ID:XRCC6_HUMAN DESCRIPTION: RecName: Full=X-ray repair cross-complementing protein 6; EC=3.6.4.-; EC=4.2.99.-; AltName: Full=5'-deoxyribose-5-phosphate lyase Ku70; Short=5'-dRP lyase Ku70; AltName: Full=70 kDa subunit of Ku antigen; AltName: Full=ATP-dependent DNA helicase 2 subunit 1; AltName: Full=ATP-dependent DNA helicase II 70 kDa subunit; AltName: Full=CTC box-binding factor 75 kDa subunit; Short=CTC75; Short=CTCBF; AltName: Full=DNA repair protein XRCC6; AltName: Full=Lupus Ku autoantigen protein p70; Short=Ku70; AltName: Full=Thyroid-lupus autoantigen; Short=TLAA; AltName: Full=X-ray repair complementing defective repair in Chinese hamster cells 6; 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. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. 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. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1. Interacts with CLU (By similarity). Binds to CDK9 isoform 2. INTERACTION: Q96P48:ARAP1; NbExp=2; IntAct=EBI-353208, EBI-710003; Q07812:BAX; NbExp=2; IntAct=EBI-353208, EBI-516580; P42858:HTT; NbExp=3; IntAct=EBI-353208, EBI-466029; Q92597:NDRG1; NbExp=2; IntAct=EBI-353208, EBI-716486; P78527:PRKDC; NbExp=5; IntAct=EBI-353208, EBI-352053; Q96EB6:SIRT1; NbExp=7; IntAct=EBI-353208, EBI-1802965; Q9NQB0:TCF7L2; NbExp=9; IntAct=EBI-353208, EBI-924724; P04637:TP53; NbExp=2; IntAct=EBI-353208, EBI-366083; Q14191:WRN; NbExp=7; IntAct=EBI-353208, EBI-368417; P13010:XRCC5; NbExp=8; IntAct=EBI-353208, EBI-357997; SUBCELLULAR LOCATION: Nucleus. Chromosome. 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; URL="http://egp.gs.washington.edu/data/g22p1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12956
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000723 telomere maintenance GO:0002218 activation of innate immune response GO:0002376 immune system process GO:0006266 DNA ligation GO:0006281 DNA repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006974 cellular response to DNA damage stimulus GO:0007420 brain development GO:0008152 metabolic process GO:0032481 positive regulation of type I interferon production GO:0032508 DNA duplex unwinding GO:0043312 neutrophil degranulation GO:0045087 innate immune response GO:0045860 positive regulation of protein kinase activity GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048660 regulation of smooth muscle cell proliferation GO:0051290 protein heterotetramerization GO:0071475 cellular hyperosmotic salinity response GO:0071480 cellular response to gamma radiation GO:0071481 cellular response to X-ray GO:0075713 establishment of integrated proviral latency GO:0097680 double-strand break repair via classical nonhomologous end joining
AK315618 - Homo sapiens cDNA, FLJ96699, highly similar to Homo sapiens thyroid autoantigen 70kDa (Ku antigen) (G22P1), mRNA. AK055786 - Homo sapiens cDNA FLJ31224 fis, clone KIDNE2004305, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC 3.6.1.-). AK304580 - Homo sapiens cDNA FLJ54993 complete cds, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC 3.6.1.-). AK293439 - Homo sapiens cDNA FLJ53970 complete cds, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC3.6.1.-). BC010034 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:19717 IMAGE:3536083), complete cds. BC018259 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:17453 IMAGE:3448510), complete cds. J04611 - Human lupus p70 (Ku) autoantigen protein mRNA, complete cds. BC008343 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:15860 IMAGE:3509801), complete cds. CR456492 - Homo sapiens G22P1 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.G22P1.V2). BC072449 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:87834 IMAGE:6167735), complete cds. BC012154 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:20380 IMAGE:4561541), complete cds. M32865 - Human Ku protein subunit mRNA, complete cds. S38729 - Ku autoantigen p70 subunit [human, mRNA, 2123 nt]. J04607 - Human thyroid autoantigen mRNA, complete cds. EU446892 - Synthetic construct Homo sapiens clone IMAGE:100070056; IMAGE:100012101; FLH257162.01L X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) (XRCC6) gene, encodes complete protein. EU831572 - Synthetic construct Homo sapiens clone HAIB:100066601; DKFZo004H0318 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) protein (XRCC6) gene, encodes complete protein. EU831485 - Synthetic construct Homo sapiens clone HAIB:100066514; DKFZo008H0317 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) protein (XRCC6) gene, encodes complete protein. JD052967 - Sequence 33991 from Patent EP1572962. CU676222 - Synthetic construct Homo sapiens gateway clone IMAGE:100019936 5' read XRCC6 mRNA. CU680242 - Synthetic construct Homo sapiens gateway clone IMAGE:100017426 5' read XRCC6 mRNA. AB385096 - Synthetic construct DNA, clone: pF1KB5432, Homo sapiens XRCC6 gene for ATP-dependent DNA helicase 2 subunit 1, complete cds, without stop codon, in Flexi system. CU013377 - Homo sapiens XRCC6, mRNA (cDNA clone IMAGE:100000252), complete cds, without stop codon, in Gateway system. CU013089 - Homo sapiens XRCC6, mRNA (cDNA clone IMAGE:100000348), complete cds, with stop codon, in Gateway system. KJ891210 - Synthetic construct Homo sapiens clone ccsbBroadEn_00604 XRCC6 gene, encodes complete protein. KJ896842 - Synthetic construct Homo sapiens clone ccsbBroadEn_06236 XRCC6 gene, encodes complete protein. CR542219 - Homo sapiens full open reading frame cDNA clone RZPDo834D0725D for gene G22P1, thyroid autoantigen 70kDa (Ku antigen); complete cds, incl. stopcodon. BC001583 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone IMAGE:3460998). DQ570184 - Homo sapiens piRNA piR-30296, complete sequence. AF052148 - Homo sapiens clone 24507 mRNA sequence. DQ588804 - Homo sapiens piRNA piR-55916, complete sequence. JD023268 - Sequence 4292 from Patent EP1572962. JD035977 - Sequence 17001 from Patent EP1572962. JD555240 - Sequence 536264 from Patent EP1572962. JD455474 - Sequence 436498 from Patent EP1572962. JD428234 - Sequence 409258 from Patent EP1572962. JD293044 - Sequence 274068 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_telPathway - Telomeres, Telomerase, Cellular Aging, and Immortality
Reactome (by CSHL, EBI, and GO)
Protein P12956 (Reactome details) participates in the following event(s):
R-HSA-175174 Association of Ku heterodimer with viral DNA ends R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-175258 2-LTR formation due to circularization of viral DNA R-HSA-5693604 XRCC4:LIG4 ligates DNA DSB ends during NHEJ R-HSA-3134821 DNA-PK binds microbial dsDNA R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-6798748 Exocytosis of secretory granule lumen proteins R-HSA-5693615 Association of DNA-PKcs with Ku-bound ends of DNA double-strand breaks - synapsis R-HSA-175177 Association of XRCC4:DNA ligase IV complex with viral DNA ends R-HSA-5693575 DNA-PKcs autophosphorylates R-HSA-5686924 DCLRE1C binds PRKDC:XRCC5:XRCC6 at DNA DSBs R-HSA-5693574 XRCC4:LIG4, NHEJ1 and POLL or POLM bind DNA DSBs in NHEJ R-HSA-5693578 TDP1 and TDP2 process unligatable DSB ends R-HSA-5687360 POLL or POLM extends aligned DNA DSB ends to fill gaps R-HSA-5693533 DCLRE1C (ARTEMIS) processes DNA DSB ends R-HSA-5687183 PRKDC phosphorylates DCLRE1C at DNA DSBs R-HSA-164843 2-LTR circle formation R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-6798695 Neutrophil degranulation R-HSA-162592 Integration of provirus R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-168249 Innate Immune System R-HSA-162594 Early Phase of HIV Life Cycle R-HSA-73894 DNA Repair R-HSA-168256 Immune System R-HSA-162587 HIV Life Cycle R-HSA-162906 HIV Infection R-HSA-5663205 Infectious disease R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
