UniProt Accession

 XRCC5_HUMAN; P13010; A8K3X5; Q0Z7V0; Q4VBQ5; Q53HH7; Q7M4N0; Q9UCQ0; Q9UCQ1 

Genbank Protein ID

 J04977; M30938; AK290740; AK222603; DQ787434; CH471063; BC019027; BC095442; X57500 

Genbank Nucleotide ID

 AAA59475.1; AAA36154.1; BAF83429.1; BAD96323.1; ABG46942.1; EAW70562.1; AAH19027.1; AAH95442.1; CAA40736.1 

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	*MVRSGNKAAVVLCM	methylation	[1]
36	SPFEQAKKVITMFVQ	ubiquitination	[2, 3, 4, 5]
125	IQHETIGKKFEKRHI	ubiquitination	[6]
126	QHETIGKKFEKRHIE	ubiquitination	[4]
144	DLSSRFSKSQLDIII	acetylation	[7]
144	DLSSRFSKSQLDIII	ubiquitination	[2, 3, 4, 5, 6, 8, 9]
155	DIIIHSLKKCDISLQ	acetylation	[7, 9]
155	DIIIHSLKKCDISLQ	ubiquitination	[2, 4, 5, 6]
156	IIIHSLKKCDISLQF	ubiquitination	[4, 6, 9]
195	HGPSFPLKGITEQQK	acetylation	[7]
195	HGPSFPLKGITEQQK	ubiquitination	[2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13]
202	KGITEQQKEGLEIVK	ubiquitination	[2, 4, 5, 6, 9, 13]
233	SFSESLRKLCVFKKI	ubiquitination	[4, 6]
239	RKLCVFKKIERHSIH	ubiquitination	[4]
265	SIRIAAYKSILQERV	acetylation	[7, 9, 14, 15]
265	SIRIAAYKSILQERV	ubiquitination	[2, 3, 4, 5, 6, 9, 12, 13]
273	SILQERVKKTWTVVD	ubiquitination	[4, 9]
274	ILQERVKKTWTVVDA	ubiquitination	[3, 4, 6, 9]
282	TWTVVDAKTLKKEDI	acetylation	[15]
282	TWTVVDAKTLKKEDI	ubiquitination	[2, 4, 5, 6, 9, 13]
285	VVDAKTLKKEDIQKE	ubiquitination	[4]
286	VDAKTLKKEDIQKET	ubiquitination	[4]
307	DDETEVLKEDIIQGF	ubiquitination	[4, 6, 8, 9, 11, 12, 13, 16]
325	SDIVPFSKVDEEQMK	ubiquitination	[2, 3, 4, 5, 6, 8, 9, 11, 12, 13]
332	KVDEEQMKYKSEGKC	acetylation	[7, 9]
332	KVDEEQMKYKSEGKC	ubiquitination	[2, 4, 5, 6, 9, 13]
334	DEEQMKYKSEGKCFS	ubiquitination	[4, 12]
338	MKYKSEGKCFSVLGF	acetylation	[7, 9, 15]
338	MKYKSEGKCFSVLGF	ubiquitination	[2, 3, 4, 5, 6, 12]
347	FSVLGFCKSSQVQRR	ubiquitination	[4, 6, 9, 12]
363	FMGNQVLKVFAARDD	ubiquitination	[2, 3, 4, 5, 6, 8, 11, 12]
399	IVRYAYDKRANPQVG	ubiquitination	[4, 6]
439	QYMFSSLKNSKKYAP	ubiquitination	[2, 4, 5, 6, 13]
443	SSLKNSKKYAPTEAQ	ubiquitination	[2, 4, 5, 6, 9, 12, 13]
465	IDSMSLAKKDEKTDT	ubiquitination	[2, 5, 13]
466	DSMSLAKKDEKTDTL	ubiquitination	[4, 6, 9]
469	SLAKKDEKTDTLEDL	ubiquitination	[4, 6, 13]
481	EDLFPTTKIPNPRFQ	ubiquitination	[2, 3, 4, 5, 6, 8, 9, 11, 12, 13, 16]
525	PPAEVTTKSQIPLSK	ubiquitination	[4, 6, 9, 12]
532	KSQIPLSKIKTLFPL	acetylation	[7, 14]
532	KSQIPLSKIKTLFPL	ubiquitination	[2, 3, 4, 5, 6, 8, 9, 12, 13]
534	QIPLSKIKTLFPLIE	acetylation	[14]
534	QIPLSKIKTLFPLIE	ubiquitination	[2, 3, 4, 5, 6, 9, 12, 13]
543	LFPLIEAKKKDQVTA	acetylation	[14]
543	LFPLIEAKKKDQVTA	ubiquitination	[2, 4, 5, 6, 13]
544	FPLIEAKKKDQVTAQ	ubiquitination	[2, 3, 4, 9, 12]
545	PLIEAKKKDQVTAQE	ubiquitination	[2, 4, 5, 12]
565	HEDGPTAKKLKTEQG	acetylation	[9, 15]
565	HEDGPTAKKLKTEQG	ubiquitination	[6, 13]
648	AFREEAIKFSEEQRF	acetylation	[9]
648	AFREEAIKFSEEQRF	ubiquitination	[2, 3, 4, 5, 6]
660	QRFNNFLKALQEKVE	acetylation	[7]
660	QRFNNFLKALQEKVE	ubiquitination	[2, 3, 4, 5, 6, 9, 12, 13]
665	FLKALQEKVEIKQLN	acetylation	[7, 9]
665	FLKALQEKVEIKQLN	ubiquitination	[4, 6, 9]
702	SVTAEEAKKFLAPKD	acetylation	[9, 14, 15, 17]
702	SVTAEEAKKFLAPKD	ubiquitination	[6]
703	VTAEEAKKFLAPKDK	ubiquitination	[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

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