{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Redirect|P97}} {{Infobox_gene}} '''Valosin-containing protein''' ('''VCP''') or '''transitional endoplasmic reticulum ATPase''' ('''TER ATPase''') also known as '''p97''' in mammals and [[CDC48 N-terminal domain|CDC48]] in ''[[S. cerevisiae]],'' is an [[enzyme]] that in humans is encoded by the ''VCP'' [[gene]].<ref name="pmid8595912">{{cite journal | vauthors = Druck T, Gu Y, Prabhala G, Cannizzaro LA, Park SH, Huebner K, Keen JH | date = November 1995 | title = Chromosome localization of human genes for clathrin adaptor polypeptides AP2 beta and AP50 and the clathrin-binding protein, VCP | journal = Genomics | volume = 30 | issue = 1 | pages = 94–97 | doi = 10.1006/geno.1995.0016 | pmid = 8595912 }}</ref><ref name = "Rabouille_1995"/><ref name="entrez">{{cite web | title = Entrez Gene: VCP valosin-containing protein| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7415}}</ref> The TER ATPase is an [[ATPase]] enzyme present in all [[eukaryote]]s and [[Archaea]]. 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 [[chaperone (protein)|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'''). [[File:VCP Wiki Figure 1.jpg|thumb|Figure 1- A schematic diagram of the p97 domain structure.]] 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.<ref name = "Ogura_2001"/> 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.<ref name = "Ye_2006"/> 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.
== Discovery ==
CDC48 was discovered in a [[genetic screen]] for genes involved in [[cell cycle]] regulation in ''budding yeast''.<ref name = "Moir_1982"/> The screen identified several alleles of ''Cdc48'' that affect cell growth at non-permissive temperatures. A search for the mammalian homolog of CDC48 (valosin) revealed a 97 kDa [[protein precursor]] named "valosin-containing protein (VCP)" or p97, and also showed that it was only generated as an artefact of purification rather than during physiological processing.<ref name = "Koller_1987"/> Even without evidence that valosin is a physiological product, the VCP nomenclature continues to be used in the literature.
== Tissue and subcelluar distribution ==
VCP is one of the most abundant cytoplasmic proteins in eukaryotic cells. It is ubiquitously expressed in all tissues in multicellular organisms. In humans, the mRNA expression of VCP was found to be moderately elevated in certain types of cancer.<ref name = "Ye_2006"/>
In mammalian cells, VCP is predominantly localized to the [[cytoplasm]], and a significant fraction is associated to membranes of cellular organelles such as the [[endoplasmic reticulum]] (ER), Golgi, mitochondria, and endosomes.<ref name = "Rabouille_1995"/><ref name = "Acharya_1995"/><ref name = "Latterich_1995"/><ref name = "Xu_2011"/><ref name = "Ramanathan_2012"/> The subcellular localization of CDC48 has not been fully characterized, but is likely to be similar to the mammalian counterpart. A fraction of VCP was also found in the nucleus.<ref name = "Madeo_1998"/>
== Structure ==
According to the crystal structures of full-length wild-type VCP,<ref name = "DeLaBarre_2003"/><ref name = "Davies_2008"/> six VCP subunits assemble into a barrel-like structure, in which the N-D1 and D2 domains form two concentric, stacked rings ('''Figure''' '''2'''). [[File:VCP Wiki Figure 2.jpg|thumb|Figure 2- The structure of VCP. The six subunits are shown as molecular surface in different colors. Domains of each subunit are also shaded differently. Two views are presented. This structure represents VCP in an ADP bound state.]] The N-D1 ring is larger (162 Å in diameter) than the D2 ring (113 Å) due to the laterally attached N-domains. The D1 and D2 domains are highly homologous in both sequence and structure, but they serve distinct functions. For example, the hexameric assembly of VCP only requires the D1 but not the D2 domain.<ref name = "Wang_2003"/> Unlike many bacterial AAA+ proteins, assembly of VCP hexamer does not depend on the presence of nucleotide. The VCP hexameric assembly can undergo dramatic conformational changes during nucleotide hydrolysis cycle,<ref name = "Beuron_2006"/><ref name = "Beuron_2003"/><ref name = "DeLaBarre_2006a"/><ref name = "Rouiller_2002"/><ref name = "Tang_23010"/> and it is generally believed that these conformational changes generate mechanical force, which is applied to substrate molecules to influence their stability and function. However, how precisely VCP generates force is unclear.
== The ATP hydrolysis cycle ==
The ATP hydrolyzing activity is indispensable for the VCP functions.<ref name = "Wang_2004"/> The two ATPase domains of VCP (D1 and D2) are not equivalent because the D2 domain displays higher ATPase activity than the D1 domain in wild-type protein. Nevertheless, their activities are dependent of each other.<ref name = "Nishikori_2011"/><ref name = "Tang_2013"/><ref name = "Ye_2003"/><ref name = "Song_2003"/> For example, nucleotide binding to the D1 domain is required for ATP binding to the D2 domain and nucleotide binding and hydrolysis in D2 is required for the D1 domain to hydrolyze ATP.
The ATPase activity of VCP can be influenced by many factors. For example, it can be stimulated by heat<ref name = "Song_2003"/> or by a putative substrate protein.<ref name = "DeLaBarre_2006b"/> In ''Leishmania infantum'', the ''Li''VCP protein is essential for the intracellular development of the parasite and its survival under heat stress.<ref name=pmid29895095>{{cite journal | vauthors = Guedes Aguiar B, Padmanabhan PK, Dumas C, Papadopoulou B | title = Valosin-containing protein VCP/p97 is essential for the intracellular development of Leishmania and its survival under heat stress | journal = Cellular Microbiology | volume = 20 | issue = 10 | article-number = e12867 | date = June 2018 | pmid = 29895095 | doi = 10.1111/cmi.12867 | s2cid = 48359590 | doi-access = free }}</ref> Association with cofactors can have either positive or negative impact on the p97 ATPase activity.<ref name = "Meyer_1998"/><ref name = "Zhang_2015"/>
Mutations in VCP can also influence its activity. For example, VCP mutant proteins carrying single point mutations found in patients with [[multisystem proteinopathy]] (MSP; formerly known as IBMPFD (inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia)) (see below) have 2-3 fold increase in ATPase activity.<ref name = "Tang_2013"/><ref name = "Halawani_2009"/><ref name = "Weihl_2006"/>
== VCP-interacting proteins ==
Recent proteomic studies have identified a large number of p97-interacting proteins. Many of these proteins serve as adaptors that link VCP to a particular subcellular compartment to function in a specific cellular pathway. Others function as adaptors that recruit substrates to VCP for processing. Some VCP-interacting proteins are also enzymes such as N-glycanase, [[ubiquitin ligase]], and deubiquitinase, which assist VCP in processing substrates.
Most cofactors bind VCP through its N-domain, but a few interact with the short carboxy-terminal tail in VCP. Representative proteins interacting with the N-domain are Ufd1, Npl4, p47 and FAF1.<ref name = "Ye_2001"/><ref name = "Kondo_1997"/><ref name = "Song_2005"/> Examples of cofactors that interact with the carboxy-terminal tail of VCP are PLAA, PNGase, and Ufd2.<ref name="Qiu_2010"/><ref name="Zhao_2007"/><ref name="Schaeffer_2014"/>
The molecular basis for cofactor binding has been studied for some cofactors that interact with the VCP N-domain. The N-domain consists of two sub-domains of roughly equal size: the N-terminal double Y-barrel and a C-terminal b-barrel ('''Figure 3'''). [[File:VCP Wiki Figure 3.jpg|thumb|Figure 3- Structure of the N-domain of VCP. The N-domain is depicted as a molecular surface superimposed to a ribbon representation.]] Structural studies show that many cofactor proteins bind to the N-domain at a cleft formed between the two sub-domains.
Among those that bind to the N-domain of VCP, two most frequently occurring sequence motifs are found: one is called UBX motif (ubiquitin regulatory X)<ref name = "Schuberth_2008"/> and the other is termed VIM (VCP-interacting motif).<ref name = "Stapf_2011"/> The UBX domain is an 80-residue module with a fold highly resembling the structure of ubiquitin. The VCP-interacting motif (VIM) is a linear sequence motif (RX<sub>5</sub>AAX<sub>2</sub>R) found in a number of VCP cofactors including gp78,<ref name = "Ballar_2006"/> SVIP (small VCP-interacting protein)<ref name = "Ballar_2007"/> and VIMP (VCP interacting membrane protein).<ref name = "Ye_2004"/> Although the UBX domain uses a surface loop whereas the VIM forms a-helix to bind VCP, both UBX and VIM bind at the same location between the two sub-domains of the N-domain ('''Figure 3''').<ref name = "Hänzelmann_2011"/> It was proposed that hierarchical binding to distinct cofactors may be essential for the broad functions of VCP.<ref name = "Meyer_2000"/><ref name = "Buchberger_2015"/>
== Function ==
VCP performs diverse functions through modulating the stability and thus the activity of its substrates. The general function of VCP is to segregate proteins from large protein assembly or immobile cellular structures such as membranes or chromatin, allowing the released protein molecules to be degraded by the proteasome. The functions of VCP can be grouped into the following three major categories.
=== Protein quality control ===
The best characterized function of VCP is to mediate a network of protein quality control processes in order to maintain protein homeostasis.<ref name = "Meyer_2012"/> These include endoplasmic reticulum-associated protein degradation (ERAD) and mitochondria-associated degradation.<ref name = "Xu_2011"/><ref name = "Christianson_2014"/> In these processes, ATP hydrolysis by VCP is required to extract aberrant proteins from the membranes of the ER or mitochondria. VCP is also required to release defective translation products stalled on ribosome in a process termed ribosome-associated degradation.<ref name = "Brandman_2012"/><ref name = "Defenouillère_2013"/><ref name = "Verma_2013"/> It appears that only after extraction from the membranes or large protein assembly like ribosome, can polypeptides be degraded by the proteasome. In addition to this 'segregase' function, VCP might have an additional role in shuttling the released polypeptides to the proteasome. This chaperoning function seems to be particularly important for degradation of certain aggregation-prone misfolded proteins in nucleus.<ref name = "Gallagher_2014"/> Several lines of evidence also implicate p97 in autophagy, a process that turns over cellular proteins (including misfolded ones) by engulfing them into double-membrane-surrounded vesicles named autophagosome, but the precise role of VCP in this process is unclear.<ref name = "Bug_2012"/>
=== Chromatin-associated functions ===
VCP also functions broadly in eukaryotic nucleus by releasing protein molecules from chromatins in a manner analogous to that in ERAD.<ref name = "Dantuma_2014"/> The identified VCP substrates include transcriptional repressor α2 and RNA polymerase (Pol) II complex and CMG DNA helicase in budding yeast, and the DNA replicating licensing factor CDT1, DNA repairing proteins DDB2 and XPC, mitosis regulator Aurora B, and certain DNA polymerases in mammalian cells. These substrates link VCP function to gene transcription, DNA replication and repair, and cell cycle progression.
=== Membrane fusion and trafficking ===
Biochemical and genetic studies have also implicated VCP in fusion of vesicles that lead to the formation of Golgi apparatus at the end of mitosis.<ref name = "Uchiyama_2005"/> This process requires the ubiquitin binding adaptor p47 and a p97-associated deubiquitinase VCIP135, and thus connecting membrane fusion to the ubiquitin pathways. However, the precise role of VCP in Golgi formation is unclear due to lack of information on relevant substrate(s). Recent studies also suggest that VCP may regulate vesicle trafficking from plasma membrane to the lysosome, a process termed endocytosis.<ref name = "Bug_2012"/> Antibody fragment-based inhibitors have been developed by a team led by [[Michelle R. Arkin|Arkin]] to inhibit the interaction between p97 and p47, selectively modulating the Golgi reassembly process.<ref>{{cite journal | vauthors = Jiang Z, Kuo YH, Zhong M, Zhang J, Zhou XX, Xing L, Wells JA, Wang Y, Arkin MR | date = July 2022 | title = Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions | journal = Journal of the American Chemical Society | volume = 144 | issue = 29 | pages = 13218–13225 | doi = 10.1021/jacs.2c03665 | pmc = 9335864 | pmid = 35819848 | bibcode = 2022JAChS.14413218J }}</ref>
== Clinical significance ==
=== Links to human diseases === Mutations in VCP were first reported to cause a syndrome characterized by [[frontotemporal dementia]], [[Hereditary inclusion body myopathy|inclusion body myopathy]], and [[Paget's disease of bone|Paget's disease of the bone]] by Virginia Kimonis in 2004.<ref>{{cite journal | vauthors = Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, Pestronk A, Whyte MP, Kimonis VE | title = Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein | journal = Nature Genetics | volume = 36 | issue = 4 | pages = 377–381 | date = April 2004 | pmid = 15034582 | doi = 10.1038/ng1332 | doi-access = free }}</ref> In 2010, mutations in VCP were also found to be a cause of [[amyotrophic lateral sclerosis]] by [[Bryan J. Traynor|Bryan Traynor]] and Adriano Chiò.<ref>{{cite journal | vauthors = 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 YD, Calvo A, Mora G, Sabatelli M, Monsurrò MR, Battistini S, Salvi F, Spataro R, Sola P, Borghero G, Galassi G, Scholz SW, Taylor JP, Restagno G, Chiò A, Traynor BJ | title = Exome sequencing reveals VCP mutations as a cause of familial ALS | journal = Neuron | volume = 68 | issue = 5 | pages = 857–864 | date = December 2010 | pmid = 21145000 | doi = 10.1016/j.neuron.2010.11.036 | pmc = 3032425 }}</ref> This discovery was notable as it represented an initial genetic link between two disparate neurological diseases, amyotrophic lateral sclerosis and frontotemporal dementia. In 2020, Edward Lee described a distinct hypomorphic mutation in VCP associated with vacuolar tauopathy, a unique subtype of frontotemporal lobar degeneration with tau inclusions.<ref>{{cite journal | vauthors = Darwich NF, Phan JM, Kim B, Suh E, Papatriantafyllou JD, Changolkar L, Nguyen AT, O'Rourke CM, He Z, Porta S, Gibbons GS, Luk KC, Papageorgiou SG, Grossman M, Massimo L, Irwin DJ, McMillan CT, Nasrallah IM, Toro C, Aguirre GK, Van Deerlin VM, Lee EB | date = November 2020 | title = Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau | journal = Science | volume = 370 | issue = 6519 | article-number = eaay8826 | doi = 10.1126/science.aay8826 | pmc = 7818661 | pmid = 33004675 }}</ref>
Mutations in VCP are an example of [[pleiotropy]], where mutations in the same gene give rise to different phenotypes. The term [[multisystem proteinopathy]] (MSP) has been coined to describe this particular form of pleiotropy.<ref>{{cite journal | vauthors = Taylor JP | title = Multisystem proteinopathy: intersecting genetics in muscle, bone, and brain degeneration | journal = Neurology | volume = 85 | issue = 8 | pages = 658–660 | date = August 2015 | pmid = 26208960 | doi = 10.1212/WNL.0000000000001862 | s2cid = 42203997 }}</ref> Although MSP is rare, growing interest in this syndrome derives from the molecular insights the condition provides into the etiological relationship between common age-related degenerative diseases of muscle, bone and brain. It has been estimated that ~50% of MSP may be caused by missense mutations affecting the valosin-containing protein (VCP) gene.<ref>{{cite journal | vauthors = Le Ber I, Van Bortel I, Nicolas G, Bouya-Ahmed K, Camuzat A, Wallon D, De Septenville A, Latouche M, Lattante S, Kabashi E, Jornea L, Hannequin D, Brice A | title = hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem proteinopathy" and frontotemporal lobar degeneration phenotypes | journal = Neurobiology of Aging | volume = 35 | issue = 4 | pages = 934.e5–6 | date = April 2014 | pmid = 24119545 | doi = 10.1016/j.neurobiolaging.2013.09.016 | s2cid = 207160856 }}</ref>
