Endogenous

KEAP1 INRF2 KIAA0132 KLHL19

Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) (Kelch-like protein 19)

Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) (Kelch-like protein 19)

kelch like ECH associated protein 1(KEAP1) Homo sapiens 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],

Disease:Defects in KEAP1 may be a cause of breast cancer.,Disease:Defects in KEAP1 may be involved in non small cell lung carcinomas (NSCLC) and lung adenocarcinoma.,Domain:The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5.,enzyme regulation:Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane.,Function:Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. 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. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.,PTM:Ubiquitinated and subject to proteasomal degradation.,similarity:Contains 1 BACK (BTB/Kelch associated) domain.,similarity:Contains 1 BTB (POZ) domain.,similarity:Contains 6 Kelch repeats.,subcellular location:Shuttles between cytoplasm and nucleus.,subunit:Homodimer. Interacts with the N-terminal regulatory domain of NF2L2/NRF2. Interacts with BPTF and PTMA. Interacts with CUL3. Part of a complex that contains KEAP1, CUL3 and RBX1. Interacts with PGAM5.,tissue specificity:Broadly expressed, with highest levels in skeletal muscle.,

Cytoplasm, Nucleus

Broadly expressed, with highest levels in skeletal muscle.

>>Ubiquitin mediated proteolysis ;
>>Parkinson disease ;
>>Pathways in cancer ;
>>Chemical carcinogenesis - reactive oxygen species ;
>>Hepatocellular carcinoma ;
>>Fluid shear stress and atherosclerosis