BRCA2 [The Human Chemical-Genetic Interaction Map Project]

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======= BRCA2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: BRCA2
  * **<color #00a2e8>Official Name</color>**: BRCA2 DNA repair associated
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=675|675]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P51587|P51587]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=BRCA2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20BRCA2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600185|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, Dec 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop- associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}.

<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'>
|Tower|
|BRCA2|
|BRCA-2 OB1|
|BRCA-2 OB3|
|BRCA-2 helical|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|BRCA2-MAGE-D1 complex|
|cell cycle DNA replication maintenance of fidelity|
|mitotic DNA replication maintenance of fidelity|
|mitotic recombination-dependent replication fork processing|
|H3 histone acetyltransferase activity|
|negative regulation of mammary gland epithelial cell proliferation|
|establishment of protein localization to telomere|
|replication fork protection|
|H4 histone acetyltransferase activity|
|mitotic DNA replication|
|telomere maintenance via recombination|
|lateral element|
|inner cell mass cell proliferation|
|DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator|
|establishment of protein localization to chromosome|
|DNA damage response, signal transduction resulting in transcription|
|protein localization to chromosome, telomeric region|
|response to UV-C|
|regulation of mammary gland epithelial cell proliferation|
|mitotic recombination|
|blastocyst growth|
|oocyte maturation|
|male meiosis I|
|negative regulation of DNA-dependent DNA replication|
|gamma-tubulin binding|
|response to X-ray|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|centrosome duplication|
|replication fork processing|
|oocyte development|
|DNA-dependent DNA replication maintenance of fidelity|
|negative regulation of DNA replication|
|oocyte differentiation|
|nuclear DNA replication|
|cell cycle DNA replication|
|histone H3 acetylation|
|male meiotic nuclear division|
|histone acetyltransferase activity|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|regulation of DNA-dependent DNA replication|
|histone H4 acetylation|
|response to gamma radiation|
|protein localization to chromosome|
|cell aging|
|mitotic cytokinesis|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|oogenesis|
|DNA damage response, signal transduction by p53 class mediator|
|centrosome cycle|
|secretory granule|
|female gonad development|
|regulation of cytokinesis|
|microtubule organizing center organization|
|development of primary female sexual characteristics|
|cytoskeleton-dependent cytokinesis|
|double-strand break repair via homologous recombination|
|blastocyst development|
|recombinational repair|
|cytokinesis|
|telomere maintenance|
|telomere organization|
|protease binding|
|signal transduction in response to DNA damage|
|female sex differentiation|
|single-stranded DNA binding|
|regulation of DNA replication|
|nuclear chromosome, telomeric region|
|meiosis I|
|nucleotide-excision repair|
|meiosis I cell cycle process|
|histone acetylation|
|internal peptidyl-lysine acetylation|
|signal transduction by p53 class mediator|
|DNA-dependent DNA replication|
|peptidyl-lysine acetylation|
|internal protein amino acid acetylation|
|negative regulation of epithelial cell proliferation|
|female gamete generation|
|anatomical structure maturation|
|response to UV|
|protein acetylation|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|positive regulation of mitotic cell cycle|
|meiotic nuclear division|
|cell maturation|
|meiotic cell cycle process|
|regulation of cell division|
|double-strand break repair|
|protein acylation|
|protein C-terminus binding|
|gonad development|
|DNA replication|
|development of primary sexual characteristics|
|DNA recombination|
|meiotic cell cycle|
|developmental maturation|
|germ cell development|
|sex differentiation|
|aging|
|apoptotic signaling pathway|
|nuclear division|
|response to light stimulus|
|organelle fission|
|peptidyl-lysine modification|
|regulation of epithelial cell proliferation|
|anatomical structure homeostasis|
|cellular process involved in reproduction in multicellular organism|
|histone modification|
|covalent chromatin modification|
|in utero embryonic development|
|positive regulation of cell cycle|
|developmental growth|
|growth|
|reproductive structure development|
|reproductive system development|
|establishment of protein localization to organelle|
|response to radiation|
|microtubule cytoskeleton organization|
|centrosome|
|cell division|
|DNA repair|
|spermatogenesis|
|cell population proliferation|
|hemopoiesis|
|male gamete generation|
|protein-containing complex|
|mitotic cell cycle process|
|hematopoietic or lymphoid organ development|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|developmental process involved in reproduction|
|microtubule-based process|
|negative regulation of cell population proliferation|
|mitotic cell cycle|
|gamete generation|
|chromatin organization|
|protein localization to organelle|
|brain development|
|DNA metabolic process|
|regulation of cell cycle process|
|cellular response to DNA damage stimulus|
|head development|
|multicellular organismal reproductive process|
|sexual reproduction|
|multicellular organism reproduction|
|peptidyl-amino acid modification|
|apoptotic process|
|negative regulation of developmental process|
|embryo development|
|central nervous system development|
|multi-organism reproductive process|
|cell cycle process|
|programmed cell death|
|chromosome organization|
|identical protein binding|
|cell death|
|cytoskeleton organization|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|cellular protein localization|
|cellular macromolecule localization|
|establishment of protein localization|
|regulation of cell population proliferation|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|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:exp343|Centrinone 0.5μM R07 exp343]]|-1.94|
|[[:results:exp392|PT-1 25μM R07 exp392]]|1.84|
|[[:results:exp475|CyclicAMP 200μM R08 exp475]]|1.9|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|1.96|
|[[:results:exp54|Taxol 0.002μM R01 exp54]]|1.97|
|[[:results:exp320|ABT-702 5μM plus CoCl2 18μM R07 exp320]]|1.98|
|[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|2.09|
|[[:results:exp59|UMK57 1μM R01 exp59]]|2.35|
</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: 69/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|0/25|
|breast|6/33|
|central nervous system|5/56|
|cervix|1/4|
|colorectal|1/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|4/21|
|liver|1/20|
|lung|9/75|
|lymphocyte|0/14|
|ovary|1/26|
|pancreas|1/24|
|peripheral nervous system|2/16|
|plasma cell|3/15|
|prostate|0/1|
|skin|1/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|2/22|
|urinary tract|6/29|
|uterus|1/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 515
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.62 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='BRCA2 Expression in NALM6 Cells: 7.62'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>