CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008944
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
8MASGADSKGDDLSTAacetylation[1]
8MASGADSKGDDLSTAubiquitination[2, 3, 4, 5, 6, 7, 8]
18DLSTAILKQKNRPNRacetylation[1]
18DLSTAILKQKNRPNRubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
20STAILKQKNRPNRLIubiquitination[4, 6, 8, 11]
45VVSLSQPKMDELQLFubiquitination[6, 9, 10, 11]
60RGDTVLLKGKKRREAacetylation[1]
60RGDTVLLKGKKRREAubiquitination[4, 6, 11]
62DTVLLKGKKRREAVCacetylation[1]
63TVLLKGKKRREAVCIubiquitination[6]
81DDTCSDEKIRMNRVVacetylation[1]
81DDTCSDEKIRMNRVVubiquitination[6]
109IQPCPDVKYGKRIHVubiquitination[3, 4, 5, 6, 7, 9, 11, 12]
112CPDVKYGKRIHVLPIubiquitination[4, 6]
148EAYRPIRKGDIFLVRubiquitination[4, 5, 6]
164GMRAVEFKVVETDPSacetylation[1]
164GMRAVEFKVVETDPSubiquitination[6]
211DDIGGCRKQLAQIKEubiquitination[3, 6, 7, 8, 9, 10]
217RKQLAQIKEMVELPLubiquitination[3, 5, 6, 7, 8, 9, 10, 11, 12]
231LRHPALFKAIGVKPPubiquitination[3, 4, 5, 6, 7, 8, 9, 10, 11]
236LFKAIGVKPPRGILLubiquitination[4, 5, 6, 8, 9, 10, 11]
251YGPPGTGKTLIARAVacetylation[1]
251YGPPGTGKTLIARAVubiquitination[3, 4, 5, 6, 7, 8, 10, 11, 12]
288ESESNLRKAFEEAEKubiquitination[4, 6, 8, 9, 11]
295KAFEEAEKNAPAIIFubiquitination[6, 8, 9, 11]
312ELDAIAPKREKTHGEubiquitination[3, 4, 6, 7, 8, 9, 10, 11, 12]
315AIAPKREKTHGEVERacetylation[1]
315AIAPKREKTHGEVERmethylation[13]
336LTLMDGLKQRAHVIVacetylation[1]
336LTLMDGLKQRAHVIVubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15]
386EILQIHTKNMKLADDacetylation[1]
386EILQIHTKNMKLADDubiquitination[3, 4, 6, 7, 8, 9, 11]
389QIHTKNMKLADDVDLubiquitination[6, 8]
486IGGLEDVKRELQELVubiquitination[4, 6, 8, 9, 10, 11, 12, 14, 15]
502YPVEHPDKFLKFGMTubiquitination[3, 4, 6, 7, 8, 9, 10, 11, 12, 15]
505EHPDKFLKFGMTPSKacetylation[1, 16]
505EHPDKFLKFGMTPSKubiquitination[3, 4, 5, 6, 7, 8, 9, 10, 11]
512KFGMTPSKGVLFYGPacetylation[1]
512KFGMTPSKGVLFYGPubiquitination[4, 5, 6, 8, 9, 10, 14]
524YGPPGCGKTLLAKAIacetylation[1]
524YGPPGCGKTLLAKAIubiquitination[3, 4, 5, 6, 7, 8, 10, 12]
529CGKTLLAKAIANECQacetylation[1]
529CGKTLLAKAIANECQubiquitination[3, 4, 5, 6, 7, 8, 10, 11, 14, 15]
565NVREIFDKARQAAPCubiquitination[3, 6, 7]
584DELDSIAKARGGNIGubiquitination[4, 6, 8, 9, 14]
614EMDGMSTKKNVFIIGacetylation[1]
614EMDGMSTKKNVFIIGubiquitination[4, 6, 8, 9, 10, 11, 14]
615MDGMSTKKNVFIIGAacetylation[1]
615MDGMSTKKNVFIIGAubiquitination[6, 8, 10]
651YIPLPDEKSRVAILKacetylation[16]
651YIPLPDEKSRVAILKubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15]
658KSRVAILKANLRKSPacetylation[1]
658KSRVAILKANLRKSPubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14]
663ILKANLRKSPVAKDVacetylation[1]
663ILKANLRKSPVAKDVubiquitination[4, 9, 11]
668LRKSPVAKDVDLEFLacetylation[1, 16]
668LRKSPVAKDVDLEFLubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15]
677VDLEFLAKMTNGFSGacetylation[1]
696EICQRACKLAIRESIacetylation[1]
696EICQRACKLAIRESIubiquitination[3, 6, 7, 8, 10]
754VSDNDIRKYEMFAQTacetylation[1]
754VSDNDIRKYEMFAQTubiquitination[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
MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK 60
GKKRREAVCI VLSDDTCSDE KIRMNRVVRN NLRVRLGDVI SIQPCPDVKY GKRIHVLPID 120
DTVEGITGNL FEVYLKPYFL EAYRPIRKGD IFLVRGGMRA VEFKVVETDP SPYCIVAPDT 180
VIHCEGEPIK REDEEESLNE VGYDDIGGCR KQLAQIKEMV ELPLRHPALF KAIGVKPPRG 240
ILLYGPPGTG KTLIARAVAN ETGAFFFLIN GPEIMSKLAG ESESNLRKAF EEAEKNAPAI 300
IFIDELDAIA PKREKTHGEV ERRIVSQLLT LMDGLKQRAH VIVMAATNRP NSIDPALRRF 360
GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA NETHGHVGAD LAALCSEAAL 420
QAIRKKMDLI DLEDETIDAE VMNSLAVTMD DFRWALSQSN PSALRETVVE VPQVTWEDIG 480
GLEDVKRELQ ELVQYPVEHP DKFLKFGMTP SKGVLFYGPP GCGKTLLAKA IANECQANFI 540
SIKGPELLTM WFGESEANVR EIFDKARQAA PCVLFFDELD SIAKARGGNI GDGGGAADRV 600
INQILTEMDG MSTKKNVFII GATNRPDIID PAILRPGRLD QLIYIPLPDE KSRVAILKAN 660
LRKSPVAKDV DLEFLAKMTN GFSGADLTEI CQRACKLAIR ESIESEIRRE RERQTNPSAM 720
EVEEDDPVPE IRRDHFEEAM RFARRSVSDN DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG 780
AGPSQGSGGG TGGSVYTEDN DDDLYG 806 
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