Anti-Keap1 Antibody Picoband® Fluoro488 Conjugated

KEAP1 (KELCH-LIKE ECH-ASSOCIATED PROTEIN 1), is a protein that in humans is encoded by the Keap1 gene. The KIAA0132 gene is mapped on 19p13.2. Keap1 contains a central BTB/POZ domain and a C-terminal double glycine repeat (DGR), or Kelch, module. Keap1 has been shown to interact with Nrf2, a master regulator of the antioxidant response, which is important for the amelioration of oxidative stress. In the presence of the electrophilic agent diethylmalate, Nrf2 activity is released from Keap1 and Nrf2 translocate to the nucleus. Under quiescent conditions, Nrf2 is anchored in the cytoplasm through binding to Keap1, which, in turn, facilitates the ubiquitination and subsequent proteolysis of Nrf2. Because Nrf2 activation leads to a coordinated antioxidant and anti-inflammatory response, and Keap1 represses Nrf2 activation, Keap1 has become a very attractive drug target.

E.coli-derived human Keap1 recombinant protein (Position: E25-E205) . Human Keap1 shares 96.7% and 97.2% amino acid (aa) sequence identity with mouse and rat Keap1, respectively.

Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. .

1. Cullinan, Sara B; Zhang Donna, Hannink Mark, Arvisais Edward, Kaufman Randal J, Diehl J Alan (Oct. 2003) . Nrf2 is a PERK substrate and effector of PERK-dependent cell survival. 2. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., Yamamoto, M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13: 76-86, 1999. 3. Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., Nomura, N. 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: 167-174, 1995.