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P46462

- TERA_RAT

UniProt

P46462 - TERA_RAT

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Protein

Transitional endoplasmic reticulum ATPase

Gene

Vcp

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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. 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. 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.By similarity2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei348 – 3481ATPBy similarity
Binding sitei384 – 3841ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi247 – 2537ATPBy similarity

GO - Molecular functioni

  1. ADP binding Source: RGD
  2. ATPase activity Source: RGD
  3. ATP binding Source: BHF-UCL
  4. deubiquitinase activator activity Source: Ensembl
  5. identical protein binding Source: BHF-UCL
  6. lipid binding Source: UniProtKB-KW
  7. poly(A) RNA binding Source: Ensembl
  8. protein complex binding Source: RGD
  9. receptor binding Source: RGD

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  2. aggresome assembly Source: Ensembl
  3. ATP catabolic process Source: GOC
  4. cellular response to DNA damage stimulus Source: UniProtKB
  5. double-strand break repair Source: UniProtKB
  6. ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  7. ER to Golgi vesicle-mediated transport Source: RGD
  8. positive regulation of Lys63-specific deubiquitinase activity Source: Ensembl
  9. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: RGD
  10. positive regulation of protein complex assembly Source: Ensembl
  11. positive regulation of protein K63-linked deubiquitination Source: Ensembl
  12. protein hexamerization Source: RGD
  13. protein homooligomerization Source: RGD
  14. protein N-linked glycosylation via asparagine Source: UniProtKB
  15. protein ubiquitination Source: UniProtKB
  16. retrograde protein transport, ER to cytosol Source: Ensembl
  17. translesion synthesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

DNA damage, DNA repair, Transport

Keywords - Ligandi

ATP-binding, Lipid-binding, Nucleotide-binding

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 5

Organism-specific databases

RGDi621595. Vcp.

Subcellular locationi

Cytoplasmcytosol 1 Publication. Nucleus 1 Publication. Endoplasmic reticulum By similarity
Note: 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 (By similarity).By similarity

GO - Cellular componenti

  1. cytosol Source: MGI
  2. endoplasmic reticulum Source: RGD
  3. extracellular vesicular exosome Source: Ensembl
  4. Hrd1p ubiquitin ligase complex Source: Ensembl
  5. intracellular membrane-bounded organelle Source: RGD
  6. lipid particle Source: Ensembl
  7. nucleus Source: UniProtKB-KW
  8. perinuclear region of cytoplasm Source: Ensembl
  9. proteasome complex Source: Ensembl
  10. site of double-strand break Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 806805Transitional endoplasmic reticulum ATPasePRO_0000084575Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei3 – 31PhosphoserineBy similarity
Modified residuei37 – 371PhosphoserineBy similarity
Modified residuei315 – 3151N6,N6,N6-trimethyllysine; by VCPKMTBy similarity
Modified residuei436 – 4361PhosphothreonineBy similarity
Modified residuei502 – 5021N6-acetyllysineBy similarity
Modified residuei505 – 5051N6-acetyllysineBy similarity
Modified residuei668 – 6681N6-acetyllysine; alternateBy similarity
Modified residuei668 – 6681N6-succinyllysine; alternateBy similarity
Modified residuei754 – 7541N6-acetyllysineBy similarity
Modified residuei770 – 7701PhosphoserineBy similarity
Modified residuei775 – 7751PhosphoserineBy similarity
Modified residuei787 – 7871PhosphoserineBy similarity
Modified residuei805 – 8051PhosphotyrosineBy similarity

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).By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP46462.
PRIDEiP46462.

2D gel databases

World-2DPAGE0004:P46462.

PTM databases

PhosphoSiteiP46462.

Expressioni

Gene expression databases

GenevestigatoriP46462.

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 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 UBXD2 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 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 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. Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, STT3A, VCP AND VIMP. Interacts with KIAA0196. Interacts with UBOX5.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nsfl1cO3598710EBI-399011,EBI-1993760

Protein-protein interaction databases

BioGridi250528. 20 interactions.
IntActiP46462. 7 interactions.
MINTiMINT-1954391.
STRINGi10116.ENSRNOP00000040121.

