Valosin-containing protein

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Valosin containing protein
Protein VCP PDB 1e32.png
PDB rendering based on 1e32.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols VCP ; ALS14; HEL-220; HEL-S-70; IBMPFD; IBMPFD1; TERA; p97
External IDs OMIM601023 MGI99919 HomoloGene5168 ChEMBL: 1075145 GeneCards: VCP Gene
EC number
RNA expression pattern
PBB GE VCP 208649 s at tn.png
PBB GE VCP 208648 at tn.png
More reference expression data
Species Human Mouse
Entrez 7415 269523
Ensembl ENSG00000165280 ENSMUSG00000028452
UniProt P55072 Q01853
RefSeq (mRNA) NM_007126 NM_009503
RefSeq (protein) NP_009057 NP_033529
Location (UCSC) Chr 9:
35.06 – 35.07 Mb
Chr 4:
42.98 – 43 Mb
PubMed search [1] [2]

Transitional endoplasmic reticulum ATPase (TER ATPase) also known as valosin-containing protein (VCP) is an enzyme that in humans is encoded by the VCP gene.[1][2][3]


Valosin-containing protein (VCP) is a type II member of AAA+-ATPase family. It functions as a ubiquitin segregase that remodels multimeric protein complexes by extracting polyubiquitinated proteins for recycling or degradation by the proteasome. VCP subserves a broad array of cellular functions including mitochondrial quality control, autophagy, vesicle transport and fusion, 26S proteasome function, and assembly of peroxisomes. VCP, as a structural protein, is associated with clathrin, and heat-shock protein Hsc70, to form a complex. VCP has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation.[3]


Valosin-containing protein has been shown to interact with AMFR,[4][5] SELS,[6][7] BRCA1,[8] NSFL1C,[9] IκBα[10] and Ataxin 3.[7][11]

Clinical significance[edit]

Mutations in VCP are causative of a pleiotropic degenerative disorder called multisystem proteinopathy or "MSP" that can affect muscle, bone and/or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), inclusion body myopathy (IBM), Paget's disease of bone (PDB), or as a combination of these disorders.[12][13]


  1. ^ Druck T, Gu Y, Prabhala G, Cannizzaro LA, Park SH, Huebner K, Keen JH (April 1996). "Chromosome localization of human genes for clathrin adaptor polypeptides AP2 beta and AP50 and the clathrin-binding protein, VCP". Genomics 30 (1): 94–7. doi:10.1006/geno.1995.0016. PMID 8595912. 
  2. ^ Rabouille C, Levine TP, Peters JM, Warren G (October 1995). "An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments". Cell 82 (6): 905–14. doi:10.1016/0092-8674(95)90270-8. PMID 7553851. 
  3. ^ a b "Entrez Gene: VCP valosin-containing protein". 
  4. ^ Zhong, Xiaoyan; Shen Yuxian; Ballar Petek; Apostolou Andria; Agami Reuven; Fang Shengyun (October 2004). "AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation". J. Biol. Chem. (United States) 279 (44): 45676–84. doi:10.1074/jbc.M409034200. ISSN 0021-9258. PMID 15331598. 
  5. ^ Lee, Joon No; Zhang Xiangyu; Feramisco Jamison D; Gong Yi; Ye Jin (November 2008). "Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step". J. Biol. Chem. (United States) 283 (48): 33772–83. doi:10.1074/jbc.M806108200. ISSN 0021-9258. PMC 2586246. PMID 18835813. 
  6. ^ Ye, Yihong; Shibata Yoko; Yun Chi; Ron David; Rapoport Tom A (June 2004). "A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol". Nature (England) 429 (6994): 841–7. doi:10.1038/nature02656. PMID 15215856. 
  7. ^ a b Wang, Qiuyan; Li Lianyun; Ye Yihong (March 2008). "Inhibition of p97-dependent protein degradation by Eeyarestatin I". J. Biol. Chem. (United States) 283 (12): 7445–54. doi:10.1074/jbc.M708347200. ISSN 0021-9258. PMC 2276333. PMID 18199748. 
  8. ^ Zhang, H; Wang Q; Kajino K; Greene M I (May 2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells". DNA Cell Biol. (UNITED STATES) 19 (5): 253–63. doi:10.1089/10445490050021168. ISSN 1044-5498. PMID 10855792. 
  9. ^ Uchiyama, Keiji; Jokitalo Eija; Lindman Mervi; Jackman Mark; Kano Fumi; Murata Masayuki; Zhang Xiaodong; Kondo Hisao (June 2003). "The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle". J. Cell Biol. (United States) 161 (6): 1067–79. doi:10.1083/jcb.200303048. ISSN 0021-9525. PMC 2173005. PMID 12810701. 
  10. ^ Dai, R M; Chen E; Longo D L; Gorbea C M; Li C C (February 1998). "Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha". J. Biol. Chem. (UNITED STATES) 273 (6): 3562–73. doi:10.1074/jbc.273.6.3562. ISSN 0021-9258. PMID 9452483. 
  11. ^ Doss-Pepe, Ellen W; Stenroos Edward S; Johnson William G; Madura Kiran (September 2003). "Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis". Mol. Cell. Biol. (United States) 23 (18): 6469–83. doi:10.1128/MCB.23.18.6469-6483.2003. ISSN 0270-7306. PMC 193705. PMID 12944474. 
  12. ^ Lucas GJ, Mehta SG, Hocking LJ, Stewart TL, Cundy T, Nicholson GC, Walsh JP, Fraser WD, Watts GD, Ralston SH, Kimonis VE (February 2006). "Evaluation of the role of Valosin-containing protein in the pathogenesis of familial and sporadic Paget's disease of bone.". Bone 38 (2): 280–5. doi:10.1016/j.bone.2005.07.014. PMID 16199218. 
  13. ^ Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, Gibbs JR, Brunetti M, Gronka S, Wuu J, Ding J, McCluskey L, Martinez-Lage M, Falcone D, Hernandez DG, Arepalli S, Chong S, Schymick JC, Rothstein J, Landi F, Wang Y-D, Calvo A, Mora G, Sabatelli M, Monsurrò MR, Battistini S, Salvi F, Spataro R, Sola P, Borghero G, The ITALSGEN Consortium, Galassi G, Scholz SW, Taylor JP, Restagno G, Chiò1 A, Traynor BJ (December 2010). "Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS.". Neuron 68 (5): 857–64. doi:10.1016/j.neuron.2010.11.036. PMC 3032425. PMID 21145000. 

Further reading[edit]

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