. 343 interactions. |
PTM databases | |
| PhosphoSite | Q14164. |
Proteomic databases | |
| PRIDE | Q14164. |
Genome annotation databases | |
| Ensembl | ENSG00000143466. Homo sapiens. [Contig view] |
| GeneID | 9641. |
| KEGG | hsa:9641. |
Organism-specific databases | |
| GeneCards | GC01P204710. |
| H-InvDB | HIX0001528. HIX0001529. |
| HGNC | HGNC:14552. IKBKE. |
| HPA | HPA015788. |
| MIM | 605048. gene. |
| PharmGKB | PA134962294. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q14164. |
| HOVERGEN | Q14164. |
| OMA | Q14164. FLVVLRC. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.10. 247. |
Gene expression databases | |
| ArrayExpress | Q14164. |
| Bgee | Q14164. |
| CleanEx | HS_IKBKE. |
| GermOnline | ENSG00000143466. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view] |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 36191. |
| SOURCE | Search... |
Entry information
| Entry name | IKKE_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14164 Secondary accession number(s): Q3KR43, Q5JTS6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| 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 |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


