Family

Kelch-like ECH-associated protein 1 (IPR030563)

Short name: KEAP1

Family relationships

Description

Kelch-like ECH-associated protein 1 (KEAP1, also known as KLHL19) is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for thiol-reactive chemopreventive compounds and oxidative stress. It targets NFE2L2/NRF2 (a transcription factor) 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 [PMID: 14585973, PMID: 15983046]. Another KEAP1 substrate, PGAM5, a Bcl-XL-interacting protein, has also been identified [PMID: 17046835].

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [PMID: 23676014], while the Kelch domain (repeats) form beta-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins [PMID: 10603472]. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins [PMID: 15544948]. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [PMID: 23135275, PMID: 14528312].

GO terms

Biological Process

GO:0016567 protein ubiquitination

Molecular Function

GO:0008134 transcription factor binding

Cellular Component

GO:0031463 Cul3-RING ubiquitin ligase complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER