UniProt Accession

 TERA_HUMAN; P55072; B2R5T8; Q0V924; Q2TAI5; Q969G7; Q9UCD5 

Genbank Protein ID

 AC004472; AF100752; AK312310; AL353795; CH471071; BC110913; BC121794; Z70768 

Genbank Nucleotide ID

 AAC07984.1; AAD43016.1; BAG35235.1; CAH70993.1; EAW58404.1; AAI10914.1; AAI21795.1; CAA94809.1 

Protein Name

 Transitional endoplasmic reticulum ATPase 

Protein Synonyms/Alias

 TER ATPase; 15S Mg(2+)-ATPase p97 subunit; Valosin-containing protein; VCP 

Gene Name

 VCP 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
8	MASGADSKGDDLSTA	acetylation	[1]
8	MASGADSKGDDLSTA	ubiquitination	[2, 3, 4, 5, 6, 7, 8]
18	DLSTAILKQKNRPNR	acetylation	[1]
18	DLSTAILKQKNRPNR	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
20	STAILKQKNRPNRLI	ubiquitination	[4, 6, 8, 11]
45	VVSLSQPKMDELQLF	ubiquitination	[6, 9, 10, 11]
60	RGDTVLLKGKKRREA	acetylation	[1]
60	RGDTVLLKGKKRREA	ubiquitination	[4, 6, 11]
62	DTVLLKGKKRREAVC	acetylation	[1]
63	TVLLKGKKRREAVCI	ubiquitination	[6]
81	DDTCSDEKIRMNRVV	acetylation	[1]
81	DDTCSDEKIRMNRVV	ubiquitination	[6]
109	IQPCPDVKYGKRIHV	ubiquitination	[3, 4, 5, 6, 7, 9, 11, 12]
112	CPDVKYGKRIHVLPI	ubiquitination	[4, 6]
148	EAYRPIRKGDIFLVR	ubiquitination	[4, 5, 6]
164	GMRAVEFKVVETDPS	acetylation	[1]
164	GMRAVEFKVVETDPS	ubiquitination	[6]
211	DDIGGCRKQLAQIKE	ubiquitination	[3, 6, 7, 8, 9, 10]
217	RKQLAQIKEMVELPL	ubiquitination	[3, 5, 6, 7, 8, 9, 10, 11, 12]
231	LRHPALFKAIGVKPP	ubiquitination	[3, 4, 5, 6, 7, 8, 9, 10, 11]
236	LFKAIGVKPPRGILL	ubiquitination	[4, 5, 6, 8, 9, 10, 11]
251	YGPPGTGKTLIARAV	acetylation	[1]
251	YGPPGTGKTLIARAV	ubiquitination	[3, 4, 5, 6, 7, 8, 10, 11, 12]
288	ESESNLRKAFEEAEK	ubiquitination	[4, 6, 8, 9, 11]
295	KAFEEAEKNAPAIIF	ubiquitination	[6, 8, 9, 11]
312	ELDAIAPKREKTHGE	ubiquitination	[3, 4, 6, 7, 8, 9, 10, 11, 12]
315	AIAPKREKTHGEVER	acetylation	[1]
315	AIAPKREKTHGEVER	methylation	[13]
336	LTLMDGLKQRAHVIV	acetylation	[1]
336	LTLMDGLKQRAHVIV	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15]
386	EILQIHTKNMKLADD	acetylation	[1]
386	EILQIHTKNMKLADD	ubiquitination	[3, 4, 6, 7, 8, 9, 11]
389	QIHTKNMKLADDVDL	ubiquitination	[6, 8]
486	IGGLEDVKRELQELV	ubiquitination	[4, 6, 8, 9, 10, 11, 12, 14, 15]
502	YPVEHPDKFLKFGMT	ubiquitination	[3, 4, 6, 7, 8, 9, 10, 11, 12, 15]
505	EHPDKFLKFGMTPSK	acetylation	[1, 16]
505	EHPDKFLKFGMTPSK	ubiquitination	[3, 4, 5, 6, 7, 8, 9, 10, 11]
512	KFGMTPSKGVLFYGP	acetylation	[1]
512	KFGMTPSKGVLFYGP	ubiquitination	[4, 5, 6, 8, 9, 10, 14]
524	YGPPGCGKTLLAKAI	acetylation	[1]
524	YGPPGCGKTLLAKAI	ubiquitination	[3, 4, 5, 6, 7, 8, 10, 12]
529	CGKTLLAKAIANECQ	acetylation	[1]
529	CGKTLLAKAIANECQ	ubiquitination	[3, 4, 5, 6, 7, 8, 10, 11, 14, 15]
565	NVREIFDKARQAAPC	ubiquitination	[3, 6, 7]
584	DELDSIAKARGGNIG	ubiquitination	[4, 6, 8, 9, 14]
614	EMDGMSTKKNVFIIG	acetylation	[1]
614	EMDGMSTKKNVFIIG	ubiquitination	[4, 6, 8, 9, 10, 11, 14]
615	MDGMSTKKNVFIIGA	acetylation	[1]
615	MDGMSTKKNVFIIGA	ubiquitination	[6, 8, 10]
651	YIPLPDEKSRVAILK	acetylation	[16]
651	YIPLPDEKSRVAILK	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15]
658	KSRVAILKANLRKSP	acetylation	[1]
658	KSRVAILKANLRKSP	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14]
663	ILKANLRKSPVAKDV	acetylation	[1]
663	ILKANLRKSPVAKDV	ubiquitination	[4, 9, 11]
668	LRKSPVAKDVDLEFL	acetylation	[1, 16]
668	LRKSPVAKDVDLEFL	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15]
677	VDLEFLAKMTNGFSG	acetylation	[1]
696	EICQRACKLAIRESI	acetylation	[1]
696	EICQRACKLAIRESI	ubiquitination	[3, 6, 7, 8, 10]
754	VSDNDIRKYEMFAQT	acetylation	[1]
754	VSDNDIRKYEMFAQT	ubiquitination	[3, 4, 5, 6, 7, 8, 9, 10, 11, 15]

Reference

 [1] p97/valosin-containing protein (VCP) is highly modulated by phosphorylation and acetylation.
 Mori-Konya C, Kato N, Maeda R, Yasuda K, Higashimae N, Noguchi M, Koike M, Kimura Y, Ohizumi H, Hori S, Kakizuka A.
 Genes Cells. 2009 Apr;14(4):483-97. [PMID: 19335618]
 [2] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [12] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [13] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837]
 [14] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [15] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [16] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional Description

 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 (By similarity). 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. 

Sequence Annotation

 NP_BIND 247 253 ATP.
 REGION 797 806 Interaction with UBXN6.
 BINDING 348 348 ATP.
 BINDING 384 384 ATP.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 3 3 Phosphoserine.
 MOD_RES 7 7 Phosphoserine (By similarity).
 MOD_RES 37 37 Phosphoserine.
 MOD_RES 315 315 N6,N6,N6-trimethyllysine; by METTL21D.
 MOD_RES 436 436 Phosphothreonine.
 MOD_RES 770 770 Phosphoserine.
 MOD_RES 775 775 Phosphoserine.
 MOD_RES 787 787 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Amyotrophic lateral sclerosis; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; Endoplasmic reticulum; Hydrolase; Lipid-binding; Methylation; Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Transport; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 806 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0000502; C:proteasome complex; IDA:BHF-UCL.
 GO:0035861; C:site of double-strand break; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0016887; F:ATPase activity; TAS:UniProtKB.
 GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
 GO:0031593; F:polyubiquitin binding; IDA:BHF-UCL.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
 GO:0070842; P:aggresome assembly; IEA:Compara.
 GO:0006302; P:double-strand break repair; IDA:UniProtKB.
 GO:0030968; P:endoplasmic reticulum unfolded protein response; TAS:UniProtKB.
 GO:0006888; P:ER to Golgi vesicle-mediated transport; IEA:Compara.
 GO:0030433; P:ER-associated protein catabolic process; IMP:UniProtKB.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0031334; P:positive regulation of protein complex assembly; IDA:BHF-UCL.
 GO:0051260; P:protein homooligomerization; IEA:Compara.
 GO:0018279; P:protein N-linked glycosylation via asparagine; IMP:UniProtKB.
 GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
 GO:0030970; P:retrograde protein transport, ER to cytosol; IDA:UniProtKB.
 GO:0019985; P:translesion synthesis; IMP:UniProtKB. 

Interpro

 IPR003593; AAA+_ATPase.
 IPR009010; Asp_de-COase-like_dom.
 IPR005938; ATPase_AAA_CDC48.
 IPR003959; ATPase_AAA_core.
 IPR003960; ATPase_AAA_CS.
 IPR004201; Cdc48_dom2.
 IPR003338; CDC4_N-term_subdom.
 IPR027417; P-loop_NTPase.
 IPR015415; Vps4_C. 

Pfam

 PF00004; AAA
 PF02933; CDC48_2
 PF02359; CDC48_N
 PF09336; Vps4_C 

SMART

 SM00382; AAA
 SM01072; CDC48_2
 SM01073; CDC48_N 

PROSITE

 PS00674; AAA 

PRINTS