ISG15:RIG-I conjugate ISG15:UBEIL/UbcH8:CEB1 ISGylation of RIG-I Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 ISG15 is a ubiquitin (Ub)-like protein which is conjugated to intracellular proteins via an isopeptide bond. Similar to ubiquitination, the conjugation of ISG15 (ISGylation) requires a three-step process, involving an E1 activating enzyme (UBE1L), an E2 conjugating enzyme (UbcM8/H8), and HERC5/Ceb1 an IFN-inducible ISG15-specific E3 ligase. ISG15 conjugation may play an important regulatory role in IFN-mediated antiviral responses. IFN induces ISG15 conjugation to RIG-I protein and lowers cellular levels of unconjugated RIG-I protein and, thus, negatively regulates RIG-I-mediated antiviral signaling. ISGylated RIG-I protein becomes subject to an irreversible biochemical process, such as proteolysis or proteasomeal degradation. Pubmed18057259 Reactome Database ID Release 43936563 Reactome, http://www.reactome.org ReactomeREACT_25191 Reviewed: Kawai, T, Akira, S, 2010-10-30