E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as DDX58/RIG-I, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729, PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of DDX58/RIG-I at 'Lys-181', leading to DDX58/RIG-I degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525). 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 UBE2D1 (PubMed:27411375). Interacts with VCP/p97; leading to recruit RNF125 to DDX58/RIG-I and promote ubiquitination of DDX58/RIG-I (PubMed:26471729). Shows a reticular staining pattern within the cell and is probably expressed at other intracellular membranes in addition to the Golgi membrane. Not detected at the plasma membrane. Predominantly expressed in lymphoid tissues, including bone marrow, spleen and thymus. Also weakly expressed in other tissues. Predominant in the CD4(+) and CD8(+) T-cells, suggesting that it is preferentially confined to T-cells. Down-regulated by miR-15b (PubMed:26202983). Down-regulated in BRAFi resistant melanomas, leading to increased levels of JAK1 and possibly promoting BRAFi resistance. The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin) (PubMed:27411375). Autoubiquitinated, leading to its subsequent proteasomal degradation. The disease is caused by variants affecting the gene represented in this entry.