KEAP1 Antibody – Rabbit Polyclonal

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. [provided by RefSeq, Jul 2008]

KEAP1: a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Has tumor suppressor activity. Retains NRF2, BPTF and PGAM5 in the cytosol. Targets NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and of antioxidant response element-mediated detoxifying enzyme gene expression. Somatic mutations of KEAP1 or NRF2 commonly occur in solid cancers, irrespective of histological type, resulting in the constitutive transcription of cytoprotective genes. Genetic disruption of the KEAP1/CUL3 E3 ubiquitin ligase complex leads to the activation of the NF-kappaB pathway in lung cancer. Alternative activation of the cytoprotective NRF2 pathway exist in the absence of mutations in KEAP1 and HRF2: WTX, PALB2, SQSTM1, and DPP3 can competitively bind KEAP1. These proteins and others that bind KEAP1 contain an ¿ETGE¿ amino acid motif, which matches the KEAP1 interaction motif found in NRF2. Binding of these ¿ETGE¿-containing proteins can displace NRF2, freeing it to translocate to the nucleus and implement its cytoprotective transcriptional pathway. The DPP3 gene is frequently overexpressed in squamous cell lung carcinomas with high wt NRF2 activity. Its expression level significantly correlates with the response rate and progression-free survival of platinum-based first-line chemotherapy. May be a useful biomarker for predicting the chemosensitivity of patients with advanced-stage NSCLC. Broadly expressed, with highest levels in skeletal muscle. Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane.

Protein type: Motility/polarity/chemotaxis; Endoplasmic reticulum; Ubiquitin conjugating system; Transcription regulation

Chromosomal Location of Human Ortholog: 19p13.2

Cellular Component: actin filament; cell-cell adherens junction; cytoplasm; cytosol; endoplasmic reticulum; focal adhesion; microtubule organizing center; midbody; nucleoplasm

Molecular Function: protein binding; transcription factor binding; ubiquitin-protein ligase activity

Biological Process: alkanesulfonate metabolic process; cytoplasmic sequestering of transcription factor; flavonoid metabolic process; in utero embryonic development; malate metabolic process; negative regulation of transcription factor activity; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasomal ubiquitin-dependent protein catabolic process; proteasomal ubiquitin-independent protein catabolic process; protein oligomerization; protein ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process; regulation of epidermal cell differentiation; response to metal ion; selenium metabolic process; transcription, DNA-dependent