RNF185 destabilizes specific membrane proteins that span all ERAD branches
Chino, H.; Ruiz, I. M.; Corbo, J. H.; Paulo, J. A.; Shao, S.
Show abstract
The endoplasmic reticulum (ER) is the primary site of eukaryotic membrane protein synthesis and quality control, which largely relies on ER-associated degradation (ERAD) to eliminate aberrant nascent proteins. In yeast, two ubiquitin ligases target proteins for ERAD based on aberrancies in substrate transmembrane (ERAD-M), lumenal (ERAD-L), or cytosolic (ERAD-C) domains. How an expanded repertoire of mammalian ERAD factors selects substrates across these classifications is unclear. Here, we show that the human ER-resident RNF185 ubiquitin ligase complex destabilizes a small but specific set of membrane proteins that span all three ERAD branches. Comparisons of three single-pass membrane proteins destabilized by RNF185 identify ERAD-M features in misoriented CHST10, ERAD-C features in unassembled SRPRB, and N-linked glycosylation-dependent ERAD-L features in ATP1B2. Our findings identify RNF185-destabilized membrane proteins with distinct aberrancies that collectively encompass all canonical ERAD substrate classifications and unexpectedly diverse quality control defects.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Molecular Insights into the Regulation of GNPTAB by TMEM251 95%
- Nucleophagy is promoted by two autophagy receptors and inhibited by chromatin-nuclear envelope tethering in fission yeast 95%
- SEL1L-HRD1 ER-Associated Degradation Facilitates Prohormone Convertase 2 Maturation and Glucagon Production in Islet α Cells 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion function for retrotranslocation of ER multi-spanning membrane substrates 95%
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement 94%
- Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.