RING function is regulated by the B-Box domain, which is autoinhibitory and blocks E2 enzyme recruitment (Dickson et al., 2018). To investigate whether RING-Box variants have an impact on the ability of TRIM21 to activate NF-κB signaling in response to viral infection, we needed a system for expressing TRIM21 variants in a TRIM21 KO cell line. This evidence concerns the gene TRIM21 and viral infectious disease.