Ubiquitylation of an ERAD Substrate Occurs on Multiple Types of Amino Acids

► Promiscuity in amino acid modification allows Hrd1 to recognize numerous ER proteins ► Hrd1 required for Ub conjugation not only on lysines but also on serines/threonines ► Hrd1-mediated ubiquitin chain elongation is via conventional isopeptide linkages ► Mutation of K, S, and T residues is required to inhibit Ub and stabilize NS-1 LC