MitoSciences: Transitional endoplasmic reticulum ATPase (VCP)

UniProt Number:	P55072
Alternate Names:	TER ATPase, 15S Mg(2+)-ATPase p97 subunit, Valosin-containing protein
Structure and Function:	VCP is necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. It is involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Lastly, VCP regulates E3 ubiquitin-protein ligase activity of RNF19A.
Disease Associations:	Defects in VCP are the cause of inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) [MIM:167320]. IBMPFD features adult-onset proximal and distal muscle weakness (clinically resembling limb girdle muscular dystrophy), early-onset Paget disease of bone in most cases and premature frontotemporal dementia.