HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 (HERC1)

HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 (HERC1) is a very large E3 ubiquitin ligase that belongs to the HERC protein family, characterized by the presence of a carboxyl-terminal HECT ubiquitin ligase domain and multiple RCC1-like (RLD) domains[1][2][4][5][6]. HERC1 functions primarily as a ubiquitin ligase, mediating the polyubiquitination and subsequent proteasomal degradation of diverse substrate proteins, including key signaling regulators such as C-RAF and TSC2[1][2][6]. It plays essential roles in processes such as protein turnover, DNA damage repair, cell proliferation, intracellular vesicle trafficking, and neurodevelopment[1][2][3][6]. Dysfunction or mutation of HERC1 is associated with neurodevelopmental syndromes (including intellectual disability and macrocephaly) and is implicated in cancer development, due in part to loss of regulation over signaling pathways like mTORC1 and ERK/MAPK[1][2][6]. HERC1 mutations disrupt cellular homeostasis, autophagy, and growth regulation and have been linked to both inherited neurological syndromes and malignancy risk[1][2][3][6].

Other names

Probable E3 ubiquitin-protein ligase HERC1HERC1p532p619HECT domain and RCC1-like domain-containing protein 1HECT-type E3 ubiquitin transferase HERC1MDFPMRguanine nucleotide exchange factor p532

Drugs targeting HERC1 would typically act through modulation of E3 ubiquitin ligase activity, affecting substrate protein stability and degradation. Possible modulation of downstream signaling (e.g., mTORC1, ERK/MAPK pathway).