Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins (PubMed:23093945). May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4 (By similarity). Mediates ubiquitination of PXN/paxillin,thereby regulating cell motility and localization of PXN/paxillin (By similarity). 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 (By similarity). 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 (By similarity). Catalyzes ubiquitination and subsequent degradation of ATG4B, thereby inhibiting autophagy (PubMed:23093945). 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 PXN (By similarity). Interacts with JKAMP (PubMed:16166642). Interacts with STING1; the interaction of endogenous proteins is dependent on viral infection (By similarity). Predominantly located in the plasma membrane, with some localization occurring within cytoplasmic organelles. Mice are more resistant to lethal infections by group A Streptococcus due to increased autophagy (PubMed:23093945). Macrophages show increased autophagosomes and more efficient bacterial clearance (PubMed:23093945). Belongs to the RNF5 family.