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Valosin-containing protein (VCP), also known as p97 or CDC48, is an AAA+ ATPase that plays a central role in the ubiquitin-proteasome system (UPS) and endoplasmic reticulum-associated degradation (ERAD). It acts as an unfoldase or segregase, using ATP hydrolysis to extract ubiquitinated substrates from complexes or membranes, facilitating their degradation by the proteasome. VCP is involved in numerous cellular processes, including cell cycle control, membrane fusion, apoptosis prevention, and DNA repair. Mutations or dysregulation in VCP are linked to several human diseases, including IBMPFD, ALS, neurodegeneration, and cardiovascular disorders.
ATP-dependent segregase/unfoldase using cofactors/VCP-interacting motifs (VIMs) to extract ubiquitinated substrates and deliver them to the proteasome for degradation.
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