Structurei

3D structure databases

ProteinModelPortaliP46462.
SMRiP46462. Positions 18-763.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni797 – 80610Interaction with UBXN6By similarity

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Phylogenomic databases

eggNOGiCOG0464.
GeneTreeiENSGT00740000115575.
HOGENOMiHOG000223224.
HOVERGENiHBG001226.
InParanoidiP46462.
KOiK13525.
OMAiHKKVNLT.
OrthoDBiEOG7H4DSW.
PhylomeDBiP46462.
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.

P46462 [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:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U11760 mRNA. Translation: AAC52154.1 .
BC060518 mRNA. Translation: AAH60518.1 .
PIRi A55190.
RefSeqi NP_446316.1. NM_053864.2.
UniGenei Rn.98891.

3D structure databases

ProteinModelPortali P46462.
SMRi P46462. Positions 18-763.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 250528. 20 interactions.
IntActi P46462. 7 interactions.
MINTi MINT-1954391.
STRINGi 10116.ENSRNOP00000040121.

PTM databases

PhosphoSitei P46462.

2D gel databases

World-2DPAGE 0004:P46462.

Proteomic databases

PaxDbi P46462.
PRIDEi P46462.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000046102 ; ENSRNOP00000040121 ; ENSRNOG00000034242 .
GeneIDi 116643.
KEGGi rno:116643.
UCSCi RGD:621595. rat.

Organism-specific databases

CTDi 7415.
RGDi 621595. Vcp.

Phylogenomic databases

eggNOGi COG0464.
GeneTreei ENSGT00740000115575.
HOGENOMi HOG000223224.
HOVERGENi HBG001226.
InParanoidi P46462.
KOi K13525.
OMAi HKKVNLT.
OrthoDBi EOG7H4DSW.
PhylomeDBi P46462.
TreeFami TF300542.

Miscellaneous databases

NextBioi 619375.
PROi P46462.

Gene expression databases

Genevestigatori P46462.

Family and domain databases

Gene3Di 3.10.330.10. 1 hit.
3.40.50.300. 2 hits.
InterProi IPR003593. 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 ]
Pfami PF00004. AAA. 2 hits.
PF02933. CDC48_2. 1 hit.
PF02359. CDC48_N. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view ]
SMARTi SM00382. AAA. 2 hits.
SM01072. CDC48_2. 1 hit.
SM01073. CDC48_N. 1 hit.
[Graphical view ]
SUPFAMi SSF50692. SSF50692. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF54585. SSF54585. 1 hit.
TIGRFAMsi TIGR01243. CDC48. 1 hit.
PROSITEi PS00674. AAA. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of the principal ATPase associated with transitional endoplasmic reticulum of rat liver."
    Zhang L., Ashendel C.L., Becker G.W., Morre D.J.
    J. Cell Biol. 127:1871-1883(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  3. Lubec G., Diao W.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 46-53; 149-155; 192-210; 218-225; 240-251; 296-312; 366-386; 454-465; 616-638; 669-677 AND 701-709, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Hippocampus.
  4. "Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro."
    Rabouille C., Kondo H., Newman R., Hui N., Freemont P., Warren G.
    Cell 92:603-610(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH STX5A.
  5. "A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways."
    Meyer H.H., Shorter J.G., Seemann J., Pappin D., Warren G.
    EMBO J. 19:2181-2192(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NPLOC4; UFD1L; NSFL1C AND UBE4B, SUBCELLULAR LOCATION.
  6. Cited for: FUNCTION.
  7. "Phospholipid species act as modulators in p97/p47-mediated fusion of Golgi membranes."
    Pecheur E.-I., Martin I., Maier O., Bakowsky U., Ruysschaert J.-M., Hoekstra D.
    Biochemistry 41:9813-9823(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MEMBRANES.
  8. "Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4."
    Meyer H.H., Wang Y., Warren G.
    EMBO J. 21:5645-5652(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NSFL1C; NAP1L4 AND UFD1L.
  9. "VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo."
    Uchiyama K., Jokitalo E., Kano F., Murata M., Zhang X., Canas B., Newman R., Rabouille C., Pappin D., Freemont P., Kondo H.
    J. Cell Biol. 159:855-866(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VCIP135.
  10. "The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle."
    Uchiyama K., Jokitalo E., Lindman M., Jackman M., Kano F., Murata M., Zhang X., Kondo H.
    J. Cell Biol. 161:1067-1079(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.

Entry informationi

Entry nameiTERA_RAT
AccessioniPrimary (citable) accession number: P46462
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 141 of the entry and version 3 of the sequence. [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

External Data

Dasty 3