HECT Domain And RCC1 Like Domain Protein 5 (HERC5)

HERC5 is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The gene lies in a cluster of HERC family genes on chromosome 4.Immunoprecipitation and immunoblot analysis confirmed that HERC5 specifically copurified with ISG15. RT-PCR analysis detected upregulated HERC5 expression after IFNB treatment. Suppression of HERC5 using small interfering RNA showed that HERC5 was required for the ISG15 conjugation system (ISGylation) following IFNB treatment.