BRCA1 [The Human Chemical-Genetic Interaction Map Project]

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======= BRCA1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: BRCA1
  * **<color #00a2e8>Official Name</color>**: BRCA1 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=672|672]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P38398|P38398]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=BRCA1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20BRCA1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/113705|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]. 
  * **<color #00a2e8>UniProt Summary</color>**:  E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:20364141}.

<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'>
|zf-C3HC4|
|BRCT assoc|
|BRCT|
|EIN3|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of histone H4-K20 methylation|
|positive regulation of histone H4-K20 methylation|
|BRCA1-BARD1 complex|
|positive regulation of histone H4-K16 acetylation|
|cellular response to indole-3-methanol|
|negative regulation of histone H3-K4 methylation|
|response to indole-3-methanol|
|BRCA1-A complex|
|regulation of histone H4-K16 acetylation|
|positive regulation of histone H4 acetylation|
|negative regulation of centriole replication|
|positive regulation of histone H3-K9 acetylation|
|protein K6-linked ubiquitination|
|gamma-tubulin ring complex|
|negative regulation of histone H3-K9 methylation|
|positive regulation of histone H3-K9 methylation|
|signal transduction involved in G2 DNA damage checkpoint|
|negative regulation of centrosome duplication|
|regulation of histone H4 acetylation|
|lateral element|
|regulation of histone H3-K9 acetylation|
|negative regulation of centrosome cycle|
|negative regulation of intracellular estrogen receptor signaling pathway|
|DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator|
|DNA damage response, signal transduction resulting in transcription|
|negative regulation of histone acetylation|
|negative regulation of fatty acid biosynthetic process|
|RNA polymerase binding|
|positive regulation of histone H3-K4 methylation|
|dosage compensation by inactivation of X chromosome|
|negative regulation of peptidyl-lysine acetylation|
|regulation of gene expression by genetic imprinting|
|dosage compensation|
|negative regulation of histone methylation|
|negative regulation of protein acetylation|
|DNA double-strand break processing|
|regulation of centriole replication|
|regulation of histone H3-K9 methylation|
|regulation of transcription by RNA polymerase III|
|genetic imprinting|
|regulation of DNA methylation|
|negative regulation of fatty acid metabolic process|
|regulation of histone H3-K4 methylation|
|mitotic G2/M transition checkpoint|
|positive regulation of vascular endothelial growth factor production|
|G2 DNA damage checkpoint|
|positive regulation of histone acetylation|
|regulation of vascular endothelial growth factor production|
|positive regulation of peptidyl-lysine acetylation|
|androgen receptor signaling pathway|
|negative regulation of intracellular steroid hormone receptor signaling pathway|
|negative regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|negative regulation of organelle assembly|
|negative regulation of G0 to G1 transition|
|positive regulation of histone methylation|
|negative regulation of histone modification|
|positive regulation of protein acetylation|
|regulation of intracellular estrogen receptor signaling pathway|
|regulation of centrosome duplication|
|regulation of G0 to G1 transition|
|androgen receptor binding|
|regulation of fatty acid biosynthetic process|
|negative regulation of lipid biosynthetic process|
|postreplication repair|
|tubulin binding|
|negative regulation of reactive oxygen species metabolic process|
|regulation of histone acetylation|
|damaged DNA binding|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|double-strand break repair via nonhomologous end joining|
|regulation of centrosome cycle|
|negative regulation of chromatin organization|
|regulation of peptidyl-lysine acetylation|
|non-recombinational repair|
|protein autoubiquitination|
|regulation of histone methylation|
|positive regulation of DNA repair|
|intracellular steroid hormone receptor signaling pathway|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|regulation of protein acetylation|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in cell cycle checkpoint|
|response to estrogen|
|regulation of intracellular steroid hormone receptor signaling pathway|
|DNA damage response, signal transduction by p53 class mediator|
|positive regulation of cell cycle arrest|
|centrosome cycle|
|negative regulation of lipid metabolic process|
|cellular response to alcohol|
|regulation of fatty acid metabolic process|
|negative regulation of G2/M transition of mitotic cell cycle|
|positive regulation of histone modification|
|negative regulation of small molecule metabolic process|
|microtubule organizing center organization|
|response to antineoplastic agent|
|double-strand break repair via homologous recombination|
|recombinational repair|
|positive regulation of response to DNA damage stimulus|
|negative regulation of cell cycle G2/M phase transition|
|negative regulation of extrinsic apoptotic signaling pathway|
|positive regulation of chromatin organization|
|signal transduction in response to DNA damage|
|ubiquitin ligase complex|
|regulation of cell cycle arrest|
|positive regulation of protein ubiquitination|
|fatty acid biosynthetic process|
|steroid hormone mediated signaling pathway|
|signal transduction by p53 class mediator|
|chromosome|
|regulation of DNA repair|
|DNA damage checkpoint|
|negative regulation of chromosome organization|
|positive regulation of protein modification by small protein conjugation or removal|
|negative regulation of cytoskeleton organization|
|DNA integrity checkpoint|
