E3 ubiquitin ligase complex for substrates with misfolded cytosolic domains

  • only other ERAD-active E3 in yeast besides Hrd1p
  • Has broad substrate specificity, encompassing membrane proteins, as well as soluble cytosolic and nuclear proteins and even exhibits some functional overlap with Hrd1p (Swanson, 2001; Genes Dev)
  • Doa10p surveys potential substrates without stably associated adaptors, the only other members of the core Doa10p complex are the E2 ubiquitin conjugating enzymes Ubc6p and Ubc7p (along with Cue1p, the membrane anchor for Ubc7p) (Ravid et al., 2006; EMBO J)
  • may directly bind improperly exposed hydrophobic surfaces on the cytosolic surface of the ER membrane