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Surprisingly, despite the structural diversity and sheer quantity of potential ERAD substrates (estimated to be up to one-third of all eukaryotic proteins (Huh et al., 2003)), only a handful of E2s and E3s have been implicated in ERAD (Christianson and Ye 2014), suggesting that the ERAD ubiquitylation machinery operates more opportunistically and with less substrate stringency than the cytoplasmic quality control system
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