Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins (, ). Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane . This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome . 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 . May mediate the interaction between VCP and the misfolded protein . 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 . By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway .
(Microbial infection) In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein.
Subcellular locations: Endoplasmic reticulum membrane
Ubiquitous.