UniProt Accession

 XRCC6_HUMAN; P12956; Q6FG89; Q9UCQ2; Q9UCQ3 

Genbank Protein ID

 J04607; J04611; M32865; S38729; CR542219; AY870329; Z83840; BC008343; BC010034; BC012154; BC018259; BC072449 

Genbank Nucleotide ID

 AAA61177.1; AAA51733.1; AAA36155.1; AAB22381.1; CAG47015.1; AAW34364.1; CAB46206.1; AAH08343.1; AAH10034.1; AAH12154.1; AAH18259.1; AAH72449.1 

Protein Name

 X-ray repair cross-complementing protein 6 

Protein Synonyms/Alias

 5'-deoxyribose-5-phosphate lyase Ku70; 5'-dRP lyase Ku70; 70 kDa subunit of Ku antigen; ATP-dependent DNA helicase 2 subunit 1; ATP-dependent DNA helicase II 70 kDa subunit; CTC box-binding factor 75 kDa subunit; CTC75; CTCBF; DNA repair protein XRCC6; Lupus Ku autoantigen protein p70; Ku70; Thyroid-lupus autoantigen; TLAA; X-ray repair complementing defective repair in Chinese hamster cells 6 

Gene Name

 XRCC6 

Gene Synonyms/Alias

 G22P1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
31	LEASGDYKYSGRDSL	acetylation	[1]
31	LEASGDYKYSGRDSL	ubiquitination	[2, 3]
92	VVFYGTEKDKNSVNF	ubiquitination	[2]
94	FYGTEKDKNSVNFKN	ubiquitination	[2]
100	DKNSVNFKNIYVLQE	ubiquitination	[2, 3, 4, 5, 6, 7]
114	ELDNPGAKRILELDQ	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10]
123	ILELDQFKGQQGQKR	ubiquitination	[2, 4, 6, 7, 10]
129	FKGQQGQKRFQDMMG	ubiquitination	[6]
182	PHGNDSAKASRARTK	ubiquitination	[2, 3, 6, 10]
189	KASRARTKAGDLRDT	ubiquitination	[2, 6]
206	FLDLMHLKKPGGFDI	ubiquitination	[4, 7]
207	LDLMHLKKPGGFDIS	ubiquitination	[6]
238	VHFEESSKLEDLLRK	acetylation	[11]
238	VHFEESSKLEDLLRK	ubiquitination	[2, 4, 7]
282	NLVQKALKPPPIKLY	ubiquitination	[2, 6]
287	ALKPPPIKLYRETNE	ubiquitination	[4, 5, 6, 7]
297	RETNEPVKTKTRTFN	ubiquitination	[2]
317	LLLPSDTKRSQIYGS	acetylation	[12]
317	LLLPSDTKRSQIYGS	ubiquitination	[2, 3, 4, 5, 6, 7, 10, 13]
331	SRQIILEKEETEELK	acetylation	[1, 12]
331	SRQIILEKEETEELK	ubiquitination	[2, 6]
338	KEETEELKRFDDPGL	acetylation	[1, 12]
338	KEETEELKRFDDPGL	ubiquitination	[2, 3, 6]
351	GLMLMGFKPLVLLKK	ubiquitination	[2, 3, 4, 6, 7]
357	FKPLVLLKKHHYLRP	ubiquitination	[2, 3, 4, 6, 7]
358	KPLVLLKKHHYLRPS	ubiquitination	[6]
392	LLIKCLEKEVAALCR	ubiquitination	[6]
443	FLPFADDKRKMPFTE	ubiquitination	[2, 3, 4, 6, 7]
445	PFADDKRKMPFTEKI	ubiquitination	[4, 6, 7]
451	RKMPFTEKIMATPEQ	ubiquitination	[2, 3, 4, 5, 6, 7]
461	ATPEQVGKMKAIVEK	acetylation	[1]
461	ATPEQVGKMKAIVEK	ubiquitination	[2, 3, 6]
468	KMKAIVEKLRFTYRS	acetylation	[1]
468	KMKAIVEKLRFTYRS	ubiquitination	[2, 6]
516	PKVEAMNKRLGSLVD	ubiquitination	[2]
526	GSLVDEFKELVYPPD	ubiquitination	[2, 3, 6]
539	PDYNPEGKVTKRKHD	acetylation	[12]
539	PDYNPEGKVTKRKHD	ubiquitination	[2, 6]
542	NPEGKVTKRKHDNEG	acetylation	[12]
542	NPEGKVTKRKHDNEG	ubiquitination	[6]
544	EGKVTKRKHDNEGSG	acetylation	[12]
553	DNEGSGSKRPKVEYS	acetylation	[12]
553	DNEGSGSKRPKVEYS	ubiquitination	[2]
556	GSGSKRPKVEYSEEE	acetylation	[12]
556	GSGSKRPKVEYSEEE	sumoylation	[14]
556	GSGSKRPKVEYSEEE	ubiquitination	[2, 3, 6]
565	EYSEEELKTHISKGT	ubiquitination	[2, 4, 5, 6, 7]
570	ELKTHISKGTLGKFT	ubiquitination	[6]
575	ISKGTLGKFTVPMLK	ubiquitination	[2, 3, 4, 5, 6, 7]
582	KFTVPMLKEACRAYG	ubiquitination	[5, 6]
591	ACRAYGLKSGLKKQE	ubiquitination	[5, 6, 10]
595	YGLKSGLKKQELLEA	ubiquitination	[6]
596	GLKSGLKKQELLEAL	ubiquitination	[2, 6]
605	ELLEALTKHFQD***	ubiquitination	[2, 4, 5, 6, 7]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [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] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.
 Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA.
 Mol Cell. 2004 Mar 12;13(5):627-38. [PMID: 15023334]
 [13] 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]
 [14] Ku70 is stabilized by increased cellular SUMO.
 Yurchenko V, Xue Z, Gama V, Matsuyama S, Sadofsky MJ.
 Biochem Biophys Res Commun. 2008 Feb 1;366(1):263-8. [PMID: 18062920] 

