E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator p27Kip1. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo. Binds UBQLN1 and UBQLN2. Interacts with the 26S proteasome. Interacts with HCV core protein and targets it to degradation. Interacts with the E6 protein of the cancer- associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53/TP53 tumor-suppressor protein for ubiquitin-mediated proteolysis. Interacts with BPY2. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.