Table 1.
Cytosol- and membrance-associated | Merribrane-associated | ER lumen- and membrane-associated | ||||
---|---|---|---|---|---|---|
ERAD-C | Degradation | 26S proteasome | E3 | Doa10 | ||
Retrotranslocation | Cdc48–Ufd1–Npl4–Ubx2 | E2 | Ubc6 and Ubc7–Cue1 | |||
Chaperones | Ssa1, Ydj1 and HIj1 | |||||
ERAD-M | Degradation | 26S proteasome | E3 | Hrd1–Hrd3 | ||
Retrotranslocation | Cdc48–Ufd1–Npl4–Ubx2 | E2 | Ubc7–Cue1 | |||
ERAD-L | Degradation | 26S proteasome | E3 | Hrd1–Hrd3 | Putative lectins | Yos9 and Htm1/Mnl1 |
Retrotranslocation | Cdc48–Ufd1–Npl4–Ubx2 | E2 | Ubc7–Cue1 | Chaperones | BiP (Kar2), Scj1, Jem1 and PDI | |
Putative retrotranslocon components | Der1, Sec61, Ssh1 and Usa1 | |||||
Other components | Polyubiquitination | Ufd2 | ||||
Deubiquitination | Rpn11 and Otu1 | |||||
Escort | Rad23–Dsk2 | |||||
Deglycosylation | Png1 |
Components involved in the ERAD-C, -M or -L pathways as listed by their locations. Note that the functions of Ufd2 and Rad23-Dsk2 have not been well characterized for multiple ERAD substrates, and the direct involvement of Rpn11, Otu1 and Png1 during ERAD is still being elucidated. Ubx2 and Cue1 are membrane proteins that recruit the Cdc48 complex and Ubc7 to the ER membrane, respectively. Hrd3 is a membrane protein that stabilizes Hrd1 and recognizes lumenal substrates through its lumenal domain. Usa1 is also a membrane protein that appears to help link the Hrd1 E3 ligase complex and Der1 and is a specific component of the ERAD-L pathway (52).