Protein: P55072

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P55072 (Uniprot) TERA_HUMAN VCP Transitional endoplasmic reticulum ATPase human No
Uniprot: Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042607, PubMed:23042605). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with DDX58/RIG-I: interaction takes place when DDX58/RIG-I is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0010646 regulation of cell communication 284 GO:0006725 cellular aromatic compound metabolic process 57 4.64e-30 1.07e-07
GO:0033036 macromolecule localization 517 GO:0006725 cellular aromatic compound metabolic process 57 1.29e-20 6.46e-74
GO:0033036 macromolecule localization 517 GO:0043170 macromolecule metabolic process 531 2.48e-08 1.95e-27
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
57 GO:0006139 nucleobase-containing compound metabolic process
177 GO:0044267 cellular protein metabolic process
284 GO:0009966 regulation of signal transduction
517 GO:0008104 protein localization
517 GO:0019538 protein metabolic process
531 GO:0019538 protein metabolic process
555 GO:0006464 cellular protein modification process
555 GO:0060255 regulation of macromolecule metabolic process
555 GO:0007165 signal transduction
560 GO:0006464 cellular protein modification process
560 GO:0060255 regulation of macromolecule metabolic process
560 GO:0007165 signal transduction
652 GO:0044267 cellular protein metabolic process
652 GO:0060255 regulation of macromolecule metabolic process
836 GO:0007165 signal transduction
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
57 GO:0005634 nucleus
177 GO:0005634 nucleus
256 GO:0043232 intracellular non-membrane-bounded organelle
256 GO:0005634 nucleus
284 GO:0005829 cytosol
284 GO:0005886 plasma membrane
517 GO:0005829 cytosol
517 GO:0012505 endomembrane system
517 GO:0031982 vesicle
555 GO:0005634 nucleus
560 GO:0005829 cytosol
652 GO:0005829 cytosol
652 GO:0005634 nucleus
652 GO:0031982 vesicle
836 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0006281 DNA repair NAS
GO:0006302 double-strand break repair IDA
GO:0006457 protein folding TAS
GO:0006479 protein methylation TAS
GO:0006734 NADH metabolic process IMP
GO:0006888 ER to Golgi vesicle-mediated transport IEA
GO:0006914 autophagy IMP
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process ISS
GO:0006974 cellular response to DNA damage stimulus IDA
GO:0010498 proteasomal protein catabolic process IMP
GO:0010918 positive regulation of mitochondrial membrane potential IMP
GO:0016236 macroautophagy IMP
GO:0016567 protein ubiquitination TAS
GO:0016579 protein deubiquitination TAS
GO:0018279 protein N-linked glycosylation via asparagine IMP
GO:0019079 viral genome replication IMP
GO:0019985 translesion synthesis IMP
GO:0030433 ubiquitin-dependent ERAD pathway IMP
GO:0030968 endoplasmic reticulum unfolded protein response TAS
GO:0030970 retrograde protein transport, ER to cytosol IMP
GO:0031334 positive regulation of protein complex assembly IDA
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
GO:0032510 endosome to lysosome transport via multivesicular body sorting pathway IMP
GO:0034214 protein hexamerization IEA
GO:0036503 ERAD pathway IDA
GO:0042981 regulation of apoptotic process TAS
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process IMP
GO:0043312 neutrophil degranulation TAS
GO:0045184 establishment of protein localization TAS
GO:0045732 positive regulation of protein catabolic process IDA
GO:0046034 ATP metabolic process IEA
GO:0051260 protein homooligomerization IEA
GO:0055085 transmembrane transport TAS
GO:0061857 endoplasmic reticulum stress-induced pre-emptive quality control IMP
GO:0070842 aggresome assembly IEA
GO:0070987 error-free translesion synthesis TAS
GO:0071712 ER-associated misfolded protein catabolic process IMP
GO:0072389 flavin adenine dinucleotide catabolic process IMP
GO:0097352 autophagosome maturation IMP
GO:1903006 positive regulation of protein K63-linked deubiquitination IDA
GO:1903007 positive regulation of Lys63-specific deubiquitinase activity IDA
GO:1903715 regulation of aerobic respiration IMP
GO:1903862 positive regulation of oxidative phosphorylation IMP
GO:2000158 positive regulation of ubiquitin-specific protease activity IEA
GO:2001171 positive regulation of ATP biosynthetic process IMP
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000502 proteasome complex IDA
GO:0005576 extracellular region TAS
GO:0005634 nucleus IDA
GO:0005654 nucleoplasm TAS
GO:0005737 cytoplasm IDA
GO:0005783 endoplasmic reticulum IDA
GO:0005789 endoplasmic reticulum membrane TAS
GO:0005811 lipid droplet IDA
GO:0005829 cytosol TAS
GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex TAS
GO:0034774 secretory granule lumen TAS
GO:0035578 azurophil granule lumen TAS
GO:0035861 site of double-strand break IDA
GO:0036513 Derlin-1 retrotranslocation complex IDA
GO:0043209 myelin sheath IEA
GO:0043231 intracellular membrane-bounded organelle ISS
GO:0043234 protein complex IDA
GO:0048471 perinuclear region of cytoplasm IDA
GO:0070062 extracellular exosome IDA
GO:1904813 ficolin-1-rich granule lumen TAS
GO:1904949 ATPase complex IEA
GO:1990730 VCP-NSFL1C complex ISS
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005576 extracellular region GO:0005634 nucleus 4.48e-91 1.28e-107
GO:0005576 extracellular region GO:0005654 nucleoplasm 6.62e-72 7.68e-98
GO:0005576 extracellular region GO:0043231 intracellular membrane-bounded organelle 1.18e-59 7.46e-19
GO:0005634 nucleus GO:0005783 endoplasmic reticulum 8.26e-33 3.22e-89
GO:0005634 nucleus GO:0005789 endoplasmic reticulum membrane 1.61e-25 3.10e-56
GO:0005634 nucleus GO:0070062 extracellular exosome 6.30e-13 4.54e-26
GO:0005654 nucleoplasm GO:0005783 endoplasmic reticulum 1.84e-53 1.21e-118
GO:0005654 nucleoplasm GO:0005789 endoplasmic reticulum membrane 1.09e-31 5.14e-59
GO:0005654 nucleoplasm GO:0070062 extracellular exosome 3.37e-20 1.23e-35
GO:0005789 endoplasmic reticulum membrane GO:0005829 cytosol 4.27e-12 7.53e-04
PMID Article Title
8413590 Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein.
