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Protein

Transitional endoplasmic reticulum ATPase

Gene

Vcp

Organism
Rattus norvegicus (Rat)
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) (PubMed:10930451, PubMed:12411482). Vesicle budding from the tER is an ATP-dependent process (PubMed:10930451, PubMed:12411482). 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 (PubMed:10930451, PubMed:12411482). 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. 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. 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 (By similarity). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (By similarity). May more particularly play a role in caveolins sorting in cells (By similarity).By similarity2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei348ATPBy similarity1
Binding sitei384ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi247 – 253ATPBy similarity7
Nucleotide bindingi521 – 526ATPBy similarity6

GO - Molecular functioni

  • ADP binding Source: RGD
  • ATPase activity Source: RGD
  • ATP binding Source: BHF-UCL
  • BAT3 complex binding Source: RGD
  • deubiquitinase activator activity Source: RGD
  • identical protein binding Source: BHF-UCL
  • K48-linked polyubiquitin modification-dependent protein binding Source: RGD
  • lipid binding Source: UniProtKB-KW
  • MHC class I protein binding Source: RGD
  • polyubiquitin modification-dependent protein binding Source: RGD
  • protein complex binding Source: RGD
  • protein domain specific binding Source: RGD
  • protein phosphatase binding Source: RGD
  • receptor binding Source: RGD
  • RNA binding Source: RGD
  • ubiquitin-like protein ligase binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD
  • ubiquitin-specific protease binding Source: RGD

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.6.4.6. 5301.
ReactomeiR-RNO-110320. Translesion Synthesis by POLH.
R-RNO-3371511. HSF1 activation.
R-RNO-382556. ABC-family proteins mediated transport.
R-RNO-532668. N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
R-RNO-5358346. Hedgehog ligand biogenesis.
R-RNO-5689896. Ovarian tumor domain proteases.
R-RNO-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Transitional endoplasmic reticulum ATPase (EC:3.6.4.6By similarity)
Short name:
TER ATPase
Alternative name(s):
15S Mg(2+)-ATPase p97 subunit
Valosin-containing protein
Short name:
VCP
Gene namesi
Name:Vcp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi621595. Vcp.

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000845752 – 806Transitional endoplasmic reticulum ATPaseAdd BLAST805

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei3PhosphoserineCombined sources1
Modified residuei7PhosphoserineCombined sources1
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei13PhosphoserineBy similarity1
Cross-linki18Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei37PhosphoserineBy similarity1
Modified residuei315N6,N6,N6-trimethyllysine; by VCPKMTBy similarity1
Modified residuei436PhosphothreonineBy similarity1
Modified residuei462PhosphoserineBy similarity1
Modified residuei502N6-acetyllysineBy similarity1
Modified residuei505N6-acetyllysineBy similarity1
Modified residuei668N6-acetyllysine; alternateBy similarity1
Modified residuei668N6-succinyllysine; alternateBy similarity1
Modified residuei702PhosphoserineBy similarity1
Modified residuei754N6-acetyllysineBy similarity1
Modified residuei770PhosphoserineBy similarity1
Modified residuei775PhosphoserineBy similarity1
Modified residuei787PhosphoserineBy similarity1
Modified residuei805PhosphotyrosineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP46462.
PRIDEiP46462.

2D gel databases

World-2DPAGEi0004:P46462.

PTM databases

iPTMnetiP46462.
PhosphoSitePlusiP46462.

Expressioni

Gene expression databases

BgeeiENSRNOG00000034242.
GenevisibleiP46462. RN.

Interactioni

Subunit structurei

Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with RHBDD1 (via C-terminal domain). 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 SPRTN; leading to recruitment to stalled replication forks. 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. 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 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 (By similarity). Interacts (via the PIM motif) with RNF31 (via the PUB domain) (By similarity). 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 (By similarity). Interacts with BAG6 (By similarity). Interacts with UBXN10 (By similarity). Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (By similarity). Forms a ternary complex with CAV1 and UBXN6. Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (By similarity). Interacts with ANKZF1 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nsfl1cO3598712EBI-399011,EBI-1993760

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250528. 24 interactors.
CORUMiP46462.
IntActiP46462. 9 interactors.
MINTiMINT-1954391.
STRINGi10116.ENSRNOP00000040121.

Structurei

3D structure databases

ProteinModelPortaliP46462.
SMRiP46462.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni797 – 806Interaction with UBXN6By similarity10

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi802 – 806PIM motifBy similarity5

Domaini

The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31.By similarity

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Phylogenomic databases

eggNOGiKOG0730. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00900000141071.
HOGENOMiHOG000223224.
HOVERGENiHBG001226.
InParanoidiP46462.
KOiK13525.
OMAiPIDDTTE.
OrthoDBiEOG091G024K.
PhylomeDBiP46462.
TreeFamiTF300542.

Family and domain databases

Gene3Di3.10.330.10. 1 hit.
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.

Sequencei

Sequence statusi: Complete.

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

P46462-1 [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 TGGNVYTEDN

DDDLYG
Length:806
Mass (Da):89,349
Last modified:January 23, 2007 - v3
Checksum:i501B721D205EBA8A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11760 mRNA. Translation: AAC52154.1.
BC060518 mRNA. Translation: AAH60518.1.
PIRiA55190.
RefSeqiNP_446316.1. NM_053864.2.
UniGeneiRn.98891.

Genome annotation databases

EnsembliENSRNOT00000046102; ENSRNOP00000040121; ENSRNOG00000034242.
GeneIDi116643.
KEGGirno:116643.
UCSCiRGD:621595. rat.

Similar proteinsi

Entry informationi

Entry nameiTERA_RAT
AccessioniPrimary (citable) accession number: P46462
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: November 22, 2017
This is version 170 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families