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Protein

Transitional endoplasmic reticulum ATPase

Gene

VCP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 UFD1L, 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-UFD1L-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. 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. 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. Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022).By similarity9 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei348ATP1 Publication1
Binding sitei384ATP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi247 – 253ATP1 Publication7
Nucleotide bindingi521 – 526ATPBy similarity6

GO - Molecular functioni

  • ADP binding Source: Ensembl
  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • deubiquitinase activator activity Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • lipid binding Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB
  • polyubiquitin binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • protein phosphatase binding Source: BHF-UCL
  • ubiquitin-like protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • aggresome assembly Source: Ensembl
  • ATP metabolic process Source: Ensembl
  • autophagosome maturation Source: UniProtKB
  • autophagy Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB
  • double-strand break repair Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ERAD pathway Source: UniProtKB
  • ER-associated misfolded protein catabolic process Source: ParkinsonsUK-UCL
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • error-free translesion synthesis Source: Reactome
  • ER to Golgi vesicle-mediated transport Source: Ensembl
  • establishment of protein localization Source: UniProtKB
  • flavin adenine dinucleotide catabolic process Source: ParkinsonsUK-UCL
  • NADH metabolic process Source: ParkinsonsUK-UCL
  • positive regulation of ATP biosynthetic process Source: ParkinsonsUK-UCL
  • positive regulation of Lys63-specific deubiquitinase activity Source: ParkinsonsUK-UCL
  • positive regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL
  • positive regulation of oxidative phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • positive regulation of protein catabolic process Source: BHF-UCL
  • positive regulation of protein complex assembly Source: BHF-UCL
  • positive regulation of protein K63-linked deubiquitination Source: ParkinsonsUK-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein hexamerization Source: Ensembl
  • protein homooligomerization Source: Ensembl
  • protein N-linked glycosylation via asparagine Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of aerobic respiration Source: ParkinsonsUK-UCL
  • regulation of apoptotic process Source: UniProtKB
  • retrograde protein transport, ER to cytosol Source: UniProtKB
  • translesion synthesis Source: UniProtKB
  • viral genome replication Source: CACAO
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Autophagy, DNA damage, DNA repair, Transport, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165280-MONOMER.
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.
SignaLinkiP55072.
SIGNORiP55072.

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Transitional endoplasmic reticulum ATPase (EC:3.6.4.6)
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

HGNCiHGNC:12666. VCP.

Subcellular locationi

  • Cytoplasmcytosol
  • Endoplasmic reticulum
  • Nucleus

  • Note: Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients. Present in the Lewy bodies specifically found in neurons from Parkinson disease patients. Recruited to the cytoplasmic surface of the endoplasmic reticulum via interaction with AMFR/gp78. Following DNA double-strand breaks, recruited to the sites of damage. Recruited to stalled replication forks via interaction with SPRTN.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB
  • Derlin-1 retrotranslocation complex Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: UniProtKB
  • lipid particle Source: MGI
  • myelin sheath Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
  • proteasome complex Source: BHF-UCL
  • site of double-strand break Source: UniProtKB
  • VCP-NPL4-UFD1 AAA ATPase complex Source: ParkinsonsUK-UCL
  • VCP-NSFL1C complex Source: ParkinsonsUK-UCL
Complete GO annotation...

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)7 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. 3 PublicationsCorresponds to variant rs121909332dbSNPEnsembl.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 rs121909330dbSNPEnsembl.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. 8 PublicationsCorresponds to variant rs121909329dbSNPEnsembl.1
Natural variantiVAR_033019155R → P in IBMPFD1. 1 PublicationCorresponds to variant rs121909329dbSNPEnsembl.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 rs121909335dbSNPEnsembl.1
Natural variantiVAR_033021191R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 PublicationsCorresponds to variant rs121909334dbSNPEnsembl.1
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. 4 PublicationsCorresponds to variant rs121909331dbSNPEnsembl.1
Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14)1 Publication
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_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. 8 PublicationsCorresponds to variant rs121909329dbSNPEnsembl.1
Natural variantiVAR_065910159R → G in ALS14. 2 PublicationsCorresponds to variant rs387906789dbSNPEnsembl.1
Natural variantiVAR_033021191R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 PublicationsCorresponds to variant rs121909334dbSNPEnsembl.1
Natural variantiVAR_065911592D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 PublicationCorresponds to variant rs387906790dbSNPEnsembl.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 Publication1
Natural variantiVAR_076467185E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
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. 1 Publication1
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. Defect in ubiquitin-dependent protein degradation by the proteasome; when associated with Q-305. 2 Publications1

Keywords - Diseasei

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

Organism-specific databases

DisGeNETi7415.
MalaCardsiVCP.
MIMi167320. phenotype.
613954. phenotype.
616687. phenotype.
OpenTargetsiENSG00000165280.
Orphaneti329478. Adult-onset distal myopathy due to VCP mutation.
803. Amyotrophic lateral sclerosis.
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.
100069. Semantic dementia.
329475. Spastic paraplegia - Paget disease of bone.
PharmGKBiPA37289.

Chemistry databases

ChEMBLiCHEMBL1075145.

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
Modified residuei13PhosphoserineCombined sources1
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.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, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP55072.
PaxDbiP55072.
PeptideAtlasiP55072.
PRIDEiP55072.
TopDownProteomicsiP55072.

2D gel databases

DOSAC-COBS-2DPAGEP55072.
OGPiP55072.
REPRODUCTION-2DPAGEIPI00022774.
P55072.

PTM databases

iPTMnetiP55072.
PhosphoSitePlusiP55072.
SwissPalmiP55072.

Expressioni

Gene expression databases

BgeeiENSG00000165280.
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 UFD1L, binding to this heterodimer inhibits Golgi-membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1L 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 VIMP/SELS 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 UBXN6, 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. Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, STT3A, VCP AND VIMP. Interacts with KIAA0196. 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 VIMP. Forms a complex with UBQLN1 and UBXN4. Interacts (via the PIM motif) with RNF31 (via the PUB domain) (PubMed:24726327).By similarity30 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-355164,EBI-355164
AMFRQ9UKV58EBI-355164,EBI-1046367
ASPSCR1Q9BZE96EBI-355164,EBI-1993677
ATXN3P542528EBI-355164,EBI-946046
ATXN3P54252-110EBI-355164,EBI-946068
CHEK2O960172EBI-355164,EBI-1180783
FCHSD2O948682EBI-355164,EBI-1215612
GRB2P629933EBI-355164,EBI-401755
NSFL1CQ9UNZ25EBI-355164,EBI-721577
PTPN3P260452EBI-355164,EBI-1047946
UBE4BB1AQ614EBI-355164,EBI-7931266
UBXN2AP685433EBI-355164,EBI-1993668
UBXN4Q925752EBI-355164,EBI-723441
UBXN6Q9BZV17EBI-355164,EBI-1993899
UBXN7O9488810EBI-355164,EBI-1993627
YWHAZP631042EBI-355164,EBI-347088

GO - Molecular functioni

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • polyubiquitin binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • protein phosphatase binding Source: BHF-UCL
  • ubiquitin-like protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi113258. 603 interactors.
DIPiDIP-33543N.
IntActiP55072. 94 interactors.
MINTiMINT-272884.
STRINGi9606.ENSP00000351777.

Chemistry databases

BindingDBiP55072.

Structurei

Secondary structure

1806
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni15 – 17Combined sources3
Beta strandi25 – 30Combined sources6
Beta strandi38 – 41Combined sources4
Helixi43 – 49Combined sources7
Beta strandi56 – 60Combined sources5
Helixi62 – 64Combined sources3
Beta strandi66 – 73Combined sources8
Beta strandi75 – 77Combined sources3
Beta strandi81 – 84Combined sources4
Helixi86 – 91Combined sources6
Beta strandi99 – 104Combined sources6
Beta strandi112 – 118Combined sources7
Helixi120 – 123Combined sources4
Helixi130 – 133Combined sources4
Helixi135 – 139Combined sources5
Turni140 – 142Combined sources3
Beta strandi145 – 147Combined sources3
Beta strandi151 – 155Combined sources5
Beta strandi157 – 175Combined sources19
Beta strandi181 – 183Combined sources3
Helixi191 – 193Combined sources3
Beta strandi198 – 200Combined sources3
Helixi203 – 205Combined sources3
Helixi210 – 219Combined sources10
Helixi221 – 225Combined sources5
Helixi227 – 233Combined sources7
Beta strandi240 – 244Combined sources5
Beta strandi246 – 250Combined sources5
Helixi251 – 261Combined sources11
Beta strandi263 – 270Combined sources8
Helixi271 – 275Combined sources5
Helixi281 – 295Combined sources15
Beta strandi298 – 305Combined sources8
Helixi306 – 308Combined sources3
Helixi313 – 315Combined sources3
Helixi319 – 333Combined sources15
Helixi335 – 337Combined sources3
Beta strandi341 – 348Combined sources8
Helixi350 – 352Combined sources3
Helixi355 – 358Combined sources4
Beta strandi365 – 368Combined sources4
Helixi374 – 385Combined sources12
Beta strandi388 – 390Combined sources3
Helixi396 – 401Combined sources6
Helixi408 – 424Combined sources17
Turni425 – 429Combined sources5
Beta strandi432 – 436Combined sources5
Helixi439 – 444Combined sources6
Helixi449 – 457Combined sources9
Beta strandi458 – 461Combined sources4
Turni462 – 468Combined sources7
Helixi476 – 478Combined sources3
Helixi483 – 493Combined sources11
Helixi495 – 498Combined sources4
Helixi500 – 506Combined sources7
Beta strandi513 – 523Combined sources11
Helixi524 – 534Combined sources11
Beta strandi538 – 543Combined sources6
Helixi544 – 549Combined sources6
Turni552 – 554Combined sources3
Helixi555 – 568Combined sources14
Beta strandi571 – 577Combined sources7
Helixi580 – 586Combined sources7
Helixi595 – 610Combined sources16
Helixi613 – 615Combined sources3
Beta strandi617 – 624Combined sources8
Helixi626 – 628Combined sources3
Helixi631 – 634Combined sources4
Beta strandi641 – 644Combined sources4
Helixi650 – 660Combined sources11
Beta strandi662 – 664Combined sources3
Helixi672 – 678Combined sources7
Helixi684 – 705Combined sources22
Helixi733 – 742Combined sources10
Helixi749 – 761Combined sources13
Helixi762 – 766Combined sources5

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[»]
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[»]
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.
GeneTreeiENSGT00860000133780.
HOGENOMiHOG000223224.
HOVERGENiHBG001226.
InParanoidiP55072.
KOiK13525.
OMAiMADSKGD.
OrthoDBiEOG091G024K.
PhylomeDBiP55072.
TreeFamiTF300542.

Family and domain databases

Gene3Di3.10.330.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR005938. AAA_ATPase_CDC48.
IPR009010. Asp_de-COase-like_dom.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR004201. Cdc48_dom2.
IPR029067. CDC48_domain_2-like.
IPR003338. CDC4_N-term_subdom.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
[Graphical view]
PfamiPF00004. AAA. 2 hits.
PF02933. CDC48_2. 1 hit.
PF02359. CDC48_N. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
SM01072. CDC48_2. 1 hit.
SM01073. CDC48_N. 1 hit.
[Graphical view]
SUPFAMiSSF50692. SSF50692. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF54585. SSF54585. 1 hit.
TIGRFAMsiTIGR01243. CDC48. 1 hit.
PROSITEiPS00674. AAA. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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. 3 PublicationsCorresponds to variant rs121909332dbSNPEnsembl.1
Natural variantiVAR_07646497G → E in CMT2Y; increased ATPase activity. 1 Publication1
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 rs121909330dbSNPEnsembl.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. 8 PublicationsCorresponds to variant rs121909329dbSNPEnsembl.1
Natural variantiVAR_033019155R → P in IBMPFD1. 1 PublicationCorresponds to variant rs121909329dbSNPEnsembl.1
Natural variantiVAR_076466155R → S in IBMPFD1; impaired autophagic function. 1 Publication1
Natural variantiVAR_065910159R → G in ALS14. 2 PublicationsCorresponds to variant rs387906789dbSNPEnsembl.1
Natural variantiVAR_033020159R → H in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1. 1 PublicationCorresponds to variant rs121909335dbSNPEnsembl.1
Natural variantiVAR_076467185E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 Publication1
Natural variantiVAR_033021191R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 PublicationsCorresponds to variant rs121909334dbSNPEnsembl.1
Natural variantiVAR_076468198L → W Polymorphism; increased ATPase activity. 1 Publication1
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. 4 PublicationsCorresponds to variant rs121909331dbSNPEnsembl.1
Natural variantiVAR_065911592D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 PublicationCorresponds to variant rs387906790dbSNPEnsembl.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. Translation: CAH70993.1.
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.

Keywords - Coding sequence diversityi

Polymorphism

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. Translation: CAH70993.1.
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[»]
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[»]
ProteinModelPortaliP55072.
SMRiP55072.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113258. 603 interactors.
DIPiDIP-33543N.
IntActiP55072. 94 interactors.
MINTiMINT-272884.
STRINGi9606.ENSP00000351777.

Chemistry databases

BindingDBiP55072.
ChEMBLiCHEMBL1075145.

Protein family/group databases

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

PTM databases

iPTMnetiP55072.
PhosphoSitePlusiP55072.
SwissPalmiP55072.

Polymorphism and mutation databases

BioMutaiVCP.
DMDMi6094447.

2D gel databases

DOSAC-COBS-2DPAGEP55072.
OGPiP55072.
REPRODUCTION-2DPAGEIPI00022774.
P55072.

Proteomic databases

EPDiP55072.
PaxDbiP55072.
PeptideAtlasiP55072.
PRIDEiP55072.
TopDownProteomicsiP55072.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358901; ENSP00000351777; ENSG00000165280.
GeneIDi7415.
KEGGihsa:7415.

Organism-specific databases

CTDi7415.
DisGeNETi7415.
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.
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.
100069. Semantic dementia.
329475. Spastic paraplegia - Paget disease of bone.
PharmGKBiPA37289.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0730. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00860000133780.
HOGENOMiHOG000223224.
HOVERGENiHBG001226.
InParanoidiP55072.
KOiK13525.
OMAiMADSKGD.
OrthoDBiEOG091G024K.
PhylomeDBiP55072.
TreeFamiTF300542.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165280-MONOMER.
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.
SignaLinkiP55072.
SIGNORiP55072.

Miscellaneous databases

ChiTaRSiVCP. human.
EvolutionaryTraceiP55072.
GeneWikiiValosin-containing_protein.
GenomeRNAii7415.
PROiP55072.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165280.
CleanExiHS_VCP.
ExpressionAtlasiP55072. baseline and differential.
GenevisibleiP55072. HS.

Family and domain databases

Gene3Di3.10.330.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR005938. AAA_ATPase_CDC48.
IPR009010. Asp_de-COase-like_dom.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR004201. Cdc48_dom2.
IPR029067. CDC48_domain_2-like.
IPR003338. CDC4_N-term_subdom.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
[Graphical view]
PfamiPF00004. AAA. 2 hits.
PF02933. CDC48_2. 1 hit.
PF02359. CDC48_N. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
SM01072. CDC48_2. 1 hit.
SM01073. CDC48_N. 1 hit.
[Graphical view]
SUPFAMiSSF50692. SSF50692. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF54585. SSF54585. 1 hit.
TIGRFAMsiTIGR01243. CDC48. 1 hit.
PROSITEiPS00674. AAA. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTERA_HUMAN
AccessioniPrimary (citable) accession number: P55072
Secondary accession number(s): B2R5T8
, Q0V924, Q2TAI5, Q969G7, Q9UCD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 185 of the entry and version 4 of the sequence. [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

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

Keywords - Technical termi

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

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.