Anti-DERL1

The protein encoded by this gene is a member of the derlin family. Members of this family participate in the ER-associated degradation response and retrotranslocate misfolded or unfolded proteins from the ER lumen to the cytosol for proteasomal degradation. This protein recognizes substrate in the ER and works in a complex to retrotranslocate it across the ER membrane into the cytosol. This protein may select cystic fibrosis transmembrane conductance regulator protein (CFTR) for degradation as well as unfolded proteins in Alzheimer's disease. Alternative splicing results in multiple transcript variants that encode different protein isoforms. Protein function: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins (PubMed:15215856, PubMed:33658201). Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane (PubMed:33658201). This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome (PubMed:33658201). The channel has a lateral gate within the membrane which provides direct access to membrane proteins with no need to reenter the ER lumen first (PubMed:33658201). May mediate the interaction between VCP and the misfolded protein (PubMed:15215856). Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). [The UniProt Consortium]