Transitional endoplasmic reticulum ATPase (TER ATPase) also known as valosin-containing protein (VCP) is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that in humans is encoded by the VCP gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Function

Valosin-containing protein (VCP) is a member of a family that includes putative ATP-binding proteins involved in vesicle

Vesicle (biology)

A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 transport and fusion, 26S proteasome

Proteasome

Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria.  In eukaryotes, they are located in the nucleus and the cytoplasm.  The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...

 function, and assembly of peroxisome

Peroxisome

Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...

s. VCP, as a structural protein, is associated with clathrin

Clathrin

Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...

, and heat-shock protein Hsc70

Hsc70

Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene.- Function :...

, to form a complex. VCP has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion

Lipid bilayer fusion

Fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. If this fusion proceeds completely through both leaflets of both bilayers, an aqueous bridge is formed and the internal contents of the two structures can mix...

, spindle pole body

Spindle pole body

The spindle pole body is the microtubule organizing center in yeast cells, functionally equivalent to the centrosome. Unlike the centrosome the SPB does not contain centrioles. The SPB organises the microtubule cytoskeleton which plays many roles in the cell...

 function, and ubiquitin

Ubiquitin

Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

-dependent protein degradation.

Interactions

Valosin-containing protein has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with AMFR

AMFR

Autocrine motility factor receptor, isoform 2 is a protein that in humans is encoded by the AMFR gene.-Interactions:AMFR has been shown to interact with Valosin-containing protein.-Further reading:...

, SELS

SELS (gene)

Selenoprotein S, also known as SELS, is a human gene.-Interactions:SELS has been shown to interact with Valosin-containing protein.-Further reading:...

, BRCA1

BRCA1

BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...

, NSFL1C

NSFL1C

NSFL1 cofactor p47 is a protein that in humans is encoded by the NSFL1C gene.-Interactions:NSFL1C has been shown to interact with Valosin-containing protein.-Further reading:...

, IκBα and Ataxin 3

Ataxin 3

Ataxin-3 is a protein that in humans is encoded by the ATXN3 gene.-Interactions:Ataxin 3 has been shown to interact with RAD23A, Valosin-containing protein and RAD23B.-External Links:* -Further reading:...

.

Clinical significance

Mutations in VCP have been linked to inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia (IBMPFD

Hereditary inclusion body myopathy

Hereditary inclusion body myopathies are a heterogeneous group of genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults...

). They may also be linked to familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

.

External links

• GeneReviews/NIH/NCBI/UW entry on Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia