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Ku70 (XRCC6)

Protein FULL name:

X-ray repair cross-complementing protein 6, 5'-deoxyribose-5-phosphate lyase Ku70, X-ray repair complementing defective repair in Chinese hamster cells 6, ATP-dependent DNA helicase 2 subunit1, ATP-dependent DNA helicase II 70kDa subunit, Lupus Ku autoantigen protein p70, 70kDa subunit of Ku antigen, Thyroid-lupus autoantigen, CTC box-binding factor 75 kDa subunit, DNA repair protein XRCC6


Protein SHORT name:

5'-dRP lyase Ku70, Ku70, TLAA, CTCBF, CTC75, XRCC6


Ku70 (XRCC6) (Homo sapiens) is product of expression of XRCC6 gene.


Ku70 (XRCC6) is involved in:

NHEJ in Homo sapiens
     


Keywords:



FUNCTION: 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.

SUBUNIT: Heterodimer of a 70 kDa (XRCC6) and a 80 kDa (XRCC5) subunit. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex. The dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression. In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5. Interacts with ELF3. Interacts with XRCC6BP1.

INTERACTION: Q96P48:ARAP1; NbExp=1; IntAct=EBI-353208, EBI-710003; Q99728:BARD1; NbExp=1; IntAct=EBI-353208, EBI-473181; P42858:HTT; NbExp=1; IntAct=EBI-353208, EBI-466029; Q92597:NDRG1; NbExp=2; IntAct=EBI-353208, EBI-716486; Q9NQB0:TCF7L2; NbExp=3; IntAct=EBI-353208, EBI-924724; P04637:TP53; NbExp=1; IntAct=EBI-353208, EBI-366083; P13010:XRCC5; NbExp=1; IntAct=EBI-353208, EBI-357997;

SUBCELLULAR LOCATION: Nucleus.

DEVELOPMENTAL STAGE: Expression does not increase during promyelocyte differentiation.

INDUCTION: In osteoblasts, by FGF2.

PTM: Phosphorylation by PRKDC may enhance helicase activity. Phosphorylation of Ser-51 does not affect DNA repair.

MISCELLANEOUS: Individuals with systemic lupus erythematosus (SLE) and related disorders produce extremely large amounts of autoantibodies to XRCC5 and XRCC6. Existence of a major autoantigenic epitope or epitopes on the C-terminal 190 amino acids of XRCC6 containing the leucine repeat. The majority of autoantibodies to XRCC6 in most sera from patients with SLE seem to be reactive with this region.

SIMILARITY: Belongs to the ku70 family.

SIMILARITY: Contains 1 Ku domain.

SIMILARITY: Contains 1 SAP domain.

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 125729
4503841
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P12956 P12956
PFAM: PF02735
PF03730
PF03731
PF02037
PF02735
PF03730
PF03731
PF02037
InterPro: IPR006164
IPR006165
IPR005160
IPR005161
IPR003034
IPR016194
IPR006164
IPR006165
IPR005160
IPR005161
IPR003034
IPR016194
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MSGWESYYKTEGDEEAEEEQEENLEASGDYKYSGRDSLIFLVDASKAMFE
SQSEDELTPFDMSIQCIQSVYISKIISSDRDLLAVVFYGTEKDKNSVNFK
NIYVLQELDNPGAKRILELDQFKGQQGQKRFQDMMGHGSDYSLSEVLWVC
ANLFSDVQFKMSHKRIMLFTNEDNPHGNDSAKASRARTKAGDLRDTGIFL
DLMHLKKPGGFDISLFYRDIISIAEDEDLRVHFEESSKLEDLLRKVRAKE
TRKRALSRLKLKLNKDIVISVGIYNLVQKALKPPPIKLYRETNEPVKTKT
RTFNTSTGGLLLPSDTKRSQIYGSRQIILEKEETEELKRFDDPGLMLMGF
KPLVLLKKHHYLRPSLFVYPEESLVIGSSTLFSALLIKCLEKEVAALCRY
TPRRNIPPYFVALVPQEEELDDQKIQVTPPGFQLVFLPFADDKRKMPFTE
KIMATPEQVGKMKAIVEKLRFTYRSDSFENPVLQQHFRNLEALALDLMEP
EQAVDLTLPKVEAMNKRLGSLVDEFKELVYPPDYNPEGKVTKRKHDNEGS
GSKRPKVEYSEEELKTHISKGTLGKFTVPMLKEACRAYGLKSGLKKQELL
EALTKHFQD

Ku70 (XRCC6) (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Cloning and characterization of a cDNA that encodes a 70-kDa novel human thyroid autoantigen. Chan JY, Lerman MI, Prabhakar BS, Isozaki O, Santisteban P, Kuppers RC, Oates EL, Notkins AL, Kohn LD J Biol Chem March 5, 1989
Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. Reeves WH, Sthoeger ZM J Biol Chem March 25, 1989
Identification of proteins binding to interferon-inducible transcriptional enhancers in hematopoietic cells. Wedrychowski A, Henzel W, Huston L, Paslidis N, Ellerson D, McRae M, Seong D, Howard OM, Deisseroth A J Biol Chem March 5, 1992
Nucleotide sequence and genomic structure analyses of the p70 subunit of the human Ku autoantigen: evidence for a family of genes encoding Ku (p70)-related polypeptides. Griffith AJ, Craft J, Evans J, Mimori T, Hardin JA Mol Biol Rep May 1, 1992
Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simoncsits A, Susic S, Rahman K, Marusic L, Chen J, et al. EMBO J Oct. 17, 1994
Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen. Genersch E, Eckerskorn C, Lottspeich F, Herzog C, Kuhn K, Poschl E EMBO J Jan. 15, 1995
Non-histone protein 1 (NHP1) is a member of the Ku protein family which is upregulated in differentiating mouse myoblasts and human promyelocytes. Oderwald H, Hughes MJ, Jost JP FEBS Lett March 18, 1996
Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions. Jin S, Weaver DT EMBO J Nov. 17, 1997
Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. West RB, Yaneva M, Lieber MR Mol Cell Biol Oct. 1, 1998
DNA-dependent protein kinase phosphorylation sites in Ku 70/80 heterodimer. Chan DW, Ye R, Veillette CJ, Lees-Miller SP Biochemistry Jan. 9, 1999
Ku, a DNA repair protein with multiple cellular functions? Featherstone C, Jackson SP Mutat Res May 14, 1999
Isolation of Ku70-binding proteins (KUBs). Yang CR, Yeh S, Leskov K, Odegaard E, Hsu HL, Chang C, Kinsella TJ, Chen DJ, Boothman DA Nucleic Acids Res May 15, 1999
The DNA sequence of human chromosome 22. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al. Nature Dec. 2, 1999
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Walker JR, Corpina RA, Goldberg J Nature Aug. 9, 2001
The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70. Zhang Z, Zhu L, Lin D, Chen F, Chen DJ, Chen Y J Biol Chem Oct. 12, 2001
Defining interactions between DNA-PK and ligase IV/XRCC4. Hsu HL, Yannone SM, Chen DJ DNA Repair (Amst) March 28, 2002
Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA J Biol Chem Oct. 4, 2002
Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. Calsou P, Delteil C, Frit P, Drouet J, Salles B J Mol Biol Jan. 7, 2003
Positive and negative modulation of the transcriptional activity of the ETS factor ESE-1 through interaction with p300, CREB-binding protein, and Ku 70/86. Wang H, Fang R, Cho JY, Libermann TA, Oettgen P J Biol Chem June 11, 2004
Large-scale characterization of HeLa cell nuclear phosphoproteins. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP Proc Natl Acad Sci U S A Aug. 17, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC. Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M, Vandekerckhove J Proteomics Sept. 1, 2005
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal Jan. 1, 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem June 1, 2009
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 Aug. 14, 2009
Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA Nature April 22, 2010


Last modification of this entry: Oct. 12, 2010.

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