Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transitional endoplasmic reticulum ATPase

Gene

VCP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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). Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response (PubMed:29804830). 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). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).17 Publications

Caution

It is unclear how it participates in the recruitment of TP53BP1 at DNA damage sites. According to a first report, participates in the recruitment of TP53BP1 by promoting ubiquitination and removal of L3MBTL1 from DNA damage sites (PubMed:22120668). According to a second report, it acts by removing 'Lys-48'-linked ubiquitination from sites of DNA damage (PubMed:22020440).2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei348ATP 11 Publication1
Binding sitei384ATP 11 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi247 – 253ATP 11 Publication7
Nucleotide bindingi521 – 526ATP 2By similarity6

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processAutophagy, DNA damage, DNA repair, Transport, Ubl conjugation pathway
LigandATP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-110320 Translesion Synthesis by POLH
R-HSA-3371511 HSF1 activation
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-5689877 Josephin domain DUBs
R-HSA-5689896 Ovarian tumor domain proteases
R-HSA-6798695 Neutrophil degranulation
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8876725 Protein methylation
SignaLinkiP55072
SIGNORiP55072

Protein family/group databases

MoonDBiP55072 Predicted
TCDBi3.A.16.1.1 the endoplasmic reticular retrotranslocon (er-rt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Transitional endoplasmic reticulum ATPase (EC:3.6.4.61 Publication)
Short name:
TER ATPase
Alternative name(s):
15S Mg(2+)-ATPase p97 subunit
Valosin-containing protein
Short name:
VCP
Gene namesi
Name:VCP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165280.15
HGNCiHGNC:12666 VCP
MIMi601023 gene
neXtProtiNX_P55072

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Involvement in diseasei

Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1)15 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance.
See also OMIM:167320
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03301695R → G in IBMPFD1; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP; abolishes enhancement of K-315 methylation by ASPSCR1; decreased interaction with CAV1 and UBXN6. 4 PublicationsCorresponds to variant dbSNP:rs121909332EnsemblClinVar.1
Natural variantiVAR_076465126I → F in IBMPFD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_033017155R → C in IBMPFD1; also in one patient without evidence of Paget disease of the bone. 2 PublicationsCorresponds to variant dbSNP:rs121909330EnsemblClinVar.1
Natural variantiVAR_078910155R → L in IBMPFD1. 1 Publication1
Natural variantiVAR_033019155R → P in IBMPFD1. 1 PublicationCorresponds to variant dbSNP:rs121909329EnsemblClinVar.1
Natural variantiVAR_076466155R → S in IBMPFD1; impaired autophagic function. 1 Publication1
Natural variantiVAR_033020159R → H in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1. 1 PublicationCorresponds to variant dbSNP:rs121909335EnsemblClinVar.1
Natural variantiVAR_076468198L → W in IBMPFD1; increased ATPase activity; impaired autophagic function. 4 Publications1
Natural variantiVAR_033022232A → E in IBMPFD1; increased ATPase activity; no defect in ubiquitin-dependent protein degradation by the proteasome; impaired autophagic function; defect in maturation of ubiquitin-containing autophagosomes; decreased interaction with CAV1 and UBXN6. 6 PublicationsCorresponds to variant dbSNP:rs121909331EnsemblClinVar.1
Natural variantiVAR_078911387N → H in IBMPFD1; unknown pathological significance. 1 Publication1
Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS14 may develop frontotemporal dementia.
See also OMIM:613954
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065910159R → G in ALS14. 2 PublicationsCorresponds to variant dbSNP:rs387906789EnsemblClinVar.1
Natural variantiVAR_065911592D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 PublicationCorresponds to variant dbSNP:rs387906790EnsemblClinVar.1
Charcot-Marie-Tooth disease 2Y (CMT2Y)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
See also OMIM:616687
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07646497G → E in CMT2Y; increased ATPase activity. 1 PublicationCorresponds to variant dbSNP:rs864309502EnsemblClinVar.1
Natural variantiVAR_076467185E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 PublicationCorresponds to variant dbSNP:rs864309501EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52 – 55FRGD → ARGA: Abolishes interaction with NPLOC4; when associated with A-110. 1 Publication4
Mutagenesisi53R → A: Minor effect on affinity for ATP and ADP. 1 Publication1
Mutagenesisi86R → A: Strongly increased affinity for ATP. Strongly reduced affinity for ADP. 1 Publication1
Mutagenesisi110Y → A: Abolishes interaction with NPLOC4; when associated with 52-A--A-55. 1 Publication1
Mutagenesisi251K → Q: Impairs ERAD degradation of HMGCR and does not inhibit interaction with RHBDD1; when associated with Q-524. 2 Publications1
Mutagenesisi305E → Q: Defect in ubiquitin-dependent protein degradation by the proteasome; when associated with Q-578. 2 Publications1
Mutagenesisi312K → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi313R → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi314E → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi314Missing : Strongly impairs methylation by VCPKMT. 1 Publication1
Mutagenesisi315K → L, Q or R: Abolishes methylation by VCPKMT. 2 Publications1
Mutagenesisi316T → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi317H → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi318G → A: Does not affect methylation by VCPKMT. 1 Publication1
Mutagenesisi524K → A: Impairs catalytic activity of RNF19A toward SOD1 mutant. Does not inhibit interaction with RHBDD1; when associated with A-251. 3 Publications1
Mutagenesisi524K → Q: Impairs ERAD degradation of HMGCR; when associated with Q-251. 3 Publications1
Mutagenesisi578E → Q: Does not inhibit interaction with RHBDD1. Increased interaction with CAV1 and UBXN6. Impaired autophagic function. Defect in ubiquitin-dependent protein degradation by the proteasome; when associated with Q-305. Increases interaction with ZFAND1 in an arsenite-dependent manner. 5 Publications1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi7415
GeneReviewsiVCP
MalaCardsiVCP
MIMi167320 phenotype
613954 phenotype
616687 phenotype
OpenTargetsiENSG00000165280
Orphaneti329478 Adult-onset distal myopathy due to VCP mutation
803 Amyotrophic lateral sclerosis
435387 Autosomal dominant Charcot-Marie-Tooth disease type 2Y
275864 Behavioral variant of frontotemporal dementia
275872 Frontotemporal dementia with motor neuron disease
52430 Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
100070 Progressive non-fluent aphasia
329475 Spastic paraplegia-Paget disease of bone syndrome
PharmGKBiPA37289

Chemistry databases

ChEMBLiCHEMBL1075145
DrugBankiDB04395 Phosphoaminophosphonic Acid-Adenylate Ester

Polymorphism and mutation databases

BioMutaiVCP
DMDMi6094447

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000845722 – 806Transitional endoplasmic reticulum ATPaseAdd BLAST805

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei3PhosphoserineCombined sources1
Modified residuei7PhosphoserineCombined sources1
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei13PhosphoserineCombined sources1
Cross-linki18Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei37PhosphoserineCombined sources1
Modified residuei315N6,N6,N6-trimethyllysine; by VCPKMT2 Publications1
Modified residuei436PhosphothreonineCombined sources1
Modified residuei462PhosphoserineCombined sources1
Modified residuei502N6-acetyllysineBy similarity1
Modified residuei505N6-acetyllysineBy similarity1
Modified residuei668N6-acetyllysine; alternateBy similarity1
Modified residuei668N6-succinyllysine; alternateBy similarity1
Modified residuei702PhosphoserineCombined sources1
Modified residuei754N6-acetyllysineBy similarity1
Modified residuei770PhosphoserineCombined sources1
Modified residuei775PhosphoserineCombined sources1
Modified residuei787PhosphoserineCombined sources1
Modified residuei805PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells.By similarity
ISGylated.1 Publication
Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP55072
PaxDbiP55072
PeptideAtlasiP55072
PRIDEiP55072
ProteomicsDBi56776
TopDownProteomicsiP55072

2D gel databases

DOSAC-COBS-2DPAGEiP55072
OGPiP55072
REPRODUCTION-2DPAGEiIPI00022774
P55072

PTM databases

CarbonylDBiP55072
iPTMnetiP55072
PhosphoSitePlusiP55072
SwissPalmiP55072

Expressioni

Gene expression databases

BgeeiENSG00000165280 Expressed in 230 organ(s), highest expression level in adrenal tissue
CleanExiHS_VCP
ExpressionAtlasiP55072 baseline and differential
GenevisibleiP55072 HS

Organism-specific databases

HPAiCAB005593
HPA012728
HPA012814

Interactioni

Subunit structurei

Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1, binding to this heterodimer inhibits Golgi-membrane fusion (PubMed:26471729). Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1 and VCP. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with SELENOS and SYVN1, as well as with DERL1, DERL2 and DERL3; which probably transfer misfolded proteins from the ER to VCP. Interacts with SVIP. Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Directly interacts with UBXN4 and RNF19A. Interacts with CASR. Interacts with UBE4B and YOD1. Interacts with clathrin. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with RHBDD1 (via C-terminal domain). Interacts with SPRTN; leading to recruitment to stalled replication forks (PubMed:23042607, PubMed:23042605). Interacts with WASHC5. Interacts with UBOX5. Interacts (via N-terminus) with UBXN7, UBXN8, and probably several other UBX domain-containing proteins (via UBX domains); the interactions are mutually exclusive with VIM-dependent interactions such as those with AMFR and SELENOS. Forms a complex with UBQLN1 and UBXN4. Interacts (via the PIM motif) with RNF31 (via the PUB domain) (PubMed:24726327). Interacts with DDX58/RIG-I and RNF125; 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). Interacts with BAG6 (PubMed:21636303). Interacts with UBXN10 (PubMed:26389662). Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (PubMed:19174149, PubMed:19275885). Forms a ternary complex with CAV1 and UBXN6 (PubMed:21822278, PubMed:18656546, PubMed:19174149). Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (PubMed:27753622). Interacts with ANKZF1 (PubMed:28302725). Interacts with ubiquitin-binding protein FAF1 (PubMed:26842564). Interacts with ZFAND2B (via VIM motif); the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (PubMed:29804830).By similarity41 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113258, 625 interactors
ComplexPortaliCPX-137 VCP-NPL4-UFD1 AAA ATPase complex
CPX-262 NSFL1C-VCP complex
CORUMiP55072
DIPiDIP-33543N
IntActiP55072, 109 interactors
MINTiP55072
STRINGi9606.ENSP00000351777

Chemistry databases

BindingDBiP55072

Structurei

Secondary structure

1806
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP55072
SMRiP55072
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55072

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni797 – 806Interaction with UBXN61 Publication10

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi802 – 806PIM motif1 Publication5

Domaini

The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31.1 Publication

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Phylogenomic databases

eggNOGiKOG0730 Eukaryota
COG0464 LUCA
GeneTreeiENSGT00900000141071
HOGENOMiHOG000223224
HOVERGENiHBG001226
InParanoidiP55072
KOiK13525
OMAiPIDDTTE
OrthoDBiEOG091G024K
PhylomeDBiP55072
TreeFamiTF300542

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR005938 AAA_ATPase_CDC48
IPR009010 Asp_de-COase-like_dom_sf
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR004201 Cdc48_dom2
IPR029067 CDC48_domain_2-like_sf
IPR003338 CDC4_N-term_subdom
IPR027417 P-loop_NTPase
IPR015415 Vps4_C
PfamiView protein in Pfam
PF00004 AAA, 2 hits
PF02933 CDC48_2, 1 hit
PF02359 CDC48_N, 1 hit
PF09336 Vps4_C, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SM01072 CDC48_2, 1 hit
SM01073 CDC48_N, 1 hit
SUPFAMiSSF50692 SSF50692, 1 hit
SSF52540 SSF52540, 2 hits
SSF54585 SSF54585, 1 hit
TIGRFAMsiTIGR01243 CDC48, 1 hit
PROSITEiView protein in PROSITE
PS00674 AAA, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P55072-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ
60 70 80 90 100
LFRGDTVLLK GKKRREAVCI VLSDDTCSDE KIRMNRVVRN NLRVRLGDVI
110 120 130 140 150
SIQPCPDVKY GKRIHVLPID DTVEGITGNL FEVYLKPYFL EAYRPIRKGD
160 170 180 190 200
IFLVRGGMRA VEFKVVETDP SPYCIVAPDT VIHCEGEPIK REDEEESLNE
210 220 230 240 250
VGYDDIGGCR KQLAQIKEMV ELPLRHPALF KAIGVKPPRG ILLYGPPGTG
260 270 280 290 300
KTLIARAVAN ETGAFFFLIN GPEIMSKLAG ESESNLRKAF EEAEKNAPAI
310 320 330 340 350
IFIDELDAIA PKREKTHGEV ERRIVSQLLT LMDGLKQRAH VIVMAATNRP
360 370 380 390 400
NSIDPALRRF GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA
410 420 430 440 450
NETHGHVGAD LAALCSEAAL QAIRKKMDLI DLEDETIDAE VMNSLAVTMD
460 470 480 490 500
DFRWALSQSN PSALRETVVE VPQVTWEDIG GLEDVKRELQ ELVQYPVEHP
510 520 530 540 550
DKFLKFGMTP SKGVLFYGPP GCGKTLLAKA IANECQANFI SIKGPELLTM
560 570 580 590 600
WFGESEANVR EIFDKARQAA PCVLFFDELD SIAKARGGNI GDGGGAADRV
610 620 630 640 650
INQILTEMDG MSTKKNVFII GATNRPDIID PAILRPGRLD QLIYIPLPDE
660 670 680 690 700
KSRVAILKAN LRKSPVAKDV DLEFLAKMTN GFSGADLTEI CQRACKLAIR
710 720 730 740 750
ESIESEIRRE RERQTNPSAM EVEEDDPVPE IRRDHFEEAM RFARRSVSDN
760 770 780 790 800
DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG AGPSQGSGGG TGGSVYTEDN

