Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. Ubiquitinates STUB1-associated HSP90AB1 in vitro. Lacks inherent specificity for any particular lysine residue of ubiquitin. Essential for viral activation of IRF3. Mediates polyubiquitination of CYP3A4.Liou YC, et al. (2002) Proc Natl Acad Sci U S A 99, 1335-40 Tagliati F, et al. (2006) Endocrinology 147, 3530-8Zou Y, et al. (2004) J Biol Chem 279, 27790-8