Fig. 2
From: Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder
Location and functional consequences of the identified NRF2 variants. a Location of the mutations in the NFE2L2 gene. All NFE2L2 mutations that have been identified are heterozygous de novo missense mutations in exon 2. b Linear representation of the NRF2 polypeptide showing the detailed position of the mutations in the Neh2 domain. All mutations are located either in the DLG or the ETGE motif. These motifs are essential for binding two molecules KEAP1 in unstressed conditions leading to rapid degradation of NRF2. The mutations inhibit the binding of KEAP1 thereby increasing NRF2 levels in the absence of stress and consecutive chronic activation of stress response genes