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. Required for osteocalcin gene expression. 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. 5'-dRP lyase activity 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 261 468 Ku.
 DOMAIN 573 607 SAP.
 ACT_SITE 31 31 Schiff-base intermediate with DNA; for
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 6 6 Phosphoserine; by PRKDC.
 MOD_RES 31 31 N6-acetyllysine.
 MOD_RES 51 51 Phosphoserine; by PRKDC.
 MOD_RES 331 331 N6-acetyllysine.
 MOD_RES 338 338 N6-acetyllysine.
 MOD_RES 455 455 Phosphothreonine.
 MOD_RES 461 461 N6-acetyllysine.
 MOD_RES 477 477 Phosphoserine.
 MOD_RES 520 520 Phosphoserine.
 MOD_RES 550 550 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Activator; ATP-binding; Chromosome; Complete proteome; Direct protein sequencing; DNA damage; DNA recombination; DNA repair; DNA-binding; Helicase; Hydrolase; Lyase; Multifunctional enzyme; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Systemic lupus erythematosus; Transcription; Transcription regulation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 609 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:Compara.
 GO:0043564; C:Ku70:Ku80 complex; IDA:UniProtKB.
 GO:0016020; C:membrane; TAS:ProtInc.
 GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB.
 GO:0000783; C:nuclear telomere cap complex; TAS:BHF-UCL.
 GO:0005667; C:transcription factor complex; IDA:UniProtKB.
 GO:0051575; F:5'-deoxyribose-5-phosphate lyase activity; IMP:UniProtKB.
 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; IEA:InterPro.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0006266; P:DNA ligation; 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:0045892; P:negative regulation of transcription, DNA-dependent; IMP:UniProtKB.
 GO:0050769; P:positive regulation of neurogenesis; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0010212; P:response to ionizing radiation; IEA:Compara.
 GO:0000723; P:telomere maintenance; TAS:BHF-UCL.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0033151; P:V(D)J recombination; IEA:Compara. 

Interpro

 IPR006165; Ku70.
 IPR006164; Ku70/Ku80_beta-barrel_dom.
 IPR027388; Ku70_bridge/pillars_dom.
 IPR005160; Ku_C.
 IPR005161; Ku_N.
 IPR003034; SAP_dom.
 IPR016194; SPOC_like_C_dom.
 IPR002035; VWF_A. 

Pfam

 PF02735; Ku
 PF03730; Ku_C
 PF03731; Ku_N
 PF02037; SAP 

SMART

 SM00559; Ku78
 SM00513; SAP 

PROSITE

 PS50800; SAP 

PRINTS