HERC5
Description
The HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5) is a protein-coding gene located on chromosome 4.
HERC5 is a gene that encodes a protein with E3 ubiquitin-protein ligase activity. It is a member of the HERC family of ubiquitin ligases, known for their roles in protein degradation and other cellular processes. HERC5 has been shown to play a critical role in antiviral responses, specifically by mediating the ISGylation (ISG15 conjugation) of target proteins. This protein is localized to the cytoplasm and perinuclear region. The gene is located on chromosome 4 in a cluster of HERC family genes. HERC5 has also been shown to interact with other proteins, including NME2 and Cyclin E1, suggesting its involvement in multiple cellular pathways.
HERC5 is a key enzyme involved in ISG15 conjugation, acting as a major E3 ligase for this process. It plays a crucial role in the innate antiviral response, particularly in interferon-stimulated cells. HERC5 functions as part of the ISGylation machinery, targeting a broad range of proteins for ISG15 modification in a relatively non-specific manner. This modification can have various effects on target proteins, influencing their activity and stability. For example, HERC5-mediated ISGylation of IRF3, a transcription factor involved in antiviral signaling, leads to its sustained activation, enhancing the antiviral response. Additionally, HERC5 ISGylation of PTEN, a phosphatase, results in its degradation, relieving its suppression of the PI3K-AKT signaling pathway and promoting cytokine production, crucial for bacterial clearance. HERC5 also directly interferes with the function of viral proteins, such as those from Ebola virus and HIV-1, by ISGylation, hindering their activity and inhibiting viral replication. Furthermore, HERC5 modifies viral proteins like influenza A NS1 and papillomavirus L1, altering their function and reducing viral virulence. HERC5 physically associates with polyribosomes and broadly modifies newly synthesized proteins during translation. In interferon-stimulated cells, newly translated viral proteins are often primary targets of HERC5-mediated ISGylation. Importantly, HERC5 promotes the activity of parkin/PRKN, another ubiquitin E3 ligase, by suppressing its autoinhibition.
HERC5 is also known as CEB1, CEBP1.