DDDLYG
Length:806
Mass (Da):89,322
Last modified:January 23, 2007 - v4
Checksum:i501B721D3A77BA8A
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9IZA5C9IZA5_HUMAN
Transitional endoplasmic reticulum ...
VCP
160Annotation score:
C9JUP7C9JUP7_HUMAN
Transitional endoplasmic reticulum ...
VCP
115Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti169D → H in AAI21795 (PubMed:15489334).Curated1
Sequence conflicti312K → I in BAG35235 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03301695R → G in IBMPFD1; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP; abolishes enhancement of K-315 methylation by ASPSCR1; decreased interaction with CAV1 and UBXN6. 4 PublicationsCorresponds to variant dbSNP:rs121909332EnsemblClinVar.1
Natural variantiVAR_07646497G → E in CMT2Y; increased ATPase activity. 1 PublicationCorresponds to variant dbSNP:rs864309502EnsemblClinVar.1
Natural variantiVAR_076465126I → F in IBMPFD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_033017155R → C in IBMPFD1; also in one patient without evidence of Paget disease of the bone. 2 PublicationsCorresponds to variant dbSNP:rs121909330EnsemblClinVar.1
Natural variantiVAR_033018155R → H in ALS14 and IBMPFD1; ALS14 patients do not manifest frontotemporal dementia; properly assembles into a hexameric structure; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP; shows normal ATPase activity according to PubMed:16321991 while according to PubMed:25878907 and PubMed:25125609 shows increased ATPase activity; no defect in ubiquitin-dependent protein degradation by the proteasome; impaired autophagic function; defective maturation of ubiquitin-containing autophagosomes; decreased interaction with CAV1 and UBXN6; decreased endosome to lysosome transport via multivesicular body sorting pathway of CAV1; decreases the arsenite-induced stress granules (SGs) clearance process. 11 PublicationsCorresponds to variant dbSNP:rs121909329EnsemblClinVar.1
Natural variantiVAR_078910155R → L in IBMPFD1. 1 Publication1
Natural variantiVAR_033019155R → P in IBMPFD1. 1 PublicationCorresponds to variant dbSNP:rs121909329EnsemblClinVar.1
Natural variantiVAR_076466155R → S in IBMPFD1; impaired autophagic function. 1 Publication1
Natural variantiVAR_065910159R → G in ALS14. 2 PublicationsCorresponds to variant dbSNP:rs387906789EnsemblClinVar.1
Natural variantiVAR_033020159R → H in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1. 1 PublicationCorresponds to variant dbSNP:rs121909335EnsemblClinVar.1
Natural variantiVAR_076467185E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 PublicationCorresponds to variant dbSNP:rs864309501EnsemblClinVar.1
Natural variantiVAR_033021191R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 PublicationsCorresponds to variant dbSNP:rs121909334EnsemblClinVar.1
Natural variantiVAR_076468198L → W in IBMPFD1; increased ATPase activity; impaired autophagic function. 4 Publications1
Natural variantiVAR_033022232A → E in IBMPFD1; increased ATPase activity; no defect in ubiquitin-dependent protein degradation by the proteasome; impaired autophagic function; defect in maturation of ubiquitin-containing autophagosomes; decreased interaction with CAV1 and UBXN6. 6 PublicationsCorresponds to variant dbSNP:rs121909331EnsemblClinVar.1
Natural variantiVAR_078911387N → H in IBMPFD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_065911592D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 PublicationCorresponds to variant dbSNP:rs387906790EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004472 Genomic DNA Translation: AAC07984.1
AF100752 mRNA Translation: AAD43016.1
AK312310 mRNA Translation: BAG35235.1
AL353795 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58404.1
BC110913 mRNA Translation: AAI10914.1
BC121794 mRNA Translation: AAI21795.1
Z70768 mRNA Translation: CAA94809.1
CCDSiCCDS6573.1
PIRiT02243
RefSeqiNP_009057.1, NM_007126.3
UniGeneiHs.529782

Genome annotation databases

EnsembliENST00000358901; ENSP00000351777; ENSG00000165280
GeneIDi7415
KEGGihsa:7415

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004472 Genomic DNA Translation: AAC07984.1
AF100752 mRNA Translation: AAD43016.1
AK312310 mRNA Translation: BAG35235.1
AL353795 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58404.1
BC110913 mRNA Translation: AAI10914.1
BC121794 mRNA Translation: AAI21795.1
Z70768 mRNA Translation: CAA94809.1
CCDSiCCDS6573.1
PIRiT02243
RefSeqiNP_009057.1, NM_007126.3
UniGeneiHs.529782

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EBBX-ray1.90E/F/G/H797-806[»]
3HU1X-ray2.81A/B/C/D/E/F1-481[»]
3HU2X-ray2.85A/B/C/D/E/F1-481[»]
3HU3X-ray2.20A/B1-481[»]
3QC8X-ray2.20A21-196[»]
3QQ7X-ray2.65A2-187[»]
3QQ8X-ray2.00A2-187[»]
3QWZX-ray2.00A1-208[»]
3TIWX-ray1.80A/B1-187[»]
4KDIX-ray1.86A/B21-196[»]
4KDLX-ray1.81A21-196[»]
4KLNX-ray2.62A/B/C/D/E/F1-481[»]
4KO8X-ray1.98A/B1-481[»]
4KODX-ray2.96A/B/C/D/E/F/G/H/I/J/K/L1-481[»]
4P0AX-ray2.30B/D797-806[»]
5B6CX-ray1.55A21-191[»]
5C18X-ray3.30A/B/C/D/E/F2-806[»]
5C19X-ray4.20A/B/C/D/E/F2-806[»]
5C1AX-ray3.80A/B/C/D/E/F/G/H/I/J/K/L2-806[»]
5C1BX-ray3.08A/B/C/D/E/F2-806[»]
5DYGX-ray2.20A1-460[»]
5DYIX-ray3.71A/B/C/D/E/F/G/H/I/J/K/L1-481[»]
5EPPX-ray1.88A21-199[»]
5FTJelectron microscopy2.30A/B/C/D/E/F1-806[»]
5FTKelectron microscopy2.40A/B/C/D/E/F1-806[»]
5FTLelectron microscopy3.30A/B/C/D/E/F1-806[»]
5FTMelectron microscopy3.20A/B/C/D/E/F1-806[»]
5FTNelectron microscopy3.30A/B/C/D/E/F1-806[»]
5GLFX-ray2.25A/C/E/G21-199[»]
5IFSX-ray2.46B/D1-481[»]
5IFWX-ray3.40B2-806[»]
5KIWX-ray3.41A/B1-460[»]
5KIYX-ray2.79A1-460[»]
5X4LX-ray2.40A/B23-196[»]
ProteinModelPortaliP55072
SMRiP55072
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113258, 625 interactors
ComplexPortaliCPX-137 VCP-NPL4-UFD1 AAA ATPase complex
CPX-262 NSFL1C-VCP complex
CORUMiP55072
DIPiDIP-33543N
IntActiP55072, 109 interactors
MINTiP55072
STRINGi9606.ENSP00000351777

