HECT and RLD domain containing E3 ubiquitin-protein ligase family member 6 (HERC6)

HECT and RLD domain containing E3 ubiquitin-protein ligase family member 6 (HERC6) is a member of the small HERC subfamily of E3 ubiquitin ligases characterized by the presence of an N-terminal RCC1-like domain (RLD) and a C-terminal HECT domain, which mediates ubiquitin transfer from E2 enzymes to specific protein substrates.[7][3][4] HERC6 plays a role in ubiquitination and is involved in the innate immune response, having been identified as an interferon-inducible E3 ligase with antiviral properties, especially in mammals; its rapid evolution, particularly in the spacer region between domains, suggests adaptation to viral pathogens.[2][3] While murine HERC6 is implicated in ISG15 conjugation (ISGylation), the human orthologue acts as a bona fide ubiquitin-protein ligase with antiviral effects, such as inhibition of primate lentiviral production.[2][7] HERC6 activity is cytosolic/nuclear and spans multiple physiological processes including protein homeostasis, immune response modulation, and potentially tumor suppression or promotion, in line with other HECT E3 ligases.[3][6][4] Specific drug interactions and biomarker data are not established, but targeted modulation or dysfunction could affect both normal cellular proteostasis and immune responses.

Other names

HERC6Probable E3 ubiquitin-protein ligase HERC6FLJ20637HECT domain and RCC1-like domain-containing protein 6HECT-type E3 ubiquitin transferase HERC6Potential ubiquitin ligase

Targeted protein degradation via ubiquitin-proteasome pathway Potential ISGylation (notably in mouse HERC6, not in human)