=== Cancer therapy ===
The first p97 inhibitor [[Eeyarestatin]] (EerI) was discovered by screening and characterizing compounds that inhibit the degradation of a fluorescence-labeled ERAD substrate.<ref name = "Fiebiger_2004"/><ref name = "Wang_2010"/> The mechanism of VCP inhibition by EerI is unclear, but when applied to cells, it induces biological phenotypes associated with VCP inhibition such as ERAD inhibition, ER stress elevation, and apoptosis induction. Importantly, EerI displays significant cancer-killing activity ''in vitro'' preferentially against cancer cells isolated from patients, and it can synergize with the proteasome inhibitor [[bortezomib]] to kill cancer cells.<ref name = "Wang_2009"/> These observations prompt the idea of targeting VCP as a potential cancer therapy. This idea was further confirmed by studying several ATP competitive and allosteric inhibitors.<ref name = "Chou_2013"/><ref name = "Chou_2011"/><ref name = "Magnaghi_2013"/> More recently, a potent and specific VCP inhibitor CB-5083 has been developed, which demonstrates promising anti-cancer activities in mouse xenograft tumor models.<ref name = "Anderson_2015"/> The compound is now being evaluated in a phase 1 clinical trial.<ref name = "Nold_2016">{{cite journal | vauthors = Zhou HJ, Wang J, Yao B, Wong S, Djakovic S, Kumar B, Rice J, Valle E, Soriano F, Menon MK, Madriaga A, Kiss von Soly S, Kumar A, Parlati F, Yakes FM, Shawver L, Le Moigne R, Anderson DJ, Rolfe M, Wustrow D | date = December 2015 | title = Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the VCP AAA ATPase (CB-5083) | journal = Journal of Medicinal Chemistry | volume = 58 | issue = 24 | pages = 9480–9497 | doi = 10.1021/acs.jmedchem.5b01346 | doi-access = free | pmid = 26565666 }}</ref>
== Conferences ==
Since the mid-2010s, a series of international meetings have been held to coordinate research and clinical understanding of disorders caused by ''VCP'' gene variants. The first expert workshop, convened by the European Neuromuscular Centre (ENMC) in 2015, established a shared clinical framework and research priorities for what were then termed ''VCP''-related multisystem [[proteinopathy|proteinopathies]].<ref name="ENMC2015">{{cite journal | vauthors = Evangelista T, Weihl CC, Kimonis V, Lochmüller H | title = 215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13-15 November 2015, Heemskerk, The Netherlands | language = English | journal = Neuromuscular Disorders | volume = 26 | issue = 8 | pages = 535–547 | date = August 2016 | pmid = 27312024 | pmc = 5967615 | doi = 10.1016/j.nmd.2016.05.017 }}</ref> Subsequent conferences in 2021 and 2024 brought together academic researchers, clinicians, and patient-advocacy groups to review advances in molecular mechanisms, diagnostic approaches, and therapeutic development.<ref name="VCP2021">{{cite journal | vauthors = Johnson MA, Klickstein JA, Khanna R, Gou Y, Raman M | title = The Cure VCP Scientific Conference 2021: Molecular and clinical insights into neurodegeneration and myopathy linked to multisystem proteinopathy-1 (MSP-1) | journal = Neurobiology of Disease | volume = 169 | issue = | article-number = 105722 | date = July 2022 | pmid = 35405261 | pmc = 9169230 | doi = 10.1016/j.nbd.2022.105722 }}</ref><ref>{{cite journal | vauthors = Peck A, Dadi A, Yavarow Z, Alfano LN, Anderson D, Arkin MR, Chou TF, D'Ambrosio ES, Diaz-Manera J, Dudley JP, Elder AG, Ghoshal N, Hart CE, Hart MM, Huryn DM, Johnson AE, Jones KB, Kimonis V, Kiskinis E, Lee EB, Lloyd TE, Mapstone M, Martin A, Meyer H, Mozaffar T, Onyike CU, Pfeffer G, Pindon A, Raman M, Richard I, Rubinsztein DC, Schiava M, Schütz AK, Shen PS, Southworth DR, Staffaroni AM, Taralio-Gravovac M, Weihl CC, Yao Q, Ye Y, Peck N | title = 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy | journal = Neurobiology of Disease | volume = 207 | article-number = 106861 | date = April 2025 | pmid = 40037468 | pmc = 11960434 | doi = 10.1016/j.nbd.2025.106861 }}</ref> These meetings have contributed to the formation of ongoing international collaborations and patient registries dedicated to ''VCP''-associated diseases.
== Notes == {{Academic-written review|Q=Q36767612}}
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18 <ref name = "Tang_23010">{{cite journal | vauthors = Tang WK, Li D, Li CC, Esser L, Dai R, Guo L, Xia D | date = July 2010 | title = A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants | journal = The EMBO Journal | volume = 29 | issue = 13 | pages = 2217–2229 | doi = 10.1038/emboj.2010.104 | pmc = 2905243 | pmid = 20512113 }}</ref>
19 <ref name = "Wang_2004">{{cite journal | vauthors = Wang Q, Song C, Li CC | title = Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions | journal = Journal of Structural Biology | volume = 146 | issue = 1–2 | pages = 44–57 | year = 2004 | pmid = 15037236 | doi = 10.1016/j.jsb.2003.11.014 | url = https://zenodo.org/record/1259179 }}</ref>
20 <ref name = "Nishikori_2011">{{cite journal | vauthors = Nishikori S, Esaki M, Yamanaka K, Sugimoto S, Ogura T | date = May 2011 | title = Positive cooperativity of the p97 AAA ATPase is critical for essential functions | journal = The Journal of Biological Chemistry | volume = 286 | issue = 18 | pages = 15815–15820 | doi = 10.1074/jbc.M110.201400 | doi-access = free | pmc = 3091191 | pmid = 21454554 }}</ref>
21 <ref name = "Tang_2013">{{cite journal | vauthors = Tang WK, Xia D | date = December 2013 | title = Altered intersubunit communication is the molecular basis for functional defects of pathogenic p97 mutants | journal = The Journal of Biological Chemistry | volume = 288 | issue = 51 | pages = 36624–36635 | doi = 10.1074/jbc.M113.488924 | doi-access = free | pmc = 3868774 | pmid = 24196964 }}</ref>
22 <ref name = "Ye_2003">{{cite journal | vauthors = Ye Y, Meyer HH, Rapoport TA | title = Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains | journal = The Journal of Cell Biology | volume = 162 | issue = 1 | pages = 71–84 | date = July 2003 | pmid = 12847084 | pmc = 2172719 | doi = 10.1083/jcb.200302169 }}</ref>
23 <ref name = "Song_2003">{{cite journal | vauthors = Song C, Wang Q, Li CC | date = February 2003 | title = ATPase activity of p97-valosin-containing protein (VCP). D2 mediates the major enzyme activity, and D1 contributes to the heat-induced activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3648–3655 | doi = 10.1074/jbc.M208422200 | doi-access = free | pmid = 12446676 }}</ref>
24 <ref name = "DeLaBarre_2006b">{{cite journal | vauthors = DeLaBarre B, Christianson JC, Kopito RR, Brunger AT | date = May 2006 | title = Central pore residues mediate the p97/VCP activity required for ERAD | journal = Molecular Cell | volume = 22 | issue = 4 | pages = 451–462 | doi = 10.1016/j.molcel.2006.03.036 | doi-access = free | pmid = 16713576 }}</ref>
25 <ref name = "Meyer_1998">{{cite journal | vauthors = Meyer HH, Kondo H, Warren G | date = October 1998 | title = The p47 co-factor regulates the ATPase activity of the membrane fusion protein, p97 | journal = FEBS Letters | volume = 437 | issue = 3 | pages = 255–257 | doi = 10.1016/s0014-5793(98)01232-0 | doi-access = free | pmid = 9824302 | s2cid = 33962985 | bibcode = 1998FEBSL.437..255M }}</ref>
26 <ref name = "Zhang_2015">{{cite journal | vauthors = Zhang X, Gui L, Zhang X, Bulfer SL, Sanghez V, Wong DE, Lee Y, Lehmann L, Lee JS, Shih PY, Lin HJ, Iacovino M, Weihl CC, Arkin MR, Wang Y, Chou TF | title = Altered cofactor regulation with disease-associated p97/VCP mutations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 14 | pages = E1705–14 | date = April 2015 | pmid = 25775548 | pmc = 4394316 | doi = 10.1073/pnas.1418820112 | bibcode = 2015PNAS..112E1705Z | doi-access = free }}</ref>
27 <ref name = "Halawani_2009">{{cite journal | vauthors = Halawani D, LeBlanc AC, Rouiller I, Michnick SW, Servant MJ, Latterich M | date = August 2009 | title = Hereditary inclusion body myopathy-linked p97/VCP mutations in the NH2 domain and the D1 ring modulate p97/VCP ATPase activity and D2 ring conformation | journal = Molecular and Cellular Biology | volume = 29 | issue = 16 | pages = 4484–4494 | doi = 10.1128/MCB.00252-09 | pmc = 2725746 | pmid = 19506019 }}</ref>
28 <ref name = "Weihl_2006">{{cite journal | vauthors = Weihl CC, Dalal S, Pestronk A, Hanson PI | date = January 2006 | title = Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation | journal = Human Molecular Genetics | volume = 15 | issue = 2 | pages = 189–199 | doi = 10.1093/hmg/ddi426 | doi-access = free | pmid = 16321991 }}</ref>
29 <ref name = "Ye_2001">{{cite journal | vauthors = Ye Y, Meyer HH, Rapoport TA | date = December 2001 | title = The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol | journal = Nature | volume = 414 | issue = 6864 | pages = 652–656 | doi = 10.1038/414652a | pmid = 11740563 | bibcode = 2001Natur.414..652Y | s2cid = 23397533 }}</ref>
30 <ref name = "Kondo_1997">{{cite journal | vauthors = Kondo H, Rabouille C, Newman R, Levine TP, Pappin D, Freemont P, Warren G | date = July 1997 | title = p47 is a cofactor for p97-mediated membrane fusion | journal = Nature | volume = 388 | issue = 6637 | pages = 75–78 | doi = 10.1038/40411 | doi-access = free | pmid = 9214505 | bibcode = 1997Natur.388R..75K | s2cid = 32646222 }}</ref>
31 <ref name = "Song_2005">{{cite journal | vauthors = Song EJ, Yim SH, Kim E, Kim NS, Lee KJ | date = March 2005 | title = Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway | journal = Molecular and Cellular Biology | volume = 25 | issue = 6 | pages = 2511–2524 | doi = 10.1128/MCB.25.6.2511-2524.2005 | pmc = 1061599 | pmid = 15743842 }}</ref>
32 <ref name="Qiu_2010">{{cite journal | vauthors = Qiu L, Pashkova N, Walker JR, Winistorfer S, Allali-Hassani A, Akutsu M, Piper R, Dhe-Paganon S | date = January 2010 | title = Structure and function of the PLAA/Ufd3-p97/Cdc48 complex | journal = The Journal of Biological Chemistry | volume = 285 | issue = 1 | pages = 365–372 | doi = 10.1074/jbc.M109.044685 | doi-access = free | pmc = 2804184 | pmid = 19887378 }}</ref>
33 <ref name="Zhao_2007">{{cite journal | vauthors = Zhao G, Zhou X, Wang L, Li G, Schindelin H, Lennarz WJ | date = May 2007 | title = Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 21 | pages = 8785–8790 | doi = 10.1073/pnas.0702966104 | doi-access = free | pmc = 1885580 | pmid = 17496150 | bibcode = 2007PNAS..104.8785Z }}</ref>
34 <ref name="Schaeffer_2014">{{cite journal | vauthors = Schaeffer V, Akutsu M, Olma MH, Gomes LC, Kawasaki M, Dikic I | date = May 2014 | title = Binding of OTULIN to the PUB domain of HOIP controls NF-κB signaling | journal = Molecular Cell | volume = 54 | issue = 3 | pages = 349–361 | doi = 10.1016/j.molcel.2014.03.016 | doi-access = free | pmid = 24726327 }}</ref>
35 <ref name = "Schuberth_2008">{{cite journal | vauthors = Schuberth C, Buchberger A | date = August 2008 | title = UBX domain proteins: major regulators of the AAA ATPase Cdc48/p97 | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 15 | pages = 2360–2371 | doi = 10.1007/s00018-008-8072-8 | doi-access = free | pmc = 11131665 | pmid = 18438607 }}</ref>
36 <ref name = "Stapf_2011">{{cite journal | vauthors = Stapf C, Cartwright E, Bycroft M, Hofmann K, Buchberger A | date = November 2011 | title = The general definition of the p97/valosin-containing protein (VCP)-interacting motif (VIM) delineates a new family of p97 cofactors | journal = The Journal of Biological Chemistry | volume = 286 | issue = 44 | pages = 38670–38678 | doi = 10.1074/jbc.M111.274472 | doi-access = free | pmc = 3207395 | pmid = 21896481 }}</ref>
37 <ref name = "Ballar_2006">{{cite journal | vauthors = Ballar P, Shen Y, Yang H, Fang S | date = November 2006 | title = The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation | journal = The Journal of Biological Chemistry | volume = 281 | issue = 46 | pages = 35359–35368 | doi = 10.1074/jbc.M603355200 | doi-access = free | pmid = 16987818 }}</ref>
38 <ref name = "Ballar_2007">{{cite journal | vauthors = Ballar P, Zhong Y, Nagahama M, Tagaya M, Shen Y, Fang S | date = November 2007 | title = Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum-associated degradation | journal = The Journal of Biological Chemistry | volume = 282 | issue = 47 | pages = 33908–33914 | doi = 10.1074/jbc.M704446200 | doi-access = free | pmid = 17872946 }}</ref>
39 <ref name = "Ye_2004">{{cite journal | vauthors = Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA | date = June 2004 | title = A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol | journal = Nature | volume = 429 | issue = 6994 | pages = 841–847 | doi = 10.1038/nature02656 | pmid = 15215856 | bibcode = 2004Natur.429..841Y | s2cid = 4317750 }}</ref>
40 <ref name = "Hänzelmann_2011">{{cite journal | vauthors = Hänzelmann P, Schindelin H | date = November 2011 | title = The structural and functional basis of the p97/valosin-containing protein (VCP)-interacting motif (VIM): mutually exclusive binding of cofactors to the N-terminal domain of p97 | journal = The Journal of Biological Chemistry | volume = 286 | issue = 44 | pages = 38679–38690 | doi = 10.1074/jbc.M111.274506 | doi-access = free | pmc = 3207442 | pmid = 21914798 }}</ref>
41 <ref name = "Meyer_2000">{{cite journal | vauthors = Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G | date = May 2000 | title = A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways | journal = The EMBO Journal | volume = 19 | issue = 10 | pages = 2181–2192 | doi = 10.1093/emboj/19.10.2181 | pmc = 384367 | pmid = 10811609 }}</ref>
42 <ref name = "Buchberger_2015">{{cite journal | vauthors = Buchberger A, Schindelin H, Hänzelmann P | date = September 2015 | title = Control of p97 function by cofactor binding | journal = FEBS Letters | volume = 589 | issue = 19 Pt A | pages = 2578–2589 | doi = 10.1016/j.febslet.2015.08.028 | doi-access = free | pmid = 26320413 | s2cid = 41082524 | bibcode = 2015FEBSL.589.2578B }}</ref>
43 <ref name = "Meyer_2012">{{cite journal | vauthors = Meyer H, Bug M, Bremer S | date = February 2012 | title = Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system | journal = Nature Cell Biology | volume = 14 | issue = 2 | pages = 117–123 | doi = 10.1038/ncb2407 | pmid = 22298039 | bibcode = 2012NaCB...14..117M | s2cid = 23562362 }}</ref>
44 <ref name = "Christianson_2014">{{cite journal | vauthors = Christianson JC, Ye Y | date = April 2014 | title = Cleaning up in the endoplasmic reticulum: ubiquitin in charge | journal = Nature Structural & Molecular Biology | volume = 21 | issue = 4 | pages = 325–335 | doi = 10.1038/nsmb.2793 | pmc = 9397582 | pmid = 24699081 | s2cid = 43665193 }}</ref>
45 <ref name = "Brandman_2012">{{cite journal | vauthors = Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS | date = November 2012 | title = A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress | journal = Cell | volume = 151 | issue = 5 | pages = 1042–1054 | doi = 10.1016/j.cell.2012.10.044 | pmc = 3534965 | pmid = 23178123 }}</ref>
46 <ref name = "Defenouillère_2013">{{cite journal | vauthors = Defenouillère Q, Yao Y, Mouaikel J, Namane A, Galopier A, Decourty L, Doyen A, Malabat C, Saveanu C, Jacquier A, Fromont-Racine M | date = March 2013 | title = Cdc48-associated complex bound to 60S particles is required for the clearance of aberrant translation products | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 13 | pages = 5046–5051 | doi = 10.1073/pnas.1221724110 | doi-access = free | pmc = 3612664 | pmid = 23479637 | bibcode = 2013PNAS..110.5046D }}</ref>
47 <ref name = "Verma_2013">{{cite journal | vauthors = Verma R, Oania RS, Kolawa NJ, Deshaies RJ | title = Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome | journal = eLife | volume = 2 | article-number = e00308 | date = January 2013 | pmid = 23358411 | pmc = 3552423 | doi = 10.7554/eLife.00308 | doi-access = free }}</ref>
48 <ref name = "Gallagher_2014">{{cite journal | vauthors = Gallagher PS, Clowes Candadai SV, Gardner RG | date = May 2014 | title = The requirement for Cdc48/p97 in nuclear protein quality control degradation depends on the substrate and correlates with substrate insolubility | journal = Journal of Cell Science | volume = 127 | issue = Pt 9 | pages = 1980–1991 | doi = 10.1242/jcs.141838 | pmc = 4004975 | pmid = 24569878 }}</ref>
49 <ref name = "Bug_2012">{{cite journal | vauthors = Bug M, Meyer H | title = Expanding into new markets--VCP/p97 in endocytosis and autophagy | journal = Journal of Structural Biology | volume = 179 | issue = 2 | pages = 78–82 | date = August 2012 | pmid = 22450227 | doi = 10.1016/j.jsb.2012.03.003 }}</ref>
50 <ref name = "Dantuma_2014">{{cite journal | vauthors = Dantuma NP, Acs K, Luijsterburg MS | title = Should I stay or should I go: VCP/p97-mediated chromatin extraction in the DNA damage response | journal = Experimental Cell Research | volume = 329 | issue = 1 | pages = 9–17 | date = November 2014 | pmid = 25169698 | doi = 10.1016/j.yexcr.2014.08.025 }}</ref>
51 <ref name = "Uchiyama_2005">{{cite journal | vauthors = Uchiyama K, Kondo H | date = February 2005 | title = p97/p47-Mediated biogenesis of Golgi and ER | journal = Journal of Biochemistry | volume = 137 | issue = 2 | pages = 115–119 | doi = 10.1093/jb/mvi028 | doi-access = free | pmid = 15749824 | s2cid = 10459261 }}</ref>
52 <ref name = "Fiebiger_2004">{{cite journal | vauthors = Fiebiger E, Hirsch C, Vyas JM, Gordon E, Ploegh HL, Tortorella D | date = April 2004 | title = Dissection of the dislocation pathway for type I membrane proteins with a new small molecule inhibitor, eeyarestatin | journal = Molecular Biology of the Cell | volume = 15 | issue = 4 | pages = 1635–1646 | doi = 10.1091/mbc.E03-07-0506 | pmc = 379262 | pmid = 14767067 }}</ref>
53 <ref name = "Wang_2010">{{cite journal | vauthors = Wang Q, Shinkre BA, Lee JG, Weniger MA, Liu Y, Chen W, Wiestner A, Trenkle WC, Ye Y | title = The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group | journal = PLOS ONE | volume = 5 | issue = 11 | article-number = e15479 | date = November 2010 | pmid = 21124757 | pmc = 2993181 | doi = 10.1371/journal.pone.0015479 | bibcode = 2010PLoSO...515479W | doi-access = free }}</ref>
54 <ref name = "Wang_2009">{{cite journal | vauthors = Wang Q, Mora-Jensen H, Weniger MA, Perez-Galan P, Wolford C, Hai T, Ron D, Chen W, Trenkle W, Wiestner A, Ye Y | date = February 2009 | title = ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 7 | pages = 2200–2205 | doi = 10.1073/pnas.0807611106 | doi-access = free | pmc = 2629785 | pmid = 19164757 | bibcode = 2009PNAS..106.2200W }}</ref>
55 <ref name = "Chou_2013">{{cite journal | vauthors = Chou TF, Li K, Frankowski KJ, Schoenen FJ, Deshaies RJ | title = Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase | journal = ChemMedChem | volume = 8 | issue = 2 | pages = 297–312 | date = February 2013 | pmid = 23316025 | pmc = 3662613 | doi = 10.1002/cmdc.201200520 }}</ref>
56 <ref name = "Chou_2011">{{cite journal | vauthors = Chou TF, Brown SJ, Minond D, Nordin BE, Li K, Jones AC, Chase P, Porubsky PR, Stoltz BM, Schoenen FJ, Patricelli MP, Hodder P, Rosen H, Deshaies RJ | date = March 2011 | title = Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 12 | pages = 4834–4839 | doi = 10.1073/pnas.1015312108 | doi-access = free | pmc = 3064330 | pmid = 21383145 | bibcode = 2011PNAS..108.4834C }}</ref>
57 <ref name = "Magnaghi_2013">{{cite journal | vauthors = Magnaghi P, D'Alessio R, Valsasina B, Avanzi N, Rizzi S, Asa D, Gasparri F, Cozzi L, Cucchi U, Orrenius C, Polucci P, Ballinari D, Perrera C, Leone A, Cervi G, Casale E, Xiao Y, Wong C, Anderson DJ, Galvani A, Donati D, O'Brien T, Jackson PK, Isacchi A | date = September 2013 | title = Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death | journal = Nature Chemical Biology | volume = 9 | issue = 9 | pages = 548–556 | doi = 10.1038/nchembio.1313 | pmid = 23892893 }}</ref>
