HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4)

HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4) is a member of the HECT-type E3 ligase family, characterized by the presence of a HECT ubiquitin ligase domain and one or more RCC1-like (RLD) domains[4][5]. HERC4 catalyzes the transfer of ubiquitin from an E2 enzyme to specific substrate proteins, regulating their stability, interactions, and cellular localization as part of the ubiquitin-proteasome system[1][5]. The RLD domains are believed to modulate its substrate specificity and possibly function in G-protein regulation[5]. HERC4 plays roles in protein trafficking, cellular structure distribution, and is essential for sperm maturation and fertility[2][5]. Recent studies have implicated HERC4 in the targeted degradation of the immune regulator STING, making it relevant to immune signaling and suggesting druggability in immunomodulation or cancer[3]. Altered HERC4 expression has been observed in several cancers, including breast, liver, and lung tumors, and it is being investigated both as a potential therapeutic target (e.g., for small-molecule degraders) and a biomarker in oncology and reproductive health[3][4][5].

Other names

Probable E3 ubiquitin-protein ligase HERC4HECT domain and RCC1-like domain-containing protein 4HECT-type E3 ubiquitin transferase HERC4KIAA1593DKFZP564G092Q5GLZ8 (UniProt accession)HERC4_HUMAN

Targeted protein degradation via ubiquitination (E3 ligase activity); Small molecule-induced degradation (e.g., STING degradation through AK59–HERC4 axis)