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Desumoylating Isopeptidase 1 (DESI1) is a protein encoded by the DESI1 gene in humans. This enzyme plays a crucial role in the post-translational modification of proteins through the process of desumoylation, which involves the removal of Small Ubiquitin-like Modifier (SUMO) proteins from substrate proteins. Desumoylation is essential for the regulation of various cellular processes, including transcription, DNA repair, and signal transduction.
The DESI1 gene is located on chromosome 22 and encodes a protein that consists of 168 amino acids . The protein contains a central isopeptidase domain, which is responsible for its enzymatic activity. DESI1 is a member of the PPPDE (Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes) family of proteins, which are characterized by their peptidase activity .
DESI1 functions as a protease that specifically deconjugates SUMO1, SUMO2, and SUMO3 from substrate proteins . Unlike other SUMO-specific proteases, DESI1 does not exhibit SUMO-processing activity but rather acts as an isopeptidase. This means that DESI1 cleaves the isopeptide bond between the SUMO protein and the lysine residue of the substrate protein .
One of the key substrates of DESI1 is ZBTB46, a transcriptional repressor. DESI1 catalyzes the desumoylation of ZBTB46, thereby regulating its activity . Additionally, DESI1 collaborates with UBQLN4 in the export of ubiquitinated proteins from the nucleus to the cytoplasm .
The desumoylation process mediated by DESI1 is vital for maintaining cellular homeostasis. SUMOylation and desumoylation are dynamic processes that modulate the function, localization, and stability of proteins. By removing SUMO modifications, DESI1 helps to regulate protein-protein interactions, subcellular localization, and the activity of target proteins .
Mutations or dysregulation of the DESI1 gene have been associated with various diseases. For instance, DESI1 has been linked to pulmonary aspergilloma and Parkinson’s disease 6, an autosomal recessive early-onset form of Parkinson’s disease . Understanding the role of DESI1 in these diseases could provide insights into potential therapeutic targets.
Recombinant DESI1 protein is used in research to study the mechanisms of desumoylation and its impact on cellular processes. By using human recombinant DESI1, researchers can investigate the enzyme’s substrate specificity, catalytic activity, and potential interactions with other proteins. This knowledge can contribute to the development of novel therapeutic strategies for diseases associated with dysregulated SUMOylation.