VCP : valosin containing protein

Description

The VCP (valosin containing protein) is a protein-coding gene located on chromosome 9.

The VCP gene provides instructions for making an enzyme called valosin-containing protein. This enzyme is found throughout the body and has a wide variety of functions within cells. It is involved in cell division, joining (fusing) membranes within cells, reassembling cell structures after cells have divided, preventing the self-destruction of cells (apoptosis), and repairing damaged DNA. Valosin-containing protein is part of the ubiquitin-proteasome system, which is the machinery that breaks down (degrades) unneeded proteins within cells. This system provides quality control by disposing of damaged, misshapen, and excess proteins. It also regulates the level of proteins involved in several critical cell activities, such as the timing of cell division and growth. Researchers believe that most of the functions of valosin-containing protein are directly or indirectly related to the ubiquitin-proteasome system.

VCP is an essential protein that plays a role in a wide variety of cellular processes, including membrane trafficking, protein degradation, DNA repair, and autophagy. It is involved in the fragmentation and reassembly of Golgi stacks during mitosis, the formation of the transitional endoplasmic reticulum (tER), and the export of misfolded proteins from the ER to the cytoplasm for degradation by the proteasome. VCP also regulates spindle disassembly at the end of mitosis, contributes to the formation of a closed nuclear envelope, and mediates the endoplasmic reticulum-associated degradation (ERAD) of specific proteins, including HMGCR and CHRNA3. Furthermore, VCP is involved in DNA damage response, specifically by recruiting TP53BP1 to double-strand breaks and promoting the repair of covalent DNA-protein cross-links. It also acts as a negative regulator of type I interferon production by interacting with RIGI and promoting its degradation. In addition, VCP may play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes and in the sorting of caveolins. VCP also regulates the insulin-like growth factor receptor signaling pathway by controlling the steady-state expression of the IGF1R receptor.

VCP is also known as CDC48, FTDALS6, TERA, p97.

Associated Diseases

• Behavioral variant of frontotemporal dementia
• Autosomal dominant Charcot-Marie-Tooth disease type 2Y
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 6
• Charcot-Marie-Tooth disease, axonal, type 2Y
• Inclusion body myopathy with early-onset paget disease with or without frontotemporal dementia 1
• Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
• Amyotrophic lateral sclerosis
• Progressive non-fluent aphasia
• Adult-onset distal myopathy due to VCP mutation
• Spastic paraplegia-Paget disease of bone syndrome
• Frontotemporal dementia with motor neuron disease
• Charcot-Marie-Tooth disease
• Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia