| CEP95 (17q23.3) / XRCC5 (2q35) | GIGYF2 (2q37.1) / XRCC5 (2q35) | GSTP1 (11q13.2) / XRCC5 (2q35) |
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SERPINE2 (2q36.1) / XRCC5 (2q35) | WDR7 (18q21.31) / XRCC5 (2q35) | XRCC5 (2q35) / ACADL (2q34) |
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XRCC5 (2q35) / HTR2B (2q37.1) | XRCC5 (2q35) / MYO5A (15q21.2) | XRCC5 (2q35) / PTGR1 (9q31.3) |
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Description | Two isoforms of Ku80 encoded by the same genes, namely Ku80 and Karp-1 are expressed and function in primate cells. Karp-1 has some biochemical properties, which resemble those of Ku80, and the function of Karp-1 could partially replace that of Ku80 in DSB repair (Koibe et al., 2011). However the role in the cells of this isoform is still unclear. The Ku80 protein is 732 amino acid long and its molecular weight is 83 kDa. It is composed of 3 domains: an amino (N) terminal alpha/beta domain, a central beta-barrel domain and a helical-C terminal arm. The 19 kDa C-terminal region of Ku80 is implicated in the recruitment of DNA-PKcs by Ku to sites of damage (Rivera-Calzada et al., 2007). Moreover it belongs to the "Care Taker gene", detecting double strands breaks. |
Expression | Ku80 expression has been demonstrated in various cell types and its localization changes during the cell-cycle progression or with a pathological state. Ku80 in addition to its well known regulatory functions in DNA repair, revealed to behave as a somatostatin receptor in gastric carcinoma cell (Le Romancer, 1994). |
Localisation | Ku was originally reported to be a nuclear protein, consistent with its function as a subunits of DNA- PK involved in DNA double strand breaks repair. However several studies have revealed the cytoplasmic or cell surface localization of ku proteins in various cell types (Prabhakar et al., 1990). In highly infiltrative and metastatic tumors of the colon, breast and bladder, the impaired DNA-repair activity is due to the loss of Ku80 and to the Ku70 shifting from the nucleus to the cytoplasm (Pucci et al., 2001). This mechanism can be controlled by various external growth-regulating stimuli. In normal cell Ku80 activation and translocation into nucleus could be regulated or stimulated by the induction of nuclear Clusterin (nClu)-Ku70 interactions. (Pucci et al., 2009a; Pucci et al., 2009b; Mazzarelli et al., 2009). |
Function | Ku80 is one component of a protein complex, the Ku70/80 heterodimer that can bind tightly to free DNA ends and activate the DNA-PKcs. The principal role of Ku proteins is to take care of the homeostasis of the genome being involved in telomere maintenance, regulation of apoptosis induction, specific gene transcription, DNA replication and cell-cycle regulation. The function of this caretaker gene is to suppress chromosomal aberrations translocation and aneuploidy. It has been demonstrated that Ku80 may act as a caretaker gene that maintains the integrity of the genoma by a mechanism involving the suppression of chromosomal rearrangements (Difilippantonio et al., 2000). |
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| A. Ku80 is localized in the nucleus in normal, undamaged cell interacting with the Ku70 protein. sCLU stabilizes the Ku70-Bax interaction in the cytoplasm acting as cytoprotectant. B. After DNA damage inducing DNA double-strand breaks repair (UV treatment, ionizing radiation, etc.) Ku70 allows the translocation of Bax to the mitochondria inducing apoptosis (Mazzarelli et al., 2009). C. The differential shift of clusterin isoform production, the loss of Ku80, and the cytoplasmic relocalization of Ku70 are related to cell death inhibition and cancer progression. |
