E2-dependent E3 ubiquitin-protein ligase that functions as a RIG-I/DDX58 coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed:19017631, PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a ubiquitin-independent parallel mechanism, which consists in bridging RIG-I/DDX58 filaments forming on longer viral RNAs, further activates the RIG-I signaling pathway (PubMed:31006531). This second mechanism that synergizes with the ubiquitin-dependent one would thereby allow an RNA length-dependent regulation of the RIG-I signaling pathway (Probable). Associated with the E2 ligase UBE2N, also constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may also activate the RIG-I signaling pathway (PubMed:28469175, PubMed:31006531). 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. Homodimer (PubMed:31006531). Interacts (homodimer) with DDX58 (double-stranded RNA-bound oligomeric form); involved in both DDX58 ubiquitination, oligomerization into filaments associated with viral RNAs and the bridging of these filaments (PubMed:19017631, PubMed:19484123, PubMed:23950712, PubMed:28469175, PubMed:31006531). Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated ubiquitination of DDX58 and activation of the RIG-I signaling pathway (PubMed:28469175). Interacts with PCBP2 (PubMed:19881509). Expressed in skeletal muscle, spleen, kidney, placenta, prostate, stomach, thyroid and tongue. Also weakly expressed in heart, thymus, liver and lung. The B30.2/SPRY domain mediates the interaction with the substrate RIG-I/DDX58. The coiled-coil domains mediate homodimerization and the bridging of viral RNA-associated RIG-I/DDX58 filaments. (Microbial infection) Cleaved and inactivated by hepatitis C virus NS3/NS4A. Ring finger protein 135 (RNF135)