FIGURE 3.

A model of ERAD system. An ERAD client that has lesion in membrane-embedded segment (ERAD_M) or in ER lumen region (ERAD_L) is recruit by Hrd3 (EBS5 in Arabidopsis) and Yos9 (EBS6/OS9 in Arabidopsis) to the membrane-anchored E3 ligase Hrd1 (AtHrd1A and AtHrd1B in Arabidopsis) complex that also contains Cue1, Ubc6 (UBC32 in Arabidopsis), Usa1 and Der1. An ERAD substrate with a folding lesion in the cytosolic domain (ERAD_C is recruited to a different ER membrane-anchored E3 ligase complex that contains Doa10 and Ubc6 (or Cue1/Ubc7). The two E3 ligase complexes share similar components on the cytosolic side of the ER membrane, including the substrate-extracting Cdc48-Ufd1-Npl4 trimeric complex and its membrane recruitment factor Ubx2 (one or more AtPUX proteins in Arabidopsis). An extracted polyubiquitinated ERAD substrate is processed by Ufd2, Ufd3, Otu1, and/or Png1 (AtPNG1 in Arabidopsis), delivered to the cytosolic proteasome with help of Dsk2 and Rad23, and eventually proteolyzed by the 26S proteasome.