|regulation of histone modification|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|mitotic cell cycle checkpoint|
|regulation of extrinsic apoptotic signaling pathway|
|ribonucleoprotein complex|
|intracellular receptor signaling pathway|
|positive regulation of angiogenesis|
|hormone-mediated signaling pathway|
|regulation of cellular ketone metabolic process|
|positive regulation of chromosome organization|
|regulation of reactive oxygen species metabolic process|
|regulation of signal transduction by p53 class mediator|
|double-strand break repair|
|positive regulation of vasculature development|
|monocarboxylic acid biosynthetic process|
|regulation of lipid biosynthetic process|
|cellular response to steroid hormone stimulus|
|regulation of chromatin organization|
|regulation of microtubule cytoskeleton organization|
|cell cycle checkpoint|
|positive regulation of DNA metabolic process|
|regulation of G2/M transition of mitotic cell cycle|
|regulation of protein ubiquitination|
|regulation of cell cycle G2/M phase transition|
|negative regulation of mitotic cell cycle phase transition|
|DNA replication|
|transcription regulatory region DNA binding|
|regulation of response to DNA damage stimulus|
|regulation of organelle assembly|
|DNA recombination|
|regulation of microtubule-based process|
|negative regulation of apoptotic signaling pathway|
|regulation of protein modification by small protein conjugation or removal|
|negative regulation of cell cycle phase transition|
|response to alcohol|
|regulation of gene expression, epigenetic|
|cellular response to tumor necrosis factor|
|ubiquitin-protein transferase activity|
|response to tumor necrosis factor|
|chromosome segregation|
|protein deubiquitination|
|transcription coactivator activity|
|apoptotic signaling pathway|
|positive regulation of cell cycle process|
|regulation of angiogenesis|
|ubiquitin protein ligase binding|
|protein modification by small protein removal|
|protein polyubiquitination|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|negative regulation of mitotic cell cycle|
|regulation of vasculature development|
|fatty acid metabolic process|
|negative regulation of cell cycle process|
|response to steroid hormone|
|enzyme binding|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|negative regulation of organelle organization|
|positive regulation of cell cycle|
|regulation of lipid metabolic process|
|regulation of apoptotic signaling pathway|
|cellular response to drug|
|regulation of mitotic cell cycle phase transition|
|regulation of small molecule metabolic process|
|response to radiation|
|regulation of cell cycle phase transition|
|positive regulation of cytokine production|
|microtubule cytoskeleton organization|
|DNA repair|
|cellular response to lipid|
|monocarboxylic acid metabolic process|
|regulation of cytoskeleton organization|
|cellular response to organic cyclic compound|
|negative regulation of cell cycle|
|lipid biosynthetic process|
|small molecule biosynthetic process|
|negative regulation of protein modification process|
|protein-containing complex|
|mitotic cell cycle process|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|embryo development ending in birth or egg hatching|
|cellular response to nitrogen compound|
|microtubule-based process|
|mitotic cell cycle|
|protein ubiquitination|
|regulation of cytokine production|
|negative regulation of cellular component organization|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|zinc ion binding|
|response to lipid|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|carboxylic acid metabolic process|
|response to organic cyclic compound|
|apoptotic process|
|cellular lipid metabolic process|
|regulation of cellular component biogenesis|
|embryo development|
|protein modification by small protein conjugation or removal|
|negative regulation of cell death|
|cell cycle process|
|response to organonitrogen compound|
|oxoacid metabolic process|
|cellular response to cytokine stimulus|
|response to drug|
|organic acid metabolic process|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|response to nitrogen compound|
|cell death|
|response to cytokine|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|macromolecule biosynthetic process|
|regulation of intracellular signal transduction|
|regulation of protein modification 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='primary' 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:exp474|CR131-b 0.005μM R08 exp474]]|-2.09|
|[[:results:exp442|Ibrutinib 10μM R08 exp442]]|-1.86|
|[[:results:exp495|IWR1 50μM R08 exp495]]|-1.84|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|-1.74|
|[[:results:exp224|CB-839 10μM R05 exp224]]|-1.72|
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|-1.7|
|[[:results:exp218|A-395 10μM R05 exp218]]|1.7|
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|1.73|
|[[:results:exp149|SB203580 25μM R03 exp149]]|1.8|
|[[:results:exp151|SGC0946 7μM R03 exp151]]|1.84|
|[[:results:exp114|A-196 10μM R03 exp114]]|2.14|
|[[:results:exp122|Golgicide-A 4μM R03 exp122]]|2.14|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.417|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 43/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|2/28|
|blood|1/28|
|bone|1/25|
|breast|6/33|
|central nervous system|5/56|
|cervix|0/4|
|colorectal|1/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|1/21|
|liver|1/20|
|lung|3/75|
|lymphocyte|0/14|
|ovary|2/26|
|pancreas|0/24|
|peripheral nervous system|1/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|3/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|1/22|
|urinary tract|1/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 618
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.37 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='BRCA1 Expression in NALM6 Cells: 7.37'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>