• Individual E3s can survey overlapping but distinct ranges of substrates with diverse topologies: with misfolded domains in the ER lumen (ERAD-L), membrane (ERAD-M) or cytosolic (ERAD-C) compartments (Carvalho et al., 2006; Cell)
  • E3s in yeast: Hrd1p, Doa10p
  • E3s in metazoans: HRD1, gp78, RMA1 (RNF5), TRC8, TEB4 (MARCH IV) (Kostova, Tsai & Weissman, 2007; Semin Cell Dev. Biol)
  • Adaptors control E3 substrate interactions: adapters are the peripheral components of the E3 complex that impart the rich substrate repertoire and stringent specificity of ERAD (e.g. Hrd3p in yeast, SEL1L in mammals)