XRCC5 [The Human Chemical-Genetic Interaction Map Project]

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======= XRCC5 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: XRCC5
  * **<color #00a2e8>Official Name</color>**: X-ray repair cross complementing 5
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7520|7520]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P13010|P13010]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=XRCC5&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20XRCC5|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/194364|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). Plays a role in the regulation of DNA virus- mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. {ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Ku|
|Ku N|
|Ku C|
|Ku PK bind|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|DNA end binding|
|Ku70:Ku80 complex|
|cellular hyperosmotic salinity response|
|5-deoxyribose-5-phosphate lyase activity|
|negative regulation of t-circle formation|
|establishment of integrated proviral latency|
|cellular response to salt stress|
|regulation of t-circle formation|
|nonhomologous end joining complex|
|establishment of viral latency|
|double-stranded telomeric DNA binding|
|hyperosmotic salinity response|
|nuclear telomere cap complex|
|cellular response to X-ray|
|cellular hyperosmotic response|
|viral latency|
|hematopoietic stem cell differentiation|
|protein localization to chromosome, telomeric region|
|site of DNA damage|
|response to salt stress|
|hyperosmotic response|
|telomeric DNA binding|
|response to X-ray|
|cellular response to gamma radiation|
|positive regulation of telomere maintenance via telomerase|
|cellular response to osmotic stress|
|positive regulation of telomerase activity|
|negative regulation of telomere maintenance|
|positive regulation of telomere maintenance via telomere lengthening|
|protein-DNA complex|
|enzyme activator activity|
|positive regulation of telomere maintenance|
|regulation of telomerase activity|
|regulation of telomere maintenance via telomerase|
|cellular response to fatty acid|
|damaged DNA binding|
|response to gamma radiation|
|double-strand break repair via nonhomologous end joining|
|DNA helicase activity|
|regulation of telomere maintenance via telomere lengthening|
|protein localization to chromosome|
|non-recombinational repair|
|positive regulation of DNA biosynthetic process|
|cellular response to ionizing radiation|
|response to osmotic stress|
|positive regulation of type I interferon production|
|regulation of telomere maintenance|
|response to fatty acid|
|hematopoietic progenitor cell differentiation|
|cellular response to leukemia inhibitory factor|
|response to leukemia inhibitory factor|
|telomere maintenance|
|telomere organization|
|double-stranded DNA binding|
|nuclear chromosome, telomeric region|
|DNA duplex unwinding|
|regulation of DNA biosynthetic process|
|secretory granule lumen|
|DNA geometric change|
|negative regulation of DNA metabolic process|
|regulation of type I interferon production|
|regulation of smooth muscle cell proliferation|
|negative regulation of chromosome organization|
|response to ionizing radiation|
|ribonucleoprotein complex|
|stem cell differentiation|
|positive regulation of chromosome organization|
|cellular response to radiation|
|double-strand break repair|
|protein C-terminus binding|
|positive regulation of DNA metabolic process|
|cellular response to acid chemical|
|transcription regulatory region DNA binding|
|DNA recombination|
|activation of innate immune response|
|protein-containing complex binding|
|ubiquitin protein ligase binding|
|DNA conformation change|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|positive regulation of innate immune response|
|anatomical structure homeostasis|
|response to acid chemical|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|positive regulation of response to biotic stimulus|
|negative regulation of organelle organization|
|response to radiation|
|positive regulation of cytokine production|
|regulation of innate immune response|
|positive regulation of neurogenesis|
|positive regulation of defense response|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|positive regulation of multi-organism process|
|DNA repair|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|myeloid cell activation involved in immune response|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cell development|
|cell population proliferation|
|hemopoiesis|
|positive regulation of kinase activity|
|myeloid leukocyte activation|
|protein-containing complex|
|positive regulation of response to external stimulus|
|hematopoietic or lymphoid organ development|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|immune system development|
|positive regulation of transferase activity|
|regulation of cytokine production|
|viral process|
|regulated exocytosis|
|negative regulation of cellular component organization|
|protein localization to organelle|
|brain development|
|DNA metabolic process|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|head development|
|symbiotic process|
|exocytosis|
|regulation of protein kinase activity|
|regulation of neurogenesis|
|interspecies interaction between organisms|
|response to lipid|
|nucleolus|
|positive regulation of immune response|
|regulation of kinase activity|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|defense response to other organism|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|regulation of transferase activity|
|central nervous system development|
|secretion by cell|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|response to drug|
|export from cell|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|chromosome organization|
|cell activation|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|homeostatic process|
|regulation of immune system process|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|regulation of protein modification process|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|membrane|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp264|Arsenate 40μM R06 exp264]]|-2.77|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|-2.09|
|[[:results:exp68|Clomiphene 4.4μM R02 exp68]]|-2.08|
|[[:results:exp301|VER-155008 3.9μM R06 exp301]]|-2.01|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-1.89|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|-1.88|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|-1.85|
|[[:results:exp275|Citral 75μM R06 exp275]]|-1.8|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|-1.71|
|[[:results:exp141|Nifurtimox 1μM R03 exp141]]|1.73|
|[[:results:exp4|Actinomycin-D 0.01μM R00 exp4]]|1.84|
|[[:results:exp321|ABT-702 5μM plus Deferoxamine 11μM R07 exp321]]|1.87|
|[[:results:exp151|SGC0946 7μM R03 exp151]]|1.91|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 154/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|4/28|
|blood|6/28|
|bone|11/26|
|breast|7/33|
|central nervous system|15/56|
|cervix|2/4|
|colorectal|4/17|
|esophagus|3/13|
|fibroblast|1/1|
|gastric|3/16|
|kidney|3/21|
|liver|3/20|
|lung|12/75|
|lymphocyte|2/16|
|ovary|3/26|
|pancreas|2/24|
|peripheral nervous system|10/16|
|plasma cell|1/15|
|prostate|0/1|
|skin|12/24|
|soft tissue|1/9|
|thyroid|1/2|
|upper aerodigestive|1/22|
|urinary tract|5/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 938
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.14 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='XRCC5 Expression in NALM6 Cells: 9.14'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>