E3 ISG15--protein ligase HERC5 (HERC5)

Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machines that recognizes target proteins in a broad and comparatively non-specific manner.

Catalyzes ISGylation of IRF3 which leads to sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 that attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets.