Valosin-containing protein

VCP
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3EBB, 3HU1, 3HU2, 3HU3, 3QC8, 3QQ7, 3QQ8, 3QWZ, 3TIW, 4KDI, 4KDL, 4KLN, 4KO8, 4KOD, 4P0A, 5C19, 3CF2, 3CF1, 5FTK, 5C18, 3CF3, 5FTJ, 5FTM, 5FTL, 5FTN, 5C1B, 5C1A, 5DYI, 5DYG
Identifiers
Aliases	VCP, ALS14, HEL-220, HEL-S-70, IBMPFD, IBMPFD1, TERA, p97, Valosin-containing protein, CMT2Y, valosin containing protein, CDC48, FTDALS6
External IDs	OMIM: 601023; MGI: 99919; HomoloGene: 5168; GeneCards: VCP; OMA:VCP - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	35,072,668 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	43,000,507 bp
RNA expression pattern
	Top expressed in
	stromal cell of endometrium; ; islet of Langerhans; ; gastrocnemius muscle; ; right adrenal gland; ; right adrenal cortex; ; left adrenal gland; ; left adrenal cortex; ; muscle of thigh; ; ventricular zone; ; minor salivary glands;
	Top expressed in
	muscle of thigh; ; ventricular zone; ; neural layer of retina; ; right kidney; ; lip; ; yolk sac; ; tail of embryo; ; superior frontal gyrus; ; genital tubercle; ; granulocyte;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; protein domain specific binding; protein-containing complex binding; ADP binding; K48-linked polyubiquitin modification-dependent protein binding; polyubiquitin modification-dependent protein binding; protein binding; ubiquitin-like protein ligase binding; ubiquitin-specific protease binding; MHC class I protein binding; protein phosphatase binding; deubiquitinase activator activity; signaling receptor binding; hydrolase activity; ATP binding; ubiquitin protein ligase binding; lipid binding; identical protein binding; ATPase activity; RNA binding; BAT3 complex binding;
Cellular component	site of double-strand break; cytosol; intracellular membrane-bounded organelle; myelin sheath; lipid droplet; nucleoplasm; VCP-NSFL1C complex; endoplasmic reticulum; Derlin-1 retrotranslocation complex; VCP-NPL4-UFD1 AAA ATPase complex; perinuclear region of cytoplasm; proteasome complex; nucleus; extracellular exosome; extracellular region; secretory granule lumen; azurophil granule lumen; ficolin-1-rich granule lumen; ATPase complex; endoplasmic reticulum membrane; cytoplasm; cytoplasmic stress granule; protein-containing complex; synapse; glutamatergic synapse;
Biological process	regulation of aerobic respiration; regulation of apoptotic process; positive regulation of protein catabolic process; positive regulation of protein-containing complex assembly; ubiquitin-dependent protein catabolic process; positive regulation of Lys63-specific deubiquitinase activity; establishment of protein localization; error-free translesion synthesis; viral genome replication; positive regulation of oxidative phosphorylation; ER-associated misfolded protein catabolic process; protein N-linked glycosylation via asparagine; cellular response to DNA damage stimulus; positive regulation of ATP biosynthetic process; endoplasmic reticulum to Golgi vesicle-mediated transport; ATP metabolic process; retrograde protein transport, ER to cytosol; NADH metabolic process; positive regulation of protein K63-linked deubiquitination; double-strand break repair; ubiquitin-dependent ERAD pathway; positive regulation of mitochondrial membrane potential; activation of cysteine-type endopeptidase activity involved in apoptotic process; protein homooligomerization; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein hexamerization; aggresome assembly; flavin adenine dinucleotide catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; autophagy; DNA repair; ERAD pathway; positive regulation of ubiquitin-specific protease activity; autophagosome maturation; translesion synthesis; protein folding; protein methylation; protein deubiquitination; neutrophil degranulation; transmembrane transport; proteasomal protein catabolic process; protein ubiquitination; endoplasmic reticulum unfolded protein response; endoplasmic reticulum stress-induced pre-emptive quality control; macroautophagy; endosome to lysosome transport via multivesicular body sorting pathway; transport; cellular response to heat; stress granule disassembly; regulation of synapse organization; mitotic spindle disassembly; positive regulation of canonical Wnt signaling pathway; cellular response to arsenite ion;
	Sources:Amigo / QuickGO
Orthologs
	7415
	269523
	ENSG00000165280
	ENSMUSG00000028452
	P55072
	Q01853
	NM_007126; NM_001354927; NM_001354928
	NM_009503
	NP_009057; NP_001341856; NP_001341857
	NP_033529
	Wikidata
View/Edit Human	View/Edit Mouse

Valosin-containing protein (VCP) or transitional endoplasmic reticulum ATPase (TER ATPase) also known as p97 in mammals and CDC48 in S. cerevisiae, is an enzyme that in humans is encoded by the VCP gene. The TER ATPase is an ATPase enzyme present in all eukaryotes and archaebacteria. Its main function is to segregate protein molecules from large cellular structures such as protein assemblies, organelle membranes and chromatin, and thus facilitate the degradation of released polypeptides by the multi-subunit protease proteasome.

VCP/p97/CDC48 is a member of the AAA+ (extended family of ATPases associated with various cellular activities) ATPase family. Enzymes of this family are found in all species from bacteria to humans. Many of them are important chaperones that regulate folding or unfolding of substrate proteins. VCP is a type II AAA+ ATPase, which means that it contains two tandem ATPase domains (named D1 and D2, respectively) (Figure 1).

The two ATPase domains are connected by a short polypeptide linker. A domain preceding the D1 domain (N-terminal domain) and a short carboxyl-terminal tail are involved in interaction with cofactors. The N-domain is connected to the D1 domain by a short N-D1 linker.

Most known substrates of VCP are modified with ubiquitin chains and degraded by the 26S proteasome. Accordingly, many VCP coenzymes and adaptors have domains that can recognize ubiquitin. It has become evident that the interplays between ubiquitin and VCP cofactors are critical for many of the proposed functions, although the precise role of these interactions remains to be elucidated.