Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:20061386). In vitro catalyzes ‘Lys-48’-linked polyubiquitination (PubMed:20061386). Involved in endoplasmic reticulum-associated degradation (ERAD) (PubMed:22607976). Required for sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation (PubMed:23223569).