10931946 Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.
12665801 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
15034582 Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
15164053 DNA sequence and analysis of human chromosome 9.
15215856 A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.
15362974 A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs.
15456787 Physical and functional interaction between dorfin and valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15732117 Mutant valosin-containing protein causes a novel type of frontotemporal dementia.
16139798 Proteomic identification of proteins conjugated to ISG15 in mouse and human cells.
16168377 Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase.
16186509 Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane.
16186510 Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane.
16247064 Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene.
16289116 The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway.
16321991 Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation.
16449189 Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.
16513638 Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin.
16968747 Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated protein degradation.
17314412 The RBCC gene RFP2 (Leu5) encodes a novel transmembrane E3 ubiquitin ligase involved in ERAD.
17525332 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
17935506 Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.
18022694 Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system.
18656546 Ubxd1 is a novel co-factor of the human p97 ATPase.
18675248 Ubiquitin ligase Kf-1 is involved in the endoplasmic reticulum-associated degradation pathway.
18691976 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
19174149 UBXD1 binds p97 through two independent binding sites.
19275885 UBXD1 is a VCP-interacting protein that is involved in ER-associated degradation.
19369195 Large-scale proteomics analysis of the human kinome.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19818707 The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.
19822669 Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD.
19887378 Structure and function of the PLAA/Ufd3-p97/Cdc48 complex.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20104022 VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD.
20335036 Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findings.
20512113 A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants.
20833645 Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.
21118995 The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover.
21145000 Exome sequencing reveals VCP mutations as a cause of familial ALS.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21636303 A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation.
21822278 Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations.
21914798 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.
21949850 The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.
22020440 The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks.
22120668 The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks.
22223895 Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.
22537386 UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1alpha accumulation.
22607976 STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein.
22795130 Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins.
22902628 Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis.
22948820 Lysine methylation of VCP by a member of a novel human protein methyltransferase family.
23042605 DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks.
23042607 DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23335559 Ubiquitination of the N-terminal region of caveolin-1 regulates endosomal sorting by the VCP/p97 AAA-ATPase.
23349634 A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24726327 Binding of OTULIN to the PUB domain of HOIP controls NF-kappaB signaling.
25125609 A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.
25878907 Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation.
25944712 N-terminome analysis of the human mitochondrial proteome.
26389662 Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.
26471729 A non-canonical role of the p97 complex in RIG-I antiviral signaling.
26565908 Pre-emptive quality control protects the ER from protein overload via the proximity of ERAD components and SRP.
27209344 Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions in a case of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia with a novel mutation in the valosin-containing protein gene.
27753622 VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.
28112733 Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
28302725 Ankyrin repeat and zinc-finger domain-containing 1 mutations are associated with infantile-onset inflammatory bowel disease.
OMIM ID Disease Name
167320 Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1
613954 Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia
616687 Charcot-Marie-Tooth disease 2Y
Domain Name Domain ID Source
CDC4_N-term_subdom IPR003338 InterPro
AAA+_ATPase IPR003593 InterPro
ATPase_AAA_core IPR003959 InterPro
ATPase_AAA_CS IPR003960 InterPro
Cdc48_dom2 IPR004201 InterPro
AAA_ATPase_CDC48 IPR005938 InterPro
Asp_de-COase-like_dom_sf IPR009010 InterPro
Vps4_C IPR015415 InterPro
P-loop_NTPase IPR027417 InterPro
CDC48_domain_2-like_sf IPR029067 InterPro
AAA PF00004 Pfam
CDC48_N PF02359 Pfam
CDC48_2 PF02933 Pfam
Vps4_C PF09336 Pfam
AAA PS00674 PROSITE
AAA SM00382 SMART
CDC48_2 SM01072 SMART
CDC48_N SM01073 SMART
SSF50692 SSF50692 SUPFAM
SSF52540 SSF52540 SUPFAM
SSF54585 SSF54585 SUPFAM
T02243 T02243 PIR
CDC48 TIGR01243 TIGRFAMs