CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004079
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 X-ray repair cross-complementing protein 5 
Protein Synonyms/Alias
 86 kDa subunit of Ku antigen; ATP-dependent DNA helicase 2 subunit 2; ATP-dependent DNA helicase II 80 kDa subunit; CTC box-binding factor 85 kDa subunit; CTC85; CTCBF; DNA repair protein XRCC5; Ku80; Ku86; Lupus Ku autoantigen protein p86; Nuclear factor IV; Thyroid-lupus autoantigen; TLAA; X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) 
Gene Name
 XRCC5 
Gene Synonyms/Alias
 G22P2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
7*MVRSGNKAAVVLCMmethylation[1]
36SPFEQAKKVITMFVQubiquitination[2, 3, 4, 5]
125IQHETIGKKFEKRHIubiquitination[6]
126QHETIGKKFEKRHIEubiquitination[4]
144DLSSRFSKSQLDIIIacetylation[7]
144DLSSRFSKSQLDIIIubiquitination[2, 3, 4, 5, 6, 8, 9]
155DIIIHSLKKCDISLQacetylation[7, 9]
155DIIIHSLKKCDISLQubiquitination[2, 4, 5, 6]
156IIIHSLKKCDISLQFubiquitination[4, 6, 9]
195HGPSFPLKGITEQQKacetylation[7]
195HGPSFPLKGITEQQKubiquitination[2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13]
202KGITEQQKEGLEIVKubiquitination[2, 4, 5, 6, 9, 13]
233SFSESLRKLCVFKKIubiquitination[4, 6]
239RKLCVFKKIERHSIHubiquitination[4]
265SIRIAAYKSILQERVacetylation[7, 9, 14, 15]
265SIRIAAYKSILQERVubiquitination[2, 3, 4, 5, 6, 9, 12, 13]
273SILQERVKKTWTVVDubiquitination[4, 9]
274ILQERVKKTWTVVDAubiquitination[3, 4, 6, 9]
282TWTVVDAKTLKKEDIacetylation[15]
282TWTVVDAKTLKKEDIubiquitination[2, 4, 5, 6, 9, 13]
285VVDAKTLKKEDIQKEubiquitination[4]
286VDAKTLKKEDIQKETubiquitination[4]
307DDETEVLKEDIIQGFubiquitination[4, 6, 8, 9, 11, 12, 13, 16]
325SDIVPFSKVDEEQMKubiquitination[2, 3, 4, 5, 6, 8, 9, 11, 12, 13]
332KVDEEQMKYKSEGKCacetylation[7, 9]
332KVDEEQMKYKSEGKCubiquitination[2, 4, 5, 6, 9, 13]
334DEEQMKYKSEGKCFSubiquitination[4, 12]
338MKYKSEGKCFSVLGFacetylation[7, 9, 15]
338MKYKSEGKCFSVLGFubiquitination[2, 3, 4, 5, 6, 12]
347FSVLGFCKSSQVQRRubiquitination[4, 6, 9, 12]
363FMGNQVLKVFAARDDubiquitination[2, 3, 4, 5, 6, 8, 11, 12]
399IVRYAYDKRANPQVGubiquitination[4, 6]
439QYMFSSLKNSKKYAPubiquitination[2, 4, 5, 6, 13]
443SSLKNSKKYAPTEAQubiquitination[2, 4, 5, 6, 9, 12, 13]
465IDSMSLAKKDEKTDTubiquitination[2, 5, 13]
466DSMSLAKKDEKTDTLubiquitination[4, 6, 9]
469SLAKKDEKTDTLEDLubiquitination[4, 6, 13]
481EDLFPTTKIPNPRFQubiquitination[2, 3, 4, 5, 6, 8, 9, 11, 12, 13, 16]
525PPAEVTTKSQIPLSKubiquitination[4, 6, 9, 12]
532KSQIPLSKIKTLFPLacetylation[7, 14]
532KSQIPLSKIKTLFPLubiquitination[2, 3, 4, 5, 6, 8, 9, 12, 13]
534QIPLSKIKTLFPLIEacetylation[14]
534QIPLSKIKTLFPLIEubiquitination[2, 3, 4, 5, 6, 9, 12, 13]
543LFPLIEAKKKDQVTAacetylation[14]
543LFPLIEAKKKDQVTAubiquitination[2, 4, 5, 6, 13]
544FPLIEAKKKDQVTAQubiquitination[2, 3, 4, 9, 12]
545PLIEAKKKDQVTAQEubiquitination[2, 4, 5, 12]
565HEDGPTAKKLKTEQGacetylation[9, 15]
565HEDGPTAKKLKTEQGubiquitination[6, 13]
648AFREEAIKFSEEQRFacetylation[9]
648AFREEAIKFSEEQRFubiquitination[2, 3, 4, 5, 6]
660QRFNNFLKALQEKVEacetylation[7]
660QRFNNFLKALQEKVEubiquitination[2, 3, 4, 5, 6, 9, 12, 13]
665FLKALQEKVEIKQLNacetylation[7, 9]
665FLKALQEKVEIKQLNubiquitination[4, 6, 9]
702SVTAEEAKKFLAPKDacetylation[9, 14, 15, 17]
702SVTAEEAKKFLAPKDubiquitination[6]
703VTAEEAKKFLAPKDKubiquitination[4, 9]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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]
 [13] 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]
 [14] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [15] 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]
 [16] 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]
 [17] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330
Functional Description
 Single stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. The XRCC5/6 dimer probably also acts as a 5'- deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. 
