Ubiquitin specific peptidase 49 (USP49)

Ubiquitin specific peptidase 49 (USP49) is a protein-coding enzyme in the USP family that catalyzes the removal of ubiquitin moieties specifically from histone H2B at lysine 120, a post-translational modification essential for transcriptional regulation and pre-mRNA splicing[1][2]. USP49 is involved in the maintenance of genomic integrity by participating in DNA break repair, antagonizing specific histone and checkpoint ubiquitinations. It regulates alternative splicing genome-wide, influences cell proliferation through the AKT pathway, and impacts antiviral responses by deubiquitinating STING1 and stabilizing APOBEC3G, which is important for HIV restriction[1][2]. Dysregulation of USP49 has been linked to cancer, neurodegenerative conditions, and mitochondrial disorders. As a deubiquitinating enzyme, USP49 represents a potential therapeutic target for modulating chromatin, RNA processing, or immune pathways, although no drugs have reached clinical application for USP49 as of 2025[1][2].

Other names

Ubiquitin carboxyl-terminal hydrolase 49USP49MGC20741Deubiquitinating enzyme 49Ubiquitin thioesterase 49Ubiquitin-specific-processing protease 49Ubiquitin specific protease 49Ubiquitin thiolesterase 49

For hypothetical drugs or tool molecules: inhibition or modulation of USP49 would alter its deubiquitination activity, leading to changes in histone H2B ubiquitination, affecting chromatin structure, splicing efficiency, cell cycle progression, and potentially antiviral or anticancer responses.