Chemistry databases

BindingDBiP55072
ChEMBLiCHEMBL1075145
DrugBankiDB04395 Phosphoaminophosphonic Acid-Adenylate Ester

Protein family/group databases

MoonDBiP55072 Predicted
TCDBi3.A.16.1.1 the endoplasmic reticular retrotranslocon (er-rt) family

PTM databases

CarbonylDBiP55072
iPTMnetiP55072
PhosphoSitePlusiP55072
SwissPalmiP55072

Polymorphism and mutation databases

BioMutaiVCP
DMDMi6094447

2D gel databases

DOSAC-COBS-2DPAGEiP55072
OGPiP55072
REPRODUCTION-2DPAGEiIPI00022774
P55072

Proteomic databases

EPDiP55072
PaxDbiP55072
PeptideAtlasiP55072
PRIDEiP55072
ProteomicsDBi56776
TopDownProteomicsiP55072

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358901; ENSP00000351777; ENSG00000165280
GeneIDi7415
KEGGihsa:7415

Organism-specific databases

CTDi7415
DisGeNETi7415
EuPathDBiHostDB:ENSG00000165280.15
GeneCardsiVCP
GeneReviewsiVCP
HGNCiHGNC:12666 VCP
HPAiCAB005593
HPA012728
HPA012814
MalaCardsiVCP
MIMi167320 phenotype
601023 gene
613954 phenotype
616687 phenotype
neXtProtiNX_P55072
OpenTargetsiENSG00000165280
Orphaneti329478 Adult-onset distal myopathy due to VCP mutation
803 Amyotrophic lateral sclerosis
435387 Autosomal dominant Charcot-Marie-Tooth disease type 2Y
275864 Behavioral variant of frontotemporal dementia
275872 Frontotemporal dementia with motor neuron disease
52430 Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
100070 Progressive non-fluent aphasia
329475 Spastic paraplegia-Paget disease of bone syndrome
PharmGKBiPA37289
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0730 Eukaryota
COG0464 LUCA
GeneTreeiENSGT00900000141071
HOGENOMiHOG000223224
HOVERGENiHBG001226
InParanoidiP55072
KOiK13525
OMAiPIDDTTE
OrthoDBiEOG091G024K
PhylomeDBiP55072
TreeFamiTF300542

Enzyme and pathway databases

ReactomeiR-HSA-110320 Translesion Synthesis by POLH
R-HSA-3371511 HSF1 activation
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-5689877 Josephin domain DUBs
R-HSA-5689896 Ovarian tumor domain proteases
R-HSA-6798695 Neutrophil degranulation
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8876725 Protein methylation
SignaLinkiP55072
SIGNORiP55072

Miscellaneous databases

ChiTaRSiVCP human
EvolutionaryTraceiP55072
GeneWikiiValosin-containing_protein
GenomeRNAii7415
PROiPR:P55072
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165280 Expressed in 230 organ(s), highest expression level in adrenal tissue
CleanExiHS_VCP
ExpressionAtlasiP55072 baseline and differential
GenevisibleiP55072 HS

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR005938 AAA_ATPase_CDC48
IPR009010 Asp_de-COase-like_dom_sf
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR004201 Cdc48_dom2
IPR029067 CDC48_domain_2-like_sf
IPR003338 CDC4_N-term_subdom
IPR027417 P-loop_NTPase
IPR015415 Vps4_C
PfamiView protein in Pfam
PF00004 AAA, 2 hits
PF02933 CDC48_2, 1 hit
PF02359 CDC48_N, 1 hit
PF09336 Vps4_C, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SM01072 CDC48_2, 1 hit
SM01073 CDC48_N, 1 hit
SUPFAMiSSF50692 SSF50692, 1 hit
SSF52540 SSF52540, 2 hits
SSF54585 SSF54585, 1 hit
TIGRFAMsiTIGR01243 CDC48, 1 hit
PROSITEiView protein in PROSITE
PS00674 AAA, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTERA_HUMAN
AccessioniPrimary (citable) accession number: P55072
Secondary accession number(s): B2R5T8
, Q0V924, Q2TAI5, Q969G7, Q9UCD5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 206 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again