Valosin-containing protein

Valosin containing protein
PDB rendering based on 1e32.
Available structures PDB 3EBB, 3HU1, 3HU2, 3HU3
Identifiers
Symbols	VCP; IBMPFD; MGC131997; MGC148092; MGC8560; TERA; p97
External IDs	OMIM: 601023 MGI: 99919 HomoloGene: 5168 GeneCards: VCP Gene
Gene Ontology Molecular function • nucleotide binding • protein binding • ATP binding • lipid binding • hydrolase activity • ATPase activity • protein phosphatase binding • protein domain specific binding • polyubiquitin binding • protein complex binding • identical protein binding Cellular component • proteasome complex • nucleus • nucleus • nucleolus • cytoplasm • endoplasmic reticulum • microsome • cytosol Biological process • ATP catabolic process • DNA repair • double-strand break repair • transport • ER to Golgi vesicle-mediated transport • activation of caspase activity • response to DNA damage stimulus • protein ubiquitination • ER-associated protein catabolic process • endoplasmic reticulum unfolded protein response • retrograde protein transport, ER to cytosol • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • regulation of apoptosis • proteasomal ubiquitin-dependent protein catabolic process • establishment of protein localization • positive regulation of protein catabolic process • protein homooligomerization • aggresome assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7415	269523
Ensembl	ENSG00000165280	ENSMUSG00000028452
UniProt	P55072	Q01853
RefSeq (mRNA)	NM_007126	NM_009503.4
RefSeq (protein)	NP_009057	NP_033529.3
Location (UCSC)	Chr 9: 35.06 – 35.07 Mb	Chr 4: 42.99 – 43.01 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.

Function

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

Interactions

Valosin-containing protein has been shown to interact with AMFR, SELS, BRCA1, NSFL1C, IκBα and Ataxin 3.

Clinical significance

Mutations in VCP have been linked to inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia (IBMPFD). They may also be linked to familial amyotrophic lateral sclerosis.

Further reading

• Guinto JB, Ritson GP, Taylor JP, Forman MS (2007). "Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy.". Acta Neuropathol. 114 (1): 55–61. doi:10.1007/s00401-007-0224-7. PMID 17457594. 
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
• Pleasure IT, Black MM, Keen JH (1993). "Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein.". Nature 365 (6445): 459–62. doi:10.1038/365459a0. PMID 8413590. 
• Germain-Lee EL, Obie C, Valle D (1997). "NVL: a new member of the AAA family of ATPases localized to the nucleus.". Genomics 44 (1): 22–34. doi:10.1006/geno.1997.4856. PMID 9286697. 
• Hoyle J, Tan KH, Fisher EM (1997). "Mapping the valosin-containing protein (VCP) gene on human chromosome 9 and mouse chromosome 4, and a likely pseudogene on the mouse X chromosome.". Mamm. Genome 8 (10): 778–80. doi:10.1007/s003359900566. PMID 9321476. 
• Dai RM, Chen E, Longo DL, et al. (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. 273 (6): 3562–73. doi:10.1074/jbc.273.6.3562. PMID 9452483. 
• Rabouille C, Kondo H, Newman R, et al. (1998). "Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro.". Cell 92 (5): 603–10. doi:10.1016/S0092-8674(00)81128-9. PMID 9506515. 
• Zhang SH, Liu J, Kobayashi R, Tonks NK (1999). "Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1.". J. Biol. Chem. 274 (25): 17806–12. doi:10.1074/jbc.274.25.17806. PMID 10364224. 
• Zhang H, Wang Q, Kajino K, Greene MI (2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.". DNA Cell Biol. 19 (5): 253–63. doi:10.1089/10445490050021168. PMID 10855792. 
• Hu RM, Han ZG, Song HD, et al. (2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16901. 
• Lavoie C, Chevet E, Roy L, et al. (2001). "Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro.". Proc. Natl. Acad. Sci. U.S.A. 97 (25): 13637–42. doi:10.1073/pnas.240278097. PMC 17628. PMID 11087817. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17628. 
• Kimonis VE, Kovach MJ, Waggoner B, et al. (2001). "Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone.". Genet. Med. 2 (4): 232–41. PMID 11252708. 
• Seigneurin-Berny D, Verdel A, Curtet S, et al. (2001). "Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways.". Mol. Cell. Biol. 21 (23): 8035–44. doi:10.1128/MCB.21.23.8035-8044.2001. PMC 99970. PMID 11689694. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99970. 
• Yang CS, Weiner H (2002). "Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol.". Arch. Biochem. Biophys. 400 (1): 105–10. doi:10.1006/abbi.2002.2778. PMID 11913976. 
• Asai T, Tomita Y, Nakatsuka S, et al. (2002). "VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line.". Jpn. J. Cancer Res. 93 (3): 296–304. PMID 11927012. 
• Kobayashi T, Tanaka K, Inoue K, Kakizuka A (2003). "Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells.". J. Biol. Chem. 277 (49): 47358–65. doi:10.1074/jbc.M207783200. PMID 12351637. 
• Uchiyama K, Jokitalo E, Kano F, et al. (2003). "VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo.". J. Cell Biol. 159 (5): 855–66. doi:10.1083/jcb.200208112. PMC 2173386. PMID 12473691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173386. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 

External links

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