58 <ref name = "Anderson_2015">{{cite journal | vauthors = Anderson DJ, Le Moigne R, Djakovic S, Kumar B, Rice J, Wong S, Wang J, Yao B, Valle E, Kiss von Soly S, Madriaga A, Soriano F, Menon MK, Wu ZY, Kampmann M, Chen Y, Weissman JS, Aftab BT, Yakes FM, Shawver L, Zhou HJ, Wustrow D, Rolfe M | title = Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis | journal = Cancer Cell | volume = 28 | issue = 5 | pages = 653–665 | date = November 2015 | pmid = 26555175 | pmc = 4941640 | doi = 10.1016/j.ccell.2015.10.002 }}</ref>
}}
== Further reading == {{refbegin|33em}} * {{cite journal | vauthors = Guinto JB, Ritson GP, Taylor JP, Forman MS | title = Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy | journal = Acta Neuropathologica | volume = 114 | issue = 1 | pages = 55–61 | date = July 2007 | pmid = 17457594 | doi = 10.1007/s00401-007-0224-7 | s2cid = 2094590 }} * {{cite journal | vauthors = Dawson SJ, White LA | date = May 1992 | title = Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin | journal = The Journal of Infection | volume = 24 | issue = 3 | pages = 317–320 | doi = 10.1016/S0163-4453(05)80037-4 | pmid = 1602151 }} * {{cite journal | vauthors = Pleasure IT, Black MM, Keen JH | date = September 1993 | title = Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein | journal = Nature | volume = 365 | issue = 6445 | pages = 459–462 | doi = 10.1038/365459a0 | pmid = 8413590 | bibcode = 1993Natur.365..459P | s2cid = 4307576 }} * {{cite journal | vauthors = Germain-Lee EL, Obie C, Valle D | title = NVL: a new member of the AAA family of ATPases localized to the nucleus | journal = Genomics | volume = 44 | issue = 1 | pages = 22–34 | date = August 1997 | pmid = 9286697 | doi = 10.1006/geno.1997.4856 | doi-access = free }} * {{cite journal | vauthors = Hoyle J, Tan KH, Fisher EM | date = October 1997 | title = Mapping the valosin-containing protein (VCP) gene on human chromosome 9 and mouse chromosome 4, and a likely pseudogene on the mouse X chromosome | journal = Mammalian Genome | volume = 8 | issue = 10 | pages = 778–780 | doi = 10.1007/s003359900566 | pmid = 9321476 | s2cid = 563437 }} * {{cite journal | vauthors = Dai RM, Chen E, Longo DL, Gorbea CM, Li CC | date = February 1998 | title = Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3562–3573 | doi = 10.1074/jbc.273.6.3562 | doi-access = free | pmid = 9452483 }} * {{cite journal | vauthors = Rabouille C, Kondo H, Newman R, Hui N, Freemont P, Warren G | date = March 1998 | title = Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro | journal = Cell | volume = 92 | issue = 5 | pages = 603–610 | doi = 10.1016/S0092-8674(00)81128-9 | doi-access = free | pmid = 9506515 | s2cid = 17285800 }} * {{cite journal | vauthors = Zhang SH, Liu J, Kobayashi R, Tonks NK | date = June 1999 | title = Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 17806–17812 | doi = 10.1074/jbc.274.25.17806 | doi-access = free | pmid = 10364224 }} * {{cite journal | vauthors = Zhang H, Wang Q, Kajino K, Greene MI | date = May 2000 | title = VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells | journal = DNA and Cell Biology | volume = 19 | issue = 5 | pages = 253–263 | doi = 10.1089/10445490050021168 | pmid = 10855792 }} * {{cite journal | vauthors = Lavoie C, Chevet E, Roy L, Tonks NK, Fazel A, Posner BI, Paiement J, Bergeron JJ | date = December 2000 | title = Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 25 | pages = 13637–13642 | doi = 10.1073/pnas.240278097 | doi-access = free | pmc = 17628 | pmid = 11087817 | bibcode = 2000PNAS...9713637L }} * {{cite journal | vauthors = Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S | date = December 2001 | title = Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways | journal = Molecular and Cellular Biology | volume = 21 | issue = 23 | pages = 8035–8044 | doi = 10.1128/MCB.21.23.8035-8044.2001 | pmc = 99970 | pmid = 11689694 }} * {{cite journal | vauthors = Yang CS, Weiner H | date = April 2002 | title = Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol | journal = Archives of Biochemistry and Biophysics | volume = 400 | issue = 1 | pages = 105–110 | doi = 10.1006/abbi.2002.2778 | pmid = 11913976 }} * {{cite journal | vauthors = Asai T, Tomita Y, Nakatsuka S, Hoshida Y, Myoui A, Yoshikawa H, Aozasa K | title = VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line | journal = Japanese Journal of Cancer Research | volume = 93 | issue = 3 | pages = 296–304 | date = March 2002 | pmid = 11927012 | pmc = 5926968 | doi = 10.1111/j.1349-7006.2002.tb02172.x }} * {{cite journal | vauthors = Kobayashi T, Tanaka K, Inoue K, Kakizuka A | date = December 2002 | title = Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 49 | pages = 47358–47365 | doi = 10.1074/jbc.M207783200 | doi-access = free | pmid = 12351637 }} * {{cite journal | vauthors = Uchiyama K, Jokitalo E, Kano F, Murata M, Zhang X, Canas B, Newman R, Rabouille C, Pappin D, Freemont P, Kondo H | date = December 2002 | title = VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo | journal = The Journal of Cell Biology | volume = 159 | issue = 5 | pages = 855–866 | doi = 10.1083/jcb.200208112 | pmc = 2173386 | pmid = 12473691 }} {{refend}}
== External links == *[https://www.ncbi.nlm.nih.gov/books/NBK1476/ GeneReviews/NIH/NCBI/UW entry on Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia] * {{PDBe-KB2|P55072|Transitional endoplasmic reticulum ATPase}}
{{PDB Gallery|geneid=7415}}