Gene: XRCC6 - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | XRCC6 | ||||||||||||||||
NCBI Gene ID | : | 2547 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | 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 | ATP-dependent DNA helicase II, 70 kDa subunit | CTA-216E10.7 | CTC box binding factor 75 kDa subunit | CTC box-binding factor 75 kDa subunit | CTC75 | CTCBF | D22S671 | D22S731 | DNA repair protein XRCC6 | G22P1 | Ku ANTIGEN, 70-KD SUBUNIT | Ku autoantigen p70 subunit | Ku autoantigen, 70kDa | KU70 | Ku70 | LUPUS AUTOANTIGEN p70 | lupus Ku autoantigen protein p70 | ML8 | thyroid autoantigen 70kD (Ku antigen) | thyroid autoantigen 70kDa (Ku antigen) | THYROID AUTOANTIGEN, 70-KD | THYROID-LUPUS AUTOANTIGEN | thyroid-lupus autoantigen p70 | TLAA | X-ray repair complementing defective repair in Chinese hamster cells 6 | X-ray repair cross-complementing protein 6 | X-RAY REPAIR, COMPLEMENTING DEFECTIVE, IN CHINESE HAMSTER, 6 | XRCC6 Source: GPSDB |
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Gene Homologs | : | AgaP_AGAP002690 (Anopheles gambiae) | cku-70 (Caenorhabditis elegans) | Irbp (Drosophila melanogaster) | KLLA0C06226g (Kluyveromyces lactis) | KU70 (Arabidopsis thaliana) | LOC100536337 (Danio rerio) | MGG_01512 (Magnaporthe oryzae) | NCU08290 (Neurospora crassa) | Os07g0184900 (Oryza sativa) | pku70 (Schizosaccharomyces pombe) | XRCC6 (Bos taurus) | XRCC6 (Canis lupus familiaris) | xrcc6 (Danio rerio) | XRCC6 (Gallus gallus) | XRCC6 (Homo sapiens) | XRCC6 (Macaca mulatta) | Xrcc6 (Mus musculus) | XRCC6 (Pan troglodytes) | Xrcc6 (Rattus norvegicus) | YKU70 (Saccharomyces cerevisiae) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_000036 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
---|---|---|---|---|---|
X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) | Homo sapiens | B1AHC8 (UniProtKB/TrEMBL) | B1AHC8_HUMAN (UniProtKB/TrEMBL) | View | |
X-ray repair cross-complementing protein 6 | Homo sapiens | P12956 (UniProtKB/Swiss-Prot) | XRCC6_HUMAN (UniProtKB/Swiss-Prot) | 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. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
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1 | OB_009819 | Homo sapiens |
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Like its counterpart XRCC5, XRCC6 is a helicase involved in DNA repair and chromatin remodelling [0579]. Also called Ku70, XRCC6 has been linked to the telomeres [0158], WRN [0983], and other genes putatively regulating ageing. Mice with mutations in XRCC6 and XRCC5 exhibit signs of early ageing with low cancer levels, yet since XRCC5 mutants exhibit a similar phenotype the involvement of XRCC6 in the ageing phenotype is not clear in spite of some early signs of ageing in XRCC6 mutants [1906]. It is possible that XRCC6 is involved in ageing, though further results are necessary to determine whether it plays a role in human ageing. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
Sequences
B1AHC8_HUMAN | B1AHC8 | X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) (Homo sapiens) from UniProtKB/TrEMBL Length: 568 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 560 B1AHC8_HUMAN 1 MSGWESYYKTEGDEEAEEEQEENLEASGDYKYSGRDSLIFLVDASKAMFESQSEDELTPFDMSIQELDNPGAKRILELDQFKGQQGQKRFQDMMGHGSDYSLSEVLWVCANLFSDVQFKMSHKRIMLFTNEDNPHGNDSAKASRARTKAGDLRDTGIFLDLMHLKKPGGFDISLFYRDIISIAEDEDLRVHFEESSKLEDLLRKVRAKETRKRALSRLKLKLNKDIVISVGIYNLVQKALKPPPIKLYRETNEPVKTKTRTFNTSTGGLLLPSDTKRSQIYGSRQIILEKEETEELKRFDDPGLMLMGFKPLVLLKKHHYLRPSLFVYPEESLVIGSSTLFSALLIKCLEKEVAALCRYTPRRNIPPYFVALVPQEEELDDQKIQVTPPGFQLVFLPFADDKRKMPFTEKIMATPEQVGKMKAIVEKLRFTYRSDSFENPVLQQHFRNLEALALDLMEPEQAVDLTLPKVEAMNKRLGSLVDEFKELVYPPDYNPEGKVTKRKHDNEGSGSKRPKVEYSEEELKTHISKGTLGKFTVPMLKEACRAYGLKSGLKKQELLEALTKHFQD 568
XRCC6_HUMAN | P12956 | X-ray repair cross-complementing protein 6 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 609 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 560 570 580 590 600 XRCC6_HUMAN 1 MSGWESYYKTEGDEEAEEEQEENLEASGDYKYSGRDSLIFLVDASKAMFESQSEDELTPFDMSIQCIQSVYISKIISSDRDLLAVVFYGTEKDKNSVNFKNIYVLQELDNPGAKRILELDQFKGQQGQKRFQDMMGHGSDYSLSEVLWVCANLFSDVQFKMSHKRIMLFTNEDNPHGNDSAKASRARTKAGDLRDTGIFLDLMHLKKPGGFDISLFYRDIISIAEDEDLRVHFEESSKLEDLLRKVRAKETRKRALSRLKLKLNKDIVISVGIYNLVQKALKPPPIKLYRETNEPVKTKTRTFNTSTGGLLLPSDTKRSQIYGSRQIILEKEETEELKRFDDPGLMLMGFKPLVLLKKHHYLRPSLFVYPEESLVIGSSTLFSALLIKCLEKEVAALCRYTPRRNIPPYFVALVPQEEELDDQKIQVTPPGFQLVFLPFADDKRKMPFTEKIMATPEQVGKMKAIVEKLRFTYRSDSFENPVLQQHFRNLEALALDLMEPEQAVDLTLPKVEAMNKRLGSLVDEFKELVYPPDYNPEGKVTKRKHDNEGSGSKRPKVEYSEEELKTHISKGTLGKFTVPMLKEACRAYGLKSGLKKQELLEALTKHFQD 609
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Reeves WH, Sthoeger ZM:
Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen.
J Biol Chem. 1989; 264: 5047-52.
PubMed (ID: 2466842)
MeSH Terms: Antigens, Nuclear; Antigens, Surface/genetics; Autoantigens/genetics; DNA Helicases; DNA-Binding Proteins/genetics; DNA/isolation & purification; Lupus Erythematosus, Systemic/genetics - Chai W, Ford LP, Lenertz L, Wright WE, Shay JW:
Human Ku70/80 associates physically with telomerase through interaction with hTERT.
J Biol Chem. 2002; 277: 47242-7.
PubMed (ID: 12377759), doi:10.1074/jbc.M208542200
MeSH Terms: Antigens, Nuclear; DNA Helicases; DNA-Binding Proteins/metabolism; Nuclear Proteins/metabolism; Telomerase/metabolism - Sawada M, Sun W, Hayes P, Leskov K, Boothman DA, Matsuyama S:
Ku70 suppresses the apoptotic translocation of Bax to mitochondria.
Nat Cell Biol. 2003; 5: 320-9.
PubMed (ID: 12652308), doi:10.1038/ncb950
MeSH Terms: Apoptosis/physiology; Arabidopsis Proteins/metabolism; DNA-Binding Proteins/metabolism; Eukaryotic Cells/metabolism; Mitochondria/metabolism; Protein Transport/physiology; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins/deficiency - Um JH, Kim SJ, Kim DW, Ha MY, Jang JH, Kim DW, Chung BS, Kang CD, Kim SH:
Tissue-specific changes of DNA repair protein Ku and mtHSP70 in aging rats and their retardation by caloric restriction.
Mech Ageing Dev. 2003; 124: 967-75.
PubMed (ID: 14499502)
MeSH Terms: Aging/metabolism; Antigens, Nuclear/metabolism; Caloric Restriction; DNA-Binding Proteins/metabolism; HSP70 Heat-Shock Proteins/metabolism - Li B, Navarro S, Kasahara N, Comai L:
Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1.
J Biol Chem. 2004; 279: 13659-67.
PubMed (ID: 14734561), doi:10.1074/jbc.M311606200
MeSH Terms: Antigens, Nuclear/metabolism; DNA Helicases/metabolism; DNA-Binding Proteins/metabolism; Poly(ADP-ribose) Polymerases/metabolism; Werner Syndrome/metabolism - Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA:
Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.
Mol Cell. 2004; 13: 627-38.
PubMed (ID: 15023334)
MeSH Terms: Acetyltransferases/metabolism; Antigens, Nuclear/metabolism; Apoptosis/physiology; DNA Helicases; DNA-Binding Proteins/metabolism; Nuclear Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins/metabolism; Trans-Activators/metabolism; Tumor Suppressor Proteins/metabolism - Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA:
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase.
Science. 2004; 305: 390-2.
PubMed (ID: 15205477), doi:10.1126/science.1099196
MeSH Terms: Apoptosis; Caloric Restriction; Cell Survival; Histone Deacetylases/metabolism; Proto-Oncogene Proteins c-bcl-2; Sirtuins/metabolism - Comai L, Li B:
The Werner syndrome protein at the crossroads of DNA repair and apoptosis.
Mech Ageing Dev. 2004; 125: 521-8.
PubMed (ID: 15336909), doi:10.1016/j.mad.2004.06.004
MeSH Terms: Apoptosis/genetics; Carrier Proteins/genetics; DNA Repair/genetics; DNA-Binding Proteins/genetics; Werner Syndrome/genetics - McColl G, Vantipalli MC, Lithgow GJ:
The C. elegans ortholog of mammalian Ku70, interacts with insulin-like signaling to modulate stress resistance and life span.
FASEB J. 2005; 19: 1716-8.
PubMed (ID: 16099946), PubMed Central (ID: PMC1400606), doi:10.1096/fj.04-2447fje
MeSH Terms: Antigens, Nuclear/physiology; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Insulin/metabolism; Longevity - Li H, Vogel H, Holcomb VB, Gu Y, Hasty P:
Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer.
Mol Cell Biol. 2007; 27: 8205-14.
PubMed (ID: 17875923), PubMed Central (ID: PMC2169178), doi:10.1128/MCB.00785-07
MeSH Terms: Aging, Premature/genetics; Antigens, Nuclear/genetics; DNA-Binding Proteins/genetics; Gene Deletion; Neoplasms/pathology - Li H, Choi YJ, Hanes MA, Marple T, Vogel H, Hasty P:
Deleting Ku70 is milder than deleting Ku80 in p53-mutant mice and cells.
Oncogene. 2009; 28: 1875-8.
PubMed (ID: 19330025), doi:10.1038/onc.2009.57
MeSH Terms: Antigens, Nuclear/genetics; DNA-Binding Proteins/genetics; Genes, p53; Mutation - Salminen A, Helenius M, Lahtinen T, Korhonen P, Tapiola T, Soininen H, Solovyan V:
Down-regulation of Ku autoantigen, DNA-dependent protein kinase, and poly(ADP-ribose) polymerase during cellular senescence.
Biochem Biophys Res Commun. 1997; 238: 712-6.
PubMed (ID: 9325154), doi:10.1006/bbrc.1997.7371
MeSH Terms: Antigens, Nuclear; Autoantigens/metabolism; DNA Helicases; DNA-Binding Proteins/metabolism; Down-Regulation/physiology; Nuclear Proteins/metabolism; Poly(ADP-ribose) Polymerases/metabolism; Protein-Serine-Threonine Kinases/metabolism - Li GC, Ouyang H, Li X, Nagasawa H, Little JB, Chen DJ, Ling CC, Fuks Z, Cordon-Cardo C:
Ku70: a candidate tumor suppressor gene for murine T cell lymphoma.
Mol Cell. 1998; 2: 1-8.
PubMed (ID: 9702186)
MeSH Terms: Antigens, Nuclear; DNA Helicases; DNA-Binding Proteins/genetics; Genes, Tumor Suppressor; Lymphoma, T-Cell/genetics; Nuclear Proteins/genetics; Protein-Serine-Threonine Kinases/genetics - Li B, Comai L:
Functional interaction between Ku and the werner syndrome protein in DNA end processing.
J Biol Chem. 2000; 275: 28349-52.
PubMed (ID: 10880505), doi:10.1074/jbc.C000289200
MeSH Terms: Antigens, Nuclear; DNA Damage; DNA Helicases/physiology; DNA Repair; DNA-Binding Proteins/physiology; Nuclear Proteins/physiology - Li B, Comai L:
Requirements for the nucleolytic processing of DNA ends by the Werner syndrome protein-Ku70/80 complex.
J Biol Chem. 2001; 276: 9896-902.
PubMed (ID: 11152456), doi:10.1074/jbc.M008575200
MeSH Terms: Antigens, Nuclear; Cell Nucleus/metabolism; DNA Helicases/metabolism; DNA-Binding Proteins/metabolism; DNA/metabolism; Nuclear Proteins/metabolism; Werner Syndrome/genetics - Schild-Poulter C, Pope L, Giffin W, Kochan JC, Ngsee JK, Traykova-Andonova M, Haché RJ:
The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase.
J Biol Chem. 2001; 276: 16848-56.
PubMed (ID: 11279128), doi:10.1074/jbc.M100768200
MeSH Terms: Antigens, Nuclear; DNA Helicases; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Homeodomain Proteins/metabolism; Nuclear Proteins/metabolism; Protein-Serine-Threonine Kinases/metabolism; Saccharomyces cerevisiae Proteins; Transcription, Genetic - Shen J, Loeb LA:
Unwinding the molecular basis of the Werner syndrome.
Mech Ageing Dev. 2001; 122: 921-44.
PubMed (ID: 11348659)
MeSH Terms: DNA Helicases/physiology; DNA-Binding Proteins; Werner Syndrome/enzymology - Walker JR, Corpina RA, Goldberg J:
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.
Nature. 2001; 412: 607-14.
PubMed (ID: 11493912), doi:10.1038/35088000
MeSH Terms: Antigens, Nuclear; DNA Helicases; DNA Repair; DNA-Binding Proteins/chemistry; DNA/metabolism; Nuclear Proteins/chemistry - Li B, Comai L:
Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein.
Nucleic Acids Res. 2002; 30: 3653-61.
PubMed (ID: 12202749), PubMed Central (ID: PMC137412)
MeSH Terms: Antigens, Nuclear; DNA Helicases; Protein-Serine-Threonine Kinases/metabolism
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot
- UniProtKB/TrEMBL