FIG. 9.

Organization of Nrf2. The Nrf2 protein comprises six domains (Neh1–6) with different functionalities. Neh2: Keap1 binding site; Neh4 and 5: transactivation (TA) site harbors the nuclear export signal (NES) with the redox-sensitive C183, and is required for binding of Nrf2 to its responsive element and interaction with the coactivator CBP/p300; Neh6: linker, site responsible for Keap1-independent nuclear degradation under oxidative stress (324); Neh1: contains the Cap ‘n’ Collar region (CNC), the redox-insensitive NES, the nuclear localization signal (NLS) with the redox-sensitive C506, and the bZIP motif; Neh3: the C-terminal domain contains Y568 and is required for transactivation (345). S40 is the phosphorylation site for PKCδ and ι; Y568, the phosphorylation site for Fyn. Arrows mark putative sites for casein kinases. Two novel NLSs spanning amino acids 42–53 and 587–593 identified in the mouse sequences are not included for sake of clarity (478). For numbering of different species see ref. (176).