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Note | |
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Entity | Cancer insurgence and progression |
Note | The changes in Ku70 and Ku80 expression and localization are related to tumor progression. In normal cell they usually are placed in the nucleus, where they cooperate to repair double strands breaks that could occur during DNA replication. In breast, bladder, and colon cancers (Pucci et al., 2004a; Pucci et al., 2009c) DNA repair is inhibited in high infiltrative carcinomas through the loss of Ku80 and the Ku70 cell compartment shifting from nucleus to the cytoplasm. Ku70 shifts from the nucleus to the cytoplasm and binds, together with sCLU, Bax inhibiting its homodimerization and translocation to the mitochondria preventing apoptosis induction. Somatostatin treatment to a colon carcinoma cell line (Caco-2) strongly modulates the activation of Ku70/80 heterodimer and the level of Ku80 in the nucleus by increasing its specific mRNA level (Pucci et al., 2004b). Ku80 could be a signal transducer and activator factor behaving as the intermediate of the SST transduction pathway by the internalization and the migration from the cell membrane to the nucleus. |
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| Tumor-specific modulation of Ku70/80 in human colon cancer. Ku70 staining was strongly positive in the nuclei of normal mucosa. In node-negative carcinomas (pT3N0) Ku70 expression slightly decreased and it localized mainly in the nucleus. In node-positive carcinomas (pT3N1) Ku70 staining was distributed mainly in cytoplasm. The expression of Ku80 was positive in the nuclei of control tissues (normal mucosa). Nuclear Ku80 expression was strongly decreased in node-negative tumors (pT3N0). No staining for Ku80 was found in the nucleus or in the cytoplasm of node-positive carcinomas (pT3N1). |
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DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. |
Difilippantonio MJ, Zhu J, Chen HT, Meffre E, Nussenzweig MC, Max EE, Ried T, Nussenzweig A. |
Nature. 2000 Mar 30;404(6777):510-4. |
PMID 10761921 |
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KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair. |
Koike M, Yutoku Y, Koike A. |
Exp Cell Res. 2011 Oct 1;317(16):2267-75. Epub 2011 Jul 2. |
PMID 21756904 |
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The 86-kDa subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity. |
Le Romancer M, Reyl-Desmars F, Cherifi Y, Pigeon C, Bottari S, Meyer O, Lewin MJ. |
J Biol Chem. 1994 Jul 1;269(26):17464-8. |
PMID 8021251 |
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CLU and colon cancer. The dual face of CLU: from normal to malignant phenotype. |
Mazzarelli P, Pucci S, Spagnoli LG. |
Adv Cancer Res. 2009;105:45-61. (REVIEW) |
PMID 19879422 |
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Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. |
Prabhakar BS, Allaway GP, Srinivasappa J, Notkins AL. |
J Clin Invest. 1990 Oct;86(4):1301-5. |
PMID 2212014 |
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Clusterin in stool: a new biomarker for colon cancer screening? |
Pucci S, Bonanno E, Sesti F, Mazzarelli P, Mauriello A, Ricci F, Zoccai GB, Rulli F, Galata G, Spagnoli LG. |
Am J Gastroenterol. 2009a Nov;104(11):2807-15. Epub 2009 Jul 21. |
PMID 19623170 |
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CLU "in and out": looking for a link. |
Pucci S, Mazzarelli P, Nucci C, Ricci F, Spagnoli LG. |
Adv Cancer Res. 2009c;105:93-113. (REVIEW) |
PMID 19879425 |
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Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. |
Rivera-Calzada A, Spagnolo L, Pearl LH, Llorca O. |
EMBO Rep. 2007 Jan;8(1):56-62. Epub 2006 Dec 8. |
PMID 17159921 |
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| Nomenclature |
HGNC (Hugo) | XRCC5 12833 |
| Cards |
Atlas | XRCC5ID337ch2q35 |
Entrez_Gene (NCBI) | XRCC5 7520 X-ray repair cross complementing 5 |
Aliases | KARP-1; KARP1; KU80; KUB2; |
| Ku86; NFIV |
GeneCards (Weizmann) | XRCC5 |
Ensembl hg19 (Hinxton) | ENSG00000079246 [Gene_View] |
Ensembl hg38 (Hinxton) | ENSG00000079246 [Gene_View] chr2:216109297-216206293 [Contig_View] XRCC5 [Vega] |
ICGC DataPortal | ENSG00000079246 |
TCGA cBioPortal | XRCC5 |
AceView (NCBI) | XRCC5 |
Genatlas (Paris) | XRCC5 |
WikiGenes | 7520 |
SOURCE (Princeton) | XRCC5 |
Genetics Home Reference (NIH) | XRCC5 |
| Genomic and cartography |
GoldenPath hg38 (UCSC) | XRCC5 - chr2:216109297-216206293 + 2q35 [Description] (hg38-Dec_2013) |
GoldenPath hg19 (UCSC) | XRCC5 - 2q35 [Description] (hg19-Feb_2009) |
Ensembl | XRCC5 - 2q35 [CytoView hg19] XRCC5 - 2q35 [CytoView hg38] |
Mapping of homologs : NCBI | XRCC5 [Mapview hg19] XRCC5 [Mapview hg38] |
OMIM | 194364 |
| Gene and transcription |
Genbank (Entrez) | AK026166 AK096408 AK222603 AK290740 BC019027 |
RefSeq transcript (Entrez) | NM_021141 |
RefSeq genomic (Entrez) | |
Consensus coding sequences : CCDS (NCBI) | XRCC5 |
Cluster EST : Unigene | Hs.388739 [ NCBI ] |
CGAP (NCI) | Hs.388739 |
Alternative Splicing Gallery | ENSG00000079246 |
Gene Expression | XRCC5 [ NCBI-GEO ] XRCC5 [ EBI - ARRAY_EXPRESS ]
XRCC5 [ SEEK ] XRCC5 [ MEM ] |
Gene Expression Viewer (FireBrowse) | XRCC5 [ Firebrowse - Broad ] |
SOURCE (Princeton) | Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60] |
Genevestigator | Expression in : [tissues]  [cell-lines]  [cancer]  [perturbations]   |
BioGPS (Tissue expression) | 7520 |
GTEX Portal (Tissue expression) | XRCC5 |
Human Protein Atlas | ENSG00000079246-XRCC5 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
UniProt/SwissProt | P13010 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
NextProt | P13010 [Sequence] [Exons] [Medical] [Publications] |
With graphics : InterPro | P13010 |
Splice isoforms : SwissVar | P13010 |
Catalytic activity : Enzyme | 3.6.4.- [ Enzyme-Expasy ] 3.6.4.-3.6.4.- [ IntEnz-EBI ] 3.6.4.- [ BRENDA ] 3.6.4.- [ KEGG ] |
PhosPhoSitePlus | P13010 |
Domains : Interpro (EBI) | Ku70/Ku80_beta-barrel_dom Ku80 Ku_C Ku_N Ku_PK_bind SPOC-like_C_dom VWF_A |
Domain families : Pfam (Sanger) | Ku (PF02735) Ku_C (PF03730) Ku_N (PF03731) Ku_PK_bind (PF08785) |
Domain families : Pfam (NCBI) | pfam02735 pfam03730 pfam03731 pfam08785 |
Domain families : Smart (EMBL) | Ku78 (SM00559) VWA (SM00327) |
Conserved Domain (NCBI) | XRCC5 |
DMDM Disease mutations | 7520 |
Blocks (Seattle) | XRCC5 |
PDB (SRS) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
PDB (PDBSum) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
PDB (IMB) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
PDB (RSDB) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
Structural Biology KnowledgeBase | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
SCOP (Structural Classification of Proteins) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
CATH (Classification of proteins structures) | 1JEQ 1JEY 1Q2Z 1RW2 3RZ9 |
Superfamily | P13010 |
Human Protein Atlas [tissue] | ENSG00000079246-XRCC5 [tissue] |
Peptide Atlas | P13010 |
HPRD | 08935 |
IPI | IPI00220834 IPI00012911 IPI00871391 IPI00926445 |
| Protein Interaction databases |
DIP (DOE-UCLA) | P13010 |
IntAct (EBI) | P13010 |
FunCoup | ENSG00000079246 |
BioGRID | XRCC5 |
STRING (EMBL) | XRCC5 |
ZODIAC | XRCC5 |
| Ontologies - Pathways |
QuickGO | P13010 |
Ontology : AmiGO | telomere maintenance nuclear telomere cap complex nuclear chromosome, telomeric region nuclear chromosome, telomeric region activation of innate immune response DNA binding damaged DNA binding double-stranded DNA binding double-stranded telomeric DNA binding RNA binding RNA binding ATP-dependent DNA helicase activity protein binding ATP binding extracellular region nucleus nucleoplasm nucleoplasm nucleolus cytosol plasma membrane double-strand break repair double-strand break repair via nonhomologous end joining double-strand break repair via nonhomologous end joining double-strand break repair via nonhomologous end joining DNA recombination transcription, DNA-templated brain development protein C-terminus binding enzyme activator activity cell proliferation membrane intracellular ribonucleoprotein complex ubiquitin protein ligase binding regulation of telomere maintenance positive regulation of telomere maintenance via telomerase positive regulation of type I interferon production DNA duplex unwinding protein-DNA complex secretory granule lumen telomeric DNA binding telomeric DNA binding response to drug positive regulation of catalytic activity protein complex neutrophil degranulation Ku70:Ku80 complex Ku70:Ku80 complex transcription regulatory region DNA binding innate immune response positive regulation of protein kinase activity negative regulation of transcription, DNA-templated regulation of smooth muscle cell proliferation positive regulation of neurogenesis 5'-deoxyribose-5-phosphate lyase activity positive regulation of telomerase activity hematopoietic stem cell differentiation protein localization to chromosome, telomeric region nonhomologous end joining complex cellular response to fatty acid cellular hyperosmotic salinity response cellular response to gamma radiation cellular response to X-ray establishment of integrated proviral latency negative regulation of t-circle formation cellular response to leukemia inhibitory factor |
Ontology : EGO-EBI | telomere maintenance nuclear telomere cap complex nuclear chromosome, telomeric region nuclear chromosome, telomeric region activation of innate immune response DNA binding damaged DNA binding double-stranded DNA binding double-stranded telomeric DNA binding RNA binding RNA binding ATP-dependent DNA helicase activity protein binding ATP binding extracellular region nucleus nucleoplasm nucleoplasm nucleolus cytosol plasma membrane double-strand break repair double-strand break repair via nonhomologous end joining double-strand break repair via nonhomologous end joining double-strand break repair via nonhomologous end joining DNA recombination transcription, DNA-templated brain development protein C-terminus binding enzyme activator activity cell proliferation membrane intracellular ribonucleoprotein complex ubiquitin protein ligase binding regulation of telomere maintenance positive regulation of telomere maintenance via telomerase positive regulation of type I interferon production DNA duplex unwinding protein-DNA complex secretory granule lumen telomeric DNA binding telomeric DNA binding response to drug positive regulation of catalytic activity protein complex neutrophil degranulation Ku70:Ku80 complex Ku70:Ku80 complex transcription regulatory region DNA binding innate immune response positive regulation of protein kinase activity negative regulation of transcription, DNA-templated regulation of smooth muscle cell proliferation positive regulation of neurogenesis 5'-deoxyribose-5-phosphate lyase activity positive regulation of telomerase activity hematopoietic stem cell differentiation protein localization to chromosome, telomeric region nonhomologous end joining complex cellular response to fatty acid cellular hyperosmotic salinity response cellular response to gamma radiation cellular response to X-ray establishment of integrated proviral latency negative regulation of t-circle formation cellular response to leukemia inhibitory factor |
Pathways : BIOCARTA | Telomeres, Telomerase, Cellular Aging, and Immortality [Genes] |
REACTOME | P13010 [protein] |
REACTOME Pathways | R-HSA-6798695 [pathway] |
NDEx Network | XRCC5 |
Atlas of Cancer Signalling Network | XRCC5 |
Wikipedia pathways | XRCC5 |
| Orthology - Evolution |
OrthoDB | 7520 |
GeneTree (enSembl) | ENSG00000079246 |
Phylogenetic Trees/Animal Genes : TreeFam | XRCC5 |
HOVERGEN | P13010 |
HOGENOM | P13010 |
Homologs : HomoloGene | XRCC5 |
Homology/Alignments : Family Browser (UCSC) | XRCC5 |
| Gene fusions - Rearrangements |
Fusion: TCGA_MDACC | XRCC5 2q35 ACADL 2q34 PRAD |
Fusion Portal | XRCC5 2q35 ACADL 2q34 PRAD |
Fusion : Quiver | XRCC5 |
| Polymorphisms : SNP and Copy number variants |
NCBI Variation Viewer | XRCC5 [hg38] |
dbSNP Single Nucleotide Polymorphism (NCBI) | XRCC5 |
dbVar | XRCC5 |
ClinVar | XRCC5 |
1000_Genomes | XRCC5 |
Exome Variant Server | XRCC5 |
ExAC (Exome Aggregation Consortium) | ENSG00000079246 |
GNOMAD Browser | ENSG00000079246 |
Genetic variants : HAPMAP | 7520 |
Genomic Variants (DGV) | XRCC5 [DGVbeta] |
DECIPHER | XRCC5 [patients] [syndromes] [variants] [genes] |
CONAN: Copy Number Analysis | XRCC5 |
| Mutations |
ICGC Data Portal | XRCC5 |
TCGA Data Portal | XRCC5 |
Broad Tumor Portal | XRCC5 |
OASIS Portal | XRCC5 [ Somatic mutations - Copy number] |
Somatic Mutations in Cancer : COSMIC | XRCC5 [overview] [genome browser] [tissue] [distribution] |
Mutations and Diseases : HGMD | XRCC5 |
LOVD (Leiden Open Variation Database) | Whole genome datasets |
LOVD (Leiden Open Variation Database) | LOVD - Leiden Open Variation Database |
LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
BioMuta | search XRCC5 |
DgiDB (Drug Gene Interaction Database) | XRCC5 |
DoCM (Curated mutations) | XRCC5 (select the gene name) |
CIViC (Clinical Interpretations of Variants in Cancer) | XRCC5 (select a term) |
intoGen | XRCC5 |
NCG5 (London) | XRCC5 |
Cancer3D | XRCC5(select the gene name) |
Impact of mutations | [PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
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OMIM | 194364 |
Orphanet | |
DisGeNET | XRCC5 |
Medgen | XRCC5 |
Genetic Testing Registry | XRCC5
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NextProt | P13010 [Medical] |
TSGene | 7520 |
GENETests | XRCC5 |
Target Validation | XRCC5 |
Huge Navigator |
XRCC5 [HugePedia] |
snp3D : Map Gene to Disease | 7520 |
BioCentury BCIQ | XRCC5 |
ClinGen | XRCC5 |
| Clinical trials, drugs, therapy |
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Chemical/Protein Interactions : CTD | 7520 |
Chemical/Pharm GKB Gene | PA37425 |
Clinical trial | XRCC5 |
| Miscellaneous |
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canSAR (ICR) | XRCC5 (select the gene name) |
| Probes |
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| Litterature |
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PubMed | 393 Pubmed reference(s) in Entrez |
GeneRIFs | Gene References Into Functions (Entrez) |
CoreMine | XRCC5 |
EVEX | XRCC5 |
GoPubMed | XRCC5 |
iHOP | XRCC5 |