Sequence Annotation
 DOMAIN 251 460 Ku.
 REGION 138 165 Leucine-zipper.
 MOTIF 720 728 EEXXXDL motif.
 MOD_RES 144 144 N6-acetyllysine.
 MOD_RES 265 265 N6-acetyllysine.
 MOD_RES 332 332 N6-acetyllysine.
 MOD_RES 577 577 Phosphoserine; by PRKDC.
 MOD_RES 579 579 Phosphoserine; by PRKDC (Probable).
 MOD_RES 580 580 Phosphoserine; by PRKDC.
 MOD_RES 660 660 N6-acetyllysine.
 MOD_RES 665 665 N6-acetyllysine.
 MOD_RES 715 715 Phosphothreonine; by PRKDC (Probable).  
Keyword
 3D-structure; Acetylation; Activator; ATP-binding; Chromosome; Complete proteome; Direct protein sequencing; DNA damage; DNA recombination; DNA repair; DNA-binding; Helicase; Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Systemic lupus erythematosus; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 732 AA 
Protein Sequence
MVRSGNKAAV VLCMDVGFTM SNSIPGIESP FEQAKKVITM FVQRQVFAEN KDEIALVLFG 60
TDGTDNPLSG GDQYQNITVH RHLMLPDFDL LEDIESKIQP GSQQADFLDA LIVSMDVIQH 120
ETIGKKFEKR HIEIFTDLSS RFSKSQLDII IHSLKKCDIS LQFFLPFSLG KEDGSGDRGD 180
GPFRLGGHGP SFPLKGITEQ QKEGLEIVKM VMISLEGEDG LDEIYSFSES LRKLCVFKKI 240
ERHSIHWPCR LTIGSNLSIR IAAYKSILQE RVKKTWTVVD AKTLKKEDIQ KETVYCLNDD 300
DETEVLKEDI IQGFRYGSDI VPFSKVDEEQ MKYKSEGKCF SVLGFCKSSQ VQRRFFMGNQ 360
VLKVFAARDD EAAAVALSSL IHALDDLDMV AIVRYAYDKR ANPQVGVAFP HIKHNYECLV 420
YVQLPFMEDL RQYMFSSLKN SKKYAPTEAQ LNAVDALIDS MSLAKKDEKT DTLEDLFPTT 480
KIPNPRFQRL FQCLLHRALH PREPLPPIQQ HIWNMLNPPA EVTTKSQIPL SKIKTLFPLI 540
EAKKKDQVTA QEIFQDNHED GPTAKKLKTE QGGAHFSVSS LAEGSVTSVG SVNPAENFRV 600
LVKQKKASFE EASNQLINHI EQFLDTNETP YFMKSIDCIR AFREEAIKFS EEQRFNNFLK 660
ALQEKVEIKQ LNHFWEIVVQ DGITLITKEE ASGSSVTAEE AKKFLAPKDK PSGDTAAVFE 720
EGGDVDDLLD MI 732 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:Compara.
 GO:0043564; C:Ku70:Ku80 complex; IDA:UniProtKB.
 GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB.
 GO:0000783; C:nuclear telomere cap complex; TAS:BHF-UCL.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004003; F:ATP-dependent DNA helicase activity; TAS:ProtInc.
 GO:0003684; F:damaged DNA binding; IEA:InterPro.
 GO:0003690; F:double-stranded DNA binding; TAS:ProtInc.
 GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0006310; P:DNA recombination; TAS:ProtInc.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
 GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
 GO:0060218; P:hematopoietic stem cell differentiation; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IMP:UniProtKB.
 GO:0050769; P:positive regulation of neurogenesis; IEA:Compara.
 GO:0000723; P:telomere maintenance; TAS:BHF-UCL.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR006164; Ku70/Ku80_beta-barrel_dom.
 IPR024193; Ku80.
 IPR005160; Ku_C.
 IPR005161; Ku_N.
 IPR014893; Ku_PK_bind.
 IPR016194; SPOC_like_C_dom.
 IPR002035; VWF_A. 
Pfam
 PF02735; Ku
 PF03730; Ku_C
 PF03731; Ku_N
 PF08785; Ku_PK_bind 
SMART
 SM00559; Ku78
 SM00327; VWA 
PROSITE
  
PRINTS