HERC5 Human
Description
Product Specs
Belonging to the HERC family of ubiquitin ligases and situated within a cluster of HERC genes on chromosome 4, HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5) plays a crucial role in cellular processes. Characterized by its HECT domain and five RCC1 repeats, this protein resides in the cytoplasm and perinuclear region. HERC5 functions as an interferon (INF)-induced E3 protein ligase, facilitating the ISGylation of specific protein targets. Notably, it demonstrates antiviral properties against HIV-1, influenza A virus, and human papillomavirus. Its role as a major E3 ligase for ISG15 conjugation underscores its significance in the immune response. Furthermore, HERC5 positively regulates the innate antiviral response within cells stimulated by INF. The protein is upregulated in endothelial cells by pro-inflammatory cytokines. Interestingly, HERC5 exhibits a physical association with polyribosomes, suggesting its involvement in cotranslationally modifying newly synthesized proteins.
Product Science Overview
HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 5, also known as HERC5, is a member of the HERC family of ubiquitin ligases. This family of proteins is characterized by the presence of a HECT (Homologous to E6AP C-Terminus) domain and RCC1-like domains (RLDs). HERC5 plays a crucial role in the ubiquitination process, which is essential for regulating protein function and degradation within cells.
HERC5 contains a HECT domain at its C-terminus, which is responsible for its enzymatic activity. The HECT domain is divided into two lobes: the N-terminal lobe (N-lobe) that binds to the E2 ubiquitin-conjugating enzyme, and the C-terminal lobe (C-lobe) that carries the catalytic cysteine necessary for ubiquitin transfer . The flexible hinge region connecting these lobes allows the C-lobe to move and facilitate the transfer of ubiquitin from the E2 enzyme to the substrate protein .
In addition to the HECT domain, HERC5 contains multiple RCC1-like domains (RLDs) that are involved in protein-protein interactions and substrate recognition. These domains contribute to the specificity and selectivity of HERC5 in targeting substrates for ubiquitination .
Ubiquitination is a post-translational modification that involves the covalent attachment of ubiquitin to target proteins. This process is critical for regulating various cellular processes, including protein degradation, signal transduction, and immune responses . HERC5, as an E3 ubiquitin ligase, plays a pivotal role in this process by recognizing specific substrates and facilitating their ubiquitination.
HERC5 is particularly important in the context of the immune response. It is upregulated in response to pro-inflammatory cytokines and has been shown to target viral proteins for degradation, thereby contributing to the antiviral defense mechanism of the host cell .
The activity and substrate specificity of HERC5 are tightly regulated through various mechanisms, including protein-protein interactions, post-translational modifications, and the binding of calcium ions . Dysregulation of HERC5 activity has been implicated in several diseases, including cancer and neurological disorders . Understanding the regulatory mechanisms of HERC5 is crucial for developing therapeutic strategies aimed at modulating its activity in disease-related pathways.
