Interferon (IFN) Stimulated Gene product of 20kDa (ISG20) is an IFN-induced antiviral exonuclease with a strong preference for single-stranded RNA and minor activity towards single-stranded DNA []. It was also independently identified by its response to estrogen and was called HEM45 (human estrogen regulated transcript) []. ISG20 may be a major effector of innate immunity against pathogens including viruses, bacteria, and parasites. It is located in promyelocytic leukemia (PML) nuclear bodies, sites for oncogenic DNA viral transcription and replication. It may carry out its function by degrading viral RNAs as part of the IFN-regulated antiviral response [].ISG20 is a DEDDh-type DnaQ-like 3'-5' exonuclease containing three conserved sequence motifs termed ExoI, ExoII and ExoIII with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis [].
