KEAP1

Kelch-like ECH-associated protein 1
File:PBB Protein KEAP1 image.jpg PDB rendering based on 1u6d.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1u6d​, 1x2j​, 1x2r​, 1zgk​, 2flu​
Identifiers
Symbols	KEAP1 ; INrf2; KIAA0132; KLHL19; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454
External IDs	Template:OMIM5 Template:MGI HomoloGene: 8184
Gene ontology Molecular function Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE KEAP1 202417 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Kelch-like ECH-associated protein 1, also known as KEAP1, is a human gene.

This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene.

Further reading

• Zhang DD (2007). "Mechanistic studies of the Nrf2-Keap1 signaling pathway". Drug Metab. Rev. 38 (4): 769–89. doi:10.1080/03602530600971974. PMID 17145701.
• Nagase T, Seki N, Tanaka A; et al. (1996). "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". DNA Res. 2 (4): 167–74, 199–210. PMID 8590280.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Itoh K, Wakabayashi N, Katoh Y; et al. (1999). "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain". Genes Dev. 13 (1): 76–86. PMID 9887101.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dhakshinamoorthy S, Jaiswal AK (2001). "Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene". Oncogene. 20 (29): 3906–17. doi:10.1038/sj.onc.1204506. PMID 11439354.
• Sekhar KR, Spitz DR, Harris S; et al. (2002). "Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase". Free Radic. Biol. Med. 32 (7): 650–62. PMID 11909699.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Velichkova M, Guttman J, Warren C; et al. (2002). "A human homologue of Drosophila kelch associates with myosin-VIIa in specialized adhesion junctions". Cell Motil. Cytoskeleton. 51 (3): 147–64. doi:10.1002/cm.10025. PMID 11921171.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Zipper LM, Mulcahy RT (2002). "The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm". J. Biol. Chem. 277 (39): 36544–52. doi:10.1074/jbc.M206530200. PMID 12145307.
• Sekhar KR, Yan XX, Freeman ML (2002). "Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2". Oncogene. 21 (44): 6829–34. doi:10.1038/sj.onc.1205905. PMID 12360409.CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bloom DA, Jaiswal AK (2004). "Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression". J. Biol. Chem. 278 (45): 44675–82. doi:10.1074/jbc.M307633200. PMID 12947090.
• Cullinan SB, Zhang D, Hannink M; et al. (2003). "Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival". Mol. Cell. Biol. 23 (20): 7198–209. PMID 14517290.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Colland F, Jacq X, Trouplin V; et al. (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMID 15231748.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kobayashi A, Kang MI, Okawa H; et al. (2004). "Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2". Mol. Cell. Biol. 24 (16): 7130–9. doi:10.1128/MCB.24.16.7130-7139.2004. PMID 15282312.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Strachan GD, Morgan KL, Otis LL; et al. (2004). "Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein". Biochemistry. 43 (38): 12113–22. doi:10.1021/bi0494166. PMID 15379550.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Li X, Zhang D, Hannink M, Beamer LJ (2005). "Crystal structure of the Kelch domain of human Keap1". J. Biol. Chem. 279 (52): 54750–8. doi:10.1074/jbc.M410073200. PMID 15475350.CS1 maint: Multiple names: authors list (link)
• Zhang DD, Lo SC, Cross JV; et al. (2004). "Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex". Mol. Cell. Biol. 24 (24): 10941–53. doi:10.1128/MCB.24.24.10941-10953.2004. PMID 15572695.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Li X, Zhang D, Hannink M, Beamer LJ (2005). "Crystallization and initial crystallographic analysis of the Kelch domain from human Keap1". Acta Crystallogr. D Biol. Crystallogr. 60 (Pt 12 Pt 2): 2346–8. doi:10.1107/S0907444904024825. PMID 15583386.CS1 maint: Multiple names: authors list (link)
• Furukawa M, Xiong Y (2005). "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase". Mol. Cell. Biol. 25 (1): 162–71. doi:10.1128/MCB.25.1.162-171.2005. PMID 15601839.
• Hosoya T, Maruyama A, Kang MI; et al. (2005). "Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells". J. Biol. Chem. 280 (29): 27244–50. doi:10.1074/jbc.M502551200. PMID 15917255.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)