X-ray repair cross-complementing protein 5 (XRCC5)
The protein contains 732 amino acids for an estimated molecular weight of 82705 Da.
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 (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). 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 (PubMed:20383123). 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 (PubMed:8621488). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs1805380 | |
| dbSNP:rs2287558 |
Biological Process
Activation of innate immune response
Brain development
Cell population proliferation
Cellular hyperosmotic salinity response
Cellular response to DNA damage stimulus
Cellular response to fatty acid
Cellular response to gamma radiation
Cellular response to leukemia inhibitory factor
Cellular response to X-ray
DNA duplex unwinding
DNA recombination
DNA repair
Double-strand break repair
Double-strand break repair via nonhomologous end joining
Establishment of integrated proviral latency
Hematopoietic stem cell differentiation
Innate immune response
Negative regulation of t-circle formation
Negative regulation of transcription, DNA-templated
Neutrophil degranulation
Positive regulation of catalytic activity
Positive regulation of neurogenesis
Positive regulation of protein kinase activity
Positive regulation of telomerase activity
Positive regulation of telomere maintenance via telomerase
Positive regulation of type I interferon production
Protein localization to chromosome, telomeric region
Regulation of smooth muscle cell proliferation
Regulation of telomere maintenance
Response to drug
Small-subunit processome assembly
Telomere maintenance
Transcription, DNA-templated
Viral process
Cellular Component
Chromosome, telomeric region
Cytosol
Extracellular region
Intracellular ribonucleoprotein complex
Ku70:Ku80 complex
Membrane
Nonhomologous end joining complex
Nuclear chromosome, telomeric region
Nuclear telomere cap complex
Nucleolus
Nucleoplasm
Nucleus
Plasma membrane
Protein complex
Protein-containing complex
Protein-DNA complex
Ribonucleoprotein complex
Secretory granule lumen
Site of DNA damage
Small-subunit processome
Molecular Function
ATP binding
ATP-dependent DNA helicase activity
ATPase, acting on DNA
Damaged DNA binding
DNA binding
DNA end binding
DNA helicase activity
Double-stranded DNA binding
Enzyme activator activity
Poly(A) RNA binding
Protein C-terminus binding
Protein-containing complex binding
RNA binding
Telomeric DNA binding
Transcription cis-regulatory region binding
Transcription regulatory region DNA binding
U3 snoRNA binding
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 194364
X-ray repair, complementing defective, in chinese hamster, 5; xrcc5
Ku antigen, 80-kd subunit; ku80
Ku86
DESCRIPTION
The human XRCC5 DNA repair gene complements the radiosensitive mutant xrs-6, derived from Chinese hamster ovary cells which are defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. The XRCC5 gene encodes the 80-kD subunit of the Ku autoantigen, a heterodimer which contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the nonhomologous end joining (NHEJ) pathway.CLONING
A DNA double-strand break is a major lesion that destroys the integrity of the DNA molecule. Such damage is introduced by ionizing radiation. A number of mutants defective in the repair of DNA double-strand breaks have been identified in rodent cells and classified into distinct complementation groups. The repair gene defective in one group of mutants was designated XRCC5. Using the method of microcell-mediated chromosome transfer, Jeggo et al. (1992) achieved complementation of the repair defect in hamster xrs mutants by transfer of human chromosome 2. The sensitivity of these cells to ionizing radiation and their impaired ability to rejoin radiation-induced DNA double-strand breaks were corrected by chromosome 2, although the correction of radiation sensitivity was only partial. Complementation was observed in 1 hybrid which contained only the long arm of chromosome 2. Taccioli et al. (1994) showed through genetic and biochemical approaches that the XRCC5 is the 80-kilodalton subunit of the Ku protein. Ku binds to free double-stranded DNA ends and is the DNA-binding component of the DNA-dependent protein kinase. Thus, the Ku protein is involved in DNA repair and in V(D)J recombination, and the Ku-DNA-dependent protein kinase complex may have a role in those same processes. See 152690 for discussion of the Ku p70 subunit.GENE FUNCTION
Tuteja et al. (1994) purified from HeLa cells an enzyme they called DNA helicase II, an ATP-dependent DNA unwinding enzyme. They showed that it is a heterodimer of 72 and 87 kD polypeptides. Sequencing showed that it is identical to the Ku autoantigen. The exclusively nuclear location of this particular DNA helicase II/Ku antigen, its highly specific affinity for double-stranded DNA, its abundance, and its exclusive DNA-duplex unwinding activity pointed to additional roles for this molecule in DNA metabolism. Li et al. (2002) constructed a human somatic cell line containing a targeted disruption of the Ku86 locus. Human colon cancer cells heterozygous for Ku86 were haploinsufficient with an increase in polyploid cells, a reduction in cell proliferation, elevated p53 levels, and a slight hypersensitivity to ionizing radiation. Functional inactivation of the second Ku86 allele resulted in cells with a drastically reduced doubling time. These cells were capable of undergoing only a limited number of cell divisions, after which they underwent apoptosis. These experiments demonstrated that the Ku86 locus is essential in human somatic tissue culture cells. Using human and hamster cells, Mari et al. (2006) showed that Ku heterodimers on DNA ends were in dynamic equilibrium with Ku70/Ku80 in solution, suggesting that formation of the NHEJ complex is reversible. Accumulation of XRCC4 (194363) on DNA double-strand breaks depended on the presence of Ku70/Ku80, but not PRKDC (600899). Mari et al. (2006) found that XRCC4 interacted directly with Ku70, and they hypothesized that XRCC4 serves as a flexible tether be ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 194364 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed