OTUD2 Protein, Human

OTUD2, a hydrolase with pivotal roles in cellular processes, is actively involved in endoplasmic reticulum-associated degradation (ERAD) by removing conjugated ubiquitin from misfolded lumenal proteins. It contributes to the ERAD mechanism by potentially trimming ubiquitin chains on associated substrates, facilitating their passage through the VCP/p97 pore. Specifically, OTUD2 exhibits deubiquitination activity towards 'Lys-27', 'Lys-29', and 'Lys-33'-linked polyubiquitin chains, as well as 'Lys-11'-linked ubiquitin chains. The ability to cleave both polyubiquitin and di-ubiquitin underscores its versatility. Beyond ERAD, OTUD2 may play a crucial role in macroautophagy, influencing the clearance of damaged lysosomes. Its involvement in autophagy includes recruiting PLAA, UBXN6, and VCP to damaged lysosome membranes adorned with K48-linked ubiquitin chains, facilitating their removal and promoting autophagosome formation. This multifaceted functionality highlights OTUD2's significance in cellular quality control mechanisms.