E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-29'- and 'Lys-48'-linked polyubiquitin chains (By similarity). Accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Associates with the proteasome and promotes elongation of ubiquitin chains on substrates bound to the 26S proteasome (By similarity). Also catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response to proteotoxic stress, impairing the ability of the proteasome to bind and degrade ubiquitin-conjugated proteins (By similarity). Acts as a negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-linked ubiquitination of PIK3C3/VPS34, promoting its degradation (By similarity). Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference for 'Lys-48' linkages (By similarity). Acts as a negative regulator of type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to their degradation by the proteasome (PubMed:21167755). Catalyzes ubiquitination and degradation of CAND2 (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with 26S proteasomes. Interacts (via the HECT domain) with UBE2D1 and, less efficiently, with UBE2L3. Autoubiquitinated; promoting its own degradation. Belongs to the UBE3C family.