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

General

kelch-like protein phosphoprotein

Properties

SIZE: entity length = 624 aa MW = 70 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: BTB domain {77-149} MOTIF: Zinc finger NAME: Zinc finger EFFECTOR-BOUND: Zn+2 BACK {184-286} Ser phosphorylation site {S293} Ser phosphorylation site {S295} nuclear export signal {301-310} kelch repeat {327-372} kelch repeat {373-423} kelch repeat {424-470} kelch repeat {471-517} kelch repeat {518-564} kelch repeat {565-611}

Database Correlations

OMIM 606016 UniProt Q14145 PFAM correlations Entrez Gene 9817 Kegg hsa:9817

References

UniProt :accession Q14145