E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity by mediating ubiquitination of CGAS and STING1 (PubMed:21074459, PubMed:29426904). In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets STING1 to 'Lys-63'-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (PubMed:21074459). Also mediates monoubiquitination of CGAS, thereby promoting CGAS oligomerization and subsequent activation (PubMed:29426904). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling (By similarity). Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES (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 STING1 (PubMed:21074459). Interacts with TICAM1 (By similarity). By interferon. High susceptibility to DNA virus infection, such as lethal herpes simplex virus-1 (HSV-1) (PubMed:29426904). Cells are defective in CGAS-mediated type I interferon IFN-beta production upon HSV-1 infection (PubMed:29426904). No susceptibility to RNA virus infection, such as influenza A virus (PubMed:29426904). No visible phenotype in normal conditions (PubMed:29426904). Belongs to the TRIM/RBCC family.