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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei348 – 3481ATP1 Publication
Binding sitei384 – 3841ATP1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi247 – 2537ATP1 Publication
Nucleotide bindingi521 – 5266ATPBy similarity

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
  • 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
  • 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: ParkinsonsUK-UCL
  • 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

ReactomeiR-HSA-110320. Translesion Synthesis by POLH.
R-HSA-3371511. HSF1 activation.
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti95 – 951R → 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 Publications
Corresponds to variant rs121909332 [ dbSNP | Ensembl ].
VAR_033016
Natural varianti126 – 1261I → F in IBMPFD1; unknown pathological significance. 1 Publication
VAR_076465
Natural varianti155 – 1551R → C in IBMPFD1; also in one patient without evidence of Paget disease of the bone. 2 Publications
Corresponds to variant rs121909330 [ dbSNP | Ensembl ].
VAR_033017
Natural varianti155 – 1551R → 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 Publications
Corresponds to variant rs121909329 [ dbSNP | Ensembl ].
VAR_033018
Natural varianti155 – 1551R → P in IBMPFD1. 1 Publication
Corresponds to variant rs121909329 [ dbSNP | Ensembl ].
VAR_033019
Natural varianti155 – 1551R → S in IBMPFD1; impaired autophagic function. 1 Publication
VAR_076466
Natural varianti159 – 1591R → H in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1. 1 Publication
Corresponds to variant rs121909335 [ dbSNP | Ensembl ].
VAR_033020
Natural varianti191 – 1911R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 Publications
Corresponds to variant rs121909334 [ dbSNP | Ensembl ].
VAR_033021
Natural varianti232 – 2321A → 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 Publications
Corresponds to variant rs121909331 [ dbSNP | Ensembl ].
VAR_033022
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti155 – 1551R → 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 Publications
Corresponds to variant rs121909329 [ dbSNP | Ensembl ].
VAR_033018
Natural varianti159 – 1591R → G in ALS14. 2 Publications
Corresponds to variant rs387906789 [ dbSNP | Ensembl ].
VAR_065910
Natural varianti191 – 1911R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 Publications
Corresponds to variant rs121909334 [ dbSNP | Ensembl ].
VAR_033021
Natural varianti592 – 5921D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 Publication
Corresponds to variant rs387906790 [ dbSNP | Ensembl ].
VAR_065911
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti97 – 971G → E in CMT2Y; increased ATPase activity. 1 Publication
VAR_076464
Natural varianti185 – 1851E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 Publication
VAR_076467

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi53 – 531R → A: Minor effect on affinity for ATP and ADP. 1 Publication
Mutagenesisi86 – 861R → A: Strongly increased affinity for ATP. Strongly reduced affinity for ADP. 1 Publication
Mutagenesisi251 – 2511K → Q: Impairs ERAD degradation of HMGCR and does not inhibit interaction with RHBDD1; when associated with Q-524. 2 Publications
Mutagenesisi305 – 3051E → Q: Defect in ubiquitin-dependent protein degradation by the proteasome; when associated with Q-578. 1 Publication
Mutagenesisi312 – 3121K → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi313 – 3131R → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi314 – 3141E → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi314 – 3141Missing : Strongly impairs methylation by VCPKMT. 1 Publication
Mutagenesisi315 – 3151K → L, Q or R: Abolishes methylation by VCPKMT. 2 Publications
Mutagenesisi316 – 3161T → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi317 – 3171H → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi318 – 3181G → A: Does not affect methylation by VCPKMT. 1 Publication
Mutagenesisi524 – 5241K → A: Impairs catalytic activity of RNF19A toward SOD1 mutant. Does not inhibit interaction with RHBDD1; when associated with A-251. 3 Publications
Mutagenesisi524 – 5241K → Q: Impairs ERAD degradation of HMGCR; when associated with Q-251. 3 Publications
Mutagenesisi578 – 5781E → Q: Does not inhibit interaction with RHBDD1. Defect in ubiquitin-dependent protein degradation by the proteasome; when associated with Q-305. 2 Publications

Keywords - Diseasei

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

Organism-specific databases

MalaCardsiVCP.
MIMi167320. phenotype.
613954. phenotype.
616687. phenotype.
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

ChEMBLiCHEMBL1075145.

Polymorphism and mutation databases

BioMutaiVCP.
DMDMi6094447.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources2 Publications
Chaini2 – 806805Transitional endoplasmic reticulum ATPasePRO_0000084572Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources1 Publication
Modified residuei3 – 31PhosphoserineCombined sources
Modified residuei7 – 71PhosphoserineCombined sources
Modified residuei13 – 131PhosphoserineCombined sources
Modified residuei37 – 371PhosphoserineCombined sources
Modified residuei315 – 3151N6,N6,N6-trimethyllysine; by VCPKMT2 Publications
Modified residuei436 – 4361PhosphothreonineCombined sources
Modified residuei462 – 4621PhosphoserineCombined sources
Modified residuei502 – 5021N6-acetyllysineBy similarity
Modified residuei505 – 5051N6-acetyllysineBy similarity
Modified residuei668 – 6681N6-acetyllysine; alternateBy similarity
Modified residuei668 – 6681N6-succinyllysine; alternateBy similarity
Modified residuei702 – 7021PhosphoserineCombined sources
Modified residuei754 – 7541N6-acetyllysineBy similarity
Modified residuei770 – 7701PhosphoserineCombined sources
Modified residuei775 – 7751PhosphoserineCombined sources
Modified residuei787 – 7871PhosphoserineCombined sources
Modified residuei805 – 8051PhosphotyrosineBy similarity

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.
PhosphoSiteiP55072.
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.By similarity29 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-355164,EBI-355164
AMFRQ9UKV58EBI-355164,EBI-1046367
ASPSCR1Q9BZE94EBI-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
UBXN4Q925752EBI-355164,EBI-723441
UBXN6Q9BZV17EBI-355164,EBI-1993899
YWHAZP631042EBI-355164,EBI-347088

GO - Molecular functioni

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • 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. 601 interactions.
DIPiDIP-33543N.
IntActiP55072. 76 interactions.
MINTiMINT-272884.
STRINGi9606.ENSP00000351777.

Chemistry

BindingDBiP55072.

Structurei

Secondary structure

1
806
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni15 – 173Combined sources
Beta strandi25 – 306Combined sources
Beta strandi38 – 414Combined sources
Helixi43 – 497Combined sources
Beta strandi56 – 605Combined sources
Helixi62 – 643Combined sources
Beta strandi66 – 738Combined sources
Beta strandi75 – 773Combined sources
Beta strandi81 – 844Combined sources
Helixi86 – 916Combined sources
Beta strandi99 – 1046Combined sources
Beta strandi112 – 1187Combined sources
Helixi120 – 1234Combined sources
Helixi130 – 1334Combined sources
Helixi135 – 1395Combined sources
Turni140 – 1423Combined sources
Beta strandi145 – 1473Combined sources
Beta strandi151 – 1555Combined sources
Beta strandi157 – 17519Combined sources
Beta strandi181 – 1833Combined sources
Helixi191 – 1933Combined sources
Beta strandi198 – 2003Combined sources
Helixi203 – 2053Combined sources
Helixi210 – 21910Combined sources
Helixi221 – 2255Combined sources
Helixi227 – 2337Combined sources
Beta strandi240 – 2445Combined sources
Beta strandi246 – 2505Combined sources
Helixi251 – 26111Combined sources
Beta strandi263 – 2708Combined sources
Helixi271 – 2755Combined sources
Helixi281 – 29515Combined sources
Beta strandi298 – 3058Combined sources
Helixi306 – 3083Combined sources
Helixi313 – 3153Combined sources
Helixi319 – 33315Combined sources
Helixi335 – 3373Combined sources
Beta strandi341 – 3488Combined sources
Helixi350 – 3523Combined sources
Helixi355 – 3584Combined sources
Beta strandi365 – 3684Combined sources
Helixi374 – 38512Combined sources
Beta strandi388 – 3903Combined sources
Helixi396 – 4016Combined sources
Helixi408 – 42417Combined sources
Turni425 – 4295Combined sources
Beta strandi432 – 4365Combined sources
Helixi439 – 4446Combined sources
Helixi449 – 4579Combined sources
Beta strandi458 – 4614Combined sources
Turni462 – 4687Combined sources
Helixi476 – 4783Combined sources
Helixi483 – 49311Combined sources
Helixi495 – 4984Combined sources
Helixi500 – 5067Combined sources
Beta strandi513 – 52311Combined sources
Helixi524 – 53411Combined sources
Beta strandi538 – 5436Combined sources
Helixi544 – 5496Combined sources
Turni552 – 5543Combined sources
Helixi555 – 56814Combined sources
Beta strandi571 – 5777Combined sources
Helixi580 – 5867Combined sources
Helixi595 – 61016Combined sources
Helixi613 – 6153Combined sources
Beta strandi617 – 6248Combined sources
Helixi626 – 6283Combined sources
Helixi631 – 6344Combined sources
Beta strandi641 – 6444Combined sources
Helixi650 – 66011Combined sources
Beta strandi662 – 6643Combined sources
Helixi672 – 6787Combined sources
Helixi684 – 70522Combined sources
Helixi733 – 74210Combined sources
Helixi749 – 76113Combined sources
Helixi762 – 7665Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
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. Positions 14-763.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55072.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni797 – 80610Interaction with UBXN6

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Phylogenomic databases

eggNOGiKOG0730. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00810000125456.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti169 – 1691D → H in AAI21795 (PubMed:15489334).Curated
Sequence conflicti312 – 3121K → I in BAG35235 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti95 – 951R → 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 Publications
Corresponds to variant rs121909332 [ dbSNP | Ensembl ].
VAR_033016
Natural varianti97 – 971G → E in CMT2Y; increased ATPase activity. 1 Publication
VAR_076464
Natural varianti126 – 1261I → F in IBMPFD1; unknown pathological significance. 1 Publication
VAR_076465
Natural varianti155 – 1551R → C in IBMPFD1; also in one patient without evidence of Paget disease of the bone. 2 Publications
Corresponds to variant rs121909330 [ dbSNP | Ensembl ].
VAR_033017
Natural varianti155 – 1551R → 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 Publications
Corresponds to variant rs121909329 [ dbSNP | Ensembl ].
VAR_033018
Natural varianti155 – 1551R → P in IBMPFD1. 1 Publication
Corresponds to variant rs121909329 [ dbSNP | Ensembl ].
VAR_033019
Natural varianti155 – 1551R → S in IBMPFD1; impaired autophagic function. 1 Publication
VAR_076466
Natural varianti159 – 1591R → G in ALS14. 2 Publications
Corresponds to variant rs387906789 [ dbSNP | Ensembl ].
VAR_065910
Natural varianti159 – 1591R → H in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1. 1 Publication
Corresponds to variant rs121909335 [ dbSNP | Ensembl ].
VAR_033020
Natural varianti185 – 1851E → K in CMT2Y; normal ATPase activity; impaired autophagic function. 1 Publication
VAR_076467
Natural varianti191 – 1911R → Q in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1. 3 Publications
Corresponds to variant rs121909334 [ dbSNP | Ensembl ].
VAR_033021
Natural varianti198 – 1981L → W Polymorphism; increased ATPase activity. 1 Publication
VAR_076468
Natural varianti232 – 2321A → 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 Publications
Corresponds to variant rs121909331 [ dbSNP | Ensembl ].
VAR_033022
Natural varianti592 – 5921D → N in ALS14; ALS14 patients do not show frontotemporal dementia. 1 Publication
Corresponds to variant rs387906790 [ dbSNP | Ensembl ].
VAR_065911

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
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[»]
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. Positions 14-763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113258. 601 interactions.
DIPiDIP-33543N.
IntActiP55072. 76 interactions.
MINTiMINT-272884.
STRINGi9606.ENSP00000351777.

Chemistry

BindingDBiP55072.
ChEMBLiCHEMBL1075145.

Protein family/group databases

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

PTM databases

iPTMnetiP55072.
PhosphoSiteiP55072.
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.
GeneCardsiVCP.
GeneReviewsiVCP.
HGNCiHGNC:12666. VCP.
HPAiCAB005593.
HPA012728.
HPA012814.
MalaCardsiVCP.
MIMi167320. phenotype.
601023. gene.
613954. phenotype.
616687. phenotype.
neXtProtiNX_P55072.
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.
GeneTreeiENSGT00810000125456.
HOGENOMiHOG000223224.
HOVERGENiHBG001226.
InParanoidiP55072.
KOiK13525.
OMAiMADSKGD.
OrthoDBiEOG091G024K.
PhylomeDBiP55072.
TreeFamiTF300542.

Enzyme and pathway databases

ReactomeiR-HSA-110320. Translesion Synthesis by POLH.
R-HSA-3371511. HSF1 activation.
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
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: September 7, 2016
This is version 182 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.