E3 ubiquitin ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process acts on misfolded proteins as well as in the regulated degradation of correctly folded proteins (By similarity). Protein modification; protein ubiquitination. Also concentrates at the perinuclear endoplasmic reticulum. The C-terminal transmembrane domain is indispensable for the localization to the ER.