Description: Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) (XRCC5), mRNA. RefSeq Summary (NM_021141): The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr2:216,974,020-217,071,016 Size: 96,997 Total Exon Count: 21 Strand: + Coding Region Position: hg19 chr2:216,974,160-217,069,925 Size: 95,766 Coding Exon Count: 21
ID:XRCC5_HUMAN DESCRIPTION: RecName: Full=X-ray repair cross-complementing protein 5; EC=3.6.4.-; AltName: Full=86 kDa subunit of Ku antigen; AltName: Full=ATP-dependent DNA helicase 2 subunit 2; AltName: Full=ATP-dependent DNA helicase II 80 kDa subunit; AltName: Full=CTC box-binding factor 85 kDa subunit; Short=CTC85; Short=CTCBF; AltName: Full=DNA repair protein XRCC5; AltName: Full=Ku80; AltName: Full=Ku86; AltName: Full=Lupus Ku autoantigen protein p86; AltName: Full=Nuclear factor IV; AltName: Full=Thyroid-lupus autoantigen; Short=TLAA; AltName: Full=X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining); 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. 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. SUBUNIT: Heterodimer of a 70 kDa and a 80 kDa 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 displays DNA binding activity towards the osteocalcin FGF response element (OCFRE). In addition, the 80 kDa subunit binds to the osteoblast-specific transcription factors MSX2 and RUNX2. Interacts with ELF3. May interact with APLF. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1. INTERACTION: P09629:HOXB7; NbExp=9; IntAct=EBI-357997, EBI-1248457; P78527:PRKDC; NbExp=6; IntAct=EBI-357997, EBI-352053; P12956:XRCC6; NbExp=8; IntAct=EBI-357997, EBI-353208; SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Chromosome. DEVELOPMENTAL STAGE: Expression increases during promyelocyte differentiation. INDUCTION: In osteoblasts, by FGF2. DOMAIN: The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage. PTM: Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity. PTM: Sumoylated. PTM: Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination following DNA damage, leading to its degradation and removal from DNA damage sites. MISCELLANEOUS: Individuals with systemic lupus erythematosus (SLE) and related disorders produce extremely large amounts of autoantibodies to XRCC6 and XRCC5. SIMILARITY: Belongs to the ku80 family. SIMILARITY: Contains 1 Ku domain. WEB RESOURCE: Name=NIEHS SNPs; URL="http://egp.gs.washington.edu/data/xrcc5/";
cancer Price EA et al. 1997, Rare microsatellite polymorphisms in the DNA repair genes XRCC1 XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity., Somatic cell and molecular genetics. 1997 Jul;23(4):237-47.
[PubMed 9542526]
cancer Price EA et al. 1997, Rare microsatellite polymorphisms in the DNA repair genes XRCC1 XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity., Somatic cell and molecular genetics. 1997 Jul;23(4):237-47.
[PubMed 9542526]
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 P13010
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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:0006281 DNA repair GO:0006302 double-strand break 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:0008283 cell proliferation GO:0032204 regulation of telomere maintenance GO:0032212 positive regulation of telomere maintenance via telomerase GO:0032481 positive regulation of type I interferon production GO:0032508 DNA duplex unwinding GO:0042493 response to drug GO:0043085 positive regulation of catalytic activity 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:0048660 regulation of smooth muscle cell proliferation GO:0050769 positive regulation of neurogenesis GO:0051973 positive regulation of telomerase activity GO:0060218 hematopoietic stem cell differentiation GO:0070198 protein localization to chromosome, telomeric region GO:0071398 cellular response to fatty acid 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:1904430 negative regulation of t-circle formation GO:1990830 cellular response to leukemia inhibitory factor
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