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Ubiquitin-like 3 (UBL3) is a well-conserved ubiquitin-like protein (UBL) in eukaryotes and regulates the ubiquitin cascade, but the significant roles of UBL3 in cellular processes remained unknown. Recently, UBL3 was elucidated to be a post-translational modification factor that promotes protein sorting to small extracellular vesicles (sEVs). Proteins sorted into sEVs have been studied as etiologies of sEV-related diseases. Also, there have been attempts to construct drug delivery systems (DDSs) by loading proteins into sEVs. In this review, we introduce the new concept that UBL3 has a critical role in the protein-sorting system and compare structure conservation between UBL3 and other UBLs from an evolutionary perspective. We conclude with future perspectives for the utility of UBL3 in sEV-related diseases and DDS.Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification.

Citation

Yusuke Takanashi, Tomoaki Kahyo, Sae Kamamoto, Hengsen Zhang, Bin Chen, Yashuang Ping, Kiyomichi Mizuno, Akikazu Kawase, Kei Koizumi, Masanori Satou, Kazuhito Funai, Norihiko Shiiya, Mitsutoshi Setou. Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles. Cell structure and function. 2022;47(1):1-18

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PMID: 35197392

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