HECT and RLD domain containing E3 ubiquitin protein ligase 3 (HERC3)

HECT and RLD domain containing E3 ubiquitin protein ligase 3 (HERC3) is a member of the HERC family of E3 ubiquitin ligases that catalyze the transfer of ubiquitin from E2 enzymes to substrate proteins, using a HECT domain for catalytic activity and an RCC1-like domain for substrate interaction[1][2][4][5][9]. HERC3 regulates protein turnover, and is located primarily in the cytosol and vesicular structures. It interacts with substrates such as EIF5A2 and mediates their degradation via K27- and K48-linked ubiquitination, affecting pathways such as EMT, cell migration, and immune system functions[2][4]. HERC3 acts as a tumor suppressor in colorectal cancer, where lower expression is linked to poor prognosis and increased tumor aggressiveness[2]. Mutations or deregulated expression of HERC3 have been associated with gastric adenocarcinoma, atypical follicular adenoma, and other diseases[1][4]. There are no approved drugs or inhibitors that modulate HERC3 directly, but its role in cancer biology points to future therapeutic relevance.

Other names

HECT domain and RCC1-like domain-containing protein 3HECT-type E3 ubiquitin transferase HERC3KIAA0032HERC3 (official gene symbol)

null (no clinical drugs known to act directly on HERC3)