kelch-like ECH-associated protein 1; cytosolic inhibitor of Nrf2; INrf2; kelch-like protein 19 (KEAP1, INRF2, KIAA0132, KLHL19)

Function

• cytoplasmic anchoring of NRF2
• substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 & RBX1
• targets NFE2L2/NRF2 for ubiquitination & degradation by the proteasome, resulting in suppression of its transcriptional activity & repression of antioxidant response element- mediated detoxifying enzyme gene expression
• may also retain BPTF in the cytosol
• targets PGAM5 for ubiquitination & degradation by the proteasome
• ubiquitination & subsequent degradation of PGAM5 is inhibited by oxidative stress & sulforaphane
• ubiquitinated & subject to proteasomal degradation
• forms a ternary complex with NFE2L2 & PGAM5
• interacts with the N-terminal regulatory domain of NFE2L2/NRF2
• interacts with BPTF & PTMA
• interacts with CUL3
• part of a complex that contains KEAP1, CUL3 & RBX1

Structure

• homodimer
• the kelch repeats mediate interaction with NF2L2/NRF2, BPTF & PGAM5
• contains 1 BACK (BTB/kelch associated) domain
• contains 1 BTB/POZ domain
• contains 6 kelch repeats

Compartment

• cytoplasm, nucleus
• shuttles between cytoplasm & nucleus

Expression

• widely expressed
• highest expression in skeletal muscle

More general terms

• kelch-like protein
• phosphoprotein

Additional terms

• nuclear factor erythroid 2-related factor 2; NF-E2-related factor 2; NFE2-related factor 2; nuclear factor, erythroid derived 2, like 2; HEBP1 (NFE2L2 NRF2)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9817
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9817
• OMIM: https://mirror.omim.org/entry/606016
• UniProt: http://www.uniprot.org/uniprot/Q14145.html