HECT and RCC1-like domain-containing protein 5 (HERC5)

HECT and RCC1-like domain-containing protein 5 (HERC5) is an interferon-induced E3 protein ligase characterized by an N-terminal RCC1-like domain (RLD) and a C-terminal HECT (homologous to E6-AP carboxyl terminus) domain[1][2][3]. As a member of the HERC family, HERC5 localizes to the cytoplasm and perinuclear region, and is a critical component of the ISG15 conjugation (ISGylation) system, particularly during innate immune responses to viral infection[1][2][3][4]. HERC5 facilitates the covalent attachment of the ubiquitin-like modifier ISG15 to specific substrate proteins, regulating their stability or function. This activity is dependent on a conserved catalytic cysteine residue in its HECT domain. HERC5 expression is upregulated by type I interferons and pro-inflammatory cytokines, especially in endothelial and other immune-reactive cells. While HERC5 may play roles in infection and inflammation-related pathologies, it is not currently a direct therapeutic target for approved drugs, but is of significant interest in antiviral and immune modulation research[1][2][3][5].

Other names

E3 ISG15--protein ligase HERC5Cyclin-E-binding protein 1CEB1CEBP1HECT domain and RCC1-like domain-containing protein 5Probable E3 ubiquitin-protein ligase HERC5

Conjugation of ISG15 to target proteins via E3 ligase function (for ISGylation) and conjugation of ubiquitin to target proteins (as a HECT-type E3 ligase).