E3 ubiquitin-protein ligase that catalyzes 'Lys-11'- or 'Lys-33'-linked polyubiquitin chains, with some preference for 'Lys-33' linkages (By similarity). E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Ubiquitinates SEPTIN4, DIABLO/SMAC and HTRA2 in vitro (By similarity). Modulates pulmonary inflammation by targeting SOCS2 for ubiquitination and subsequent degradation by the proteasome (PubMed:31578312). 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 SOCS2 (PubMed:31578312). Interacts (via HECT domain) with HTRA2, DIABLO/SMAC and SEPTIN4; in the cytoplasm following induction of apoptosis (PubMed:23479728). Detected in brain, testis, heart, liver, lung and kidney with very low levels in skeletal muscle and spleen. Autoubiquitinated in vitro in the presence of E2 enzyme UBE2D1/UBCH5A. Mice show significant and stepwise decreases in indicators of inflammatory injury, such as bronchoalveolar lavage fluid protein concentration and cell count, as well as decreases in pro-inflammatory cytokine release. Extended N-terminus.