Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins (PubMed:11329381, PubMed:12861019, PubMed:16176924, PubMed:19269966, PubMed:19285439). May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4 (PubMed:11329381). Mediates ubiquitination of PXN/paxillin,thereby regulating cell motility and localization of PXN/paxillin (PubMed:12861019). Catalyzes ubiquitination of Salmonella type III secreted protein sopA (PubMed:16176924). Mediates the ‘Lys-63’-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N (PubMed:19269966). Mediates the ‘Lys-48’-linked polyubiquitination of STING1 at ‘Lys-150’ leading to its proteasomal degradation; the ubiquitination occurs in mitochondria after viral transfection and regulates antiviral responses (PubMed:19285439). Catalyzes ubiquitination and subsequent degradation of ATG4B, thereby inhibiting autophagy (PubMed:23093945).