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]

Function: 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.13

Enzyme regulation: Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. Sulforaphane also inhibits ubiquitination of NFE2L2/NRF2. Ref.10 Ref.13

Pathway: Protein modification; protein ubiquitination.

Subunit structure: Homodimer. Forms a ternary complex with NFE2L2 and PGAM5. Interacts with the N-terminal regulatory domain of NFE2L2/NRF2. Interacts with BPTF and PTMA. Interacts with CUL3. Part of a complex that contains KEAP1, CUL3 and RBX1. Interacts with NFE2L1. Interacts indirectly with ENC1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.19

Subcellular location: Cytoplasm. Nucleus. Note: Shuttles between cytoplasm and nucleus. Ref.7 Ref.8 Ref.11 Ref.15

Tissue specificity: Broadly expressed, with highest levels in skeletal muscle. Ref.8

Domain: The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5. Ref.13

Post-translational modification: Ubiquitinated by the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and is subject to proteasomal-independent degradation. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress. Ref.9 Ref.10

Sequence similarities: Contains 1 BACK (BTB/Kelch associated) domain.Contains 1 BTB (POZ) domain.Contains 6 Kelch repeats.

Sequence caution: The sequence BAA09481.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.