Figure 1. Protein domains of Keap1 and Nrf2.

Keap1 consists of five domains: NTR, BTB, IVR, Kelch region (also known as DGR), and CTR. The BTB domain can facilitate Keap1 forming a dimer and interacting with Cul3. The DGR and CTR are also known as the DC domain, which is the Keap1- and Nrf2-binding region. Nrf2 contains six Nrf2-ECH homology (Neh) domains. Neh1 contains a CNC-type basic leucine zipper DNA-binding motif, which is required for the heterodimerization of Nrf2 and proteins of the small Maf family. The Neh2 contains DLG and ETGE motifs. They bind to the Kelch domain of Keap1 with different affinities, regulating the activity of Nrf2. The Neh3 domain helps stabilize the Nrf2 protein. Neh4 and Neh5 are related to transcriptional activity. Neh6 contains a serine-rich conserved region that inhibits Nrf2 independent of Keap1.