Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Brca2. (This text reflects annotations as of Thursday, January 16, 2014.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of November 16, 2007. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Brca2
  • participates in the following biological processes:
    • cellular response to DNA damage stimulus ^[4]
  • is located in the following cellular components:
    • cytoplasm ^[1]
    • nucleus ^{[1, 15]}
• The gene product of Brca2 has been shown to bind to the gene products of Rad51, Shfm1. ^{[6, 8, 15, 16, 20]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Brca2
  • participates in the following biological processes:
    • brain development ^[5]
    • cell aging ^[12]
    • cell proliferation ^{[2, 5, 10, 13, 14]}
    • chordate embryonic development ^[10]
    • chromosome organization