RNF125 acts as an E3-ubiquitin ligase that conjugates with RIG-I (DDX58), MDA5 (IFIH1) and IPS-1 (MAVS) and mediate their proteosomal degradation. UbcH1, UbcH5a, UbcH5b, and UbcH5c function as an E2 enzyme and conjugate ubiquitin to RNF125 and DDX58 via K48. Among these enzymes UbcH5c is the major E2 enzyme showing enhanced ubiquitin conjugation to DDX58. RNF125 mediated ubiquitination of RIG-I, MDA5 and MAVS (IPS-1) inhibits DDX58/IFIH1 signaling by shunting these proteins toward proteasomal degradation.
ubiquitin-protein transferase activity of RNF125:E2 enzyme (UBE2K, UbcH5a-c):K48-polyubiquitin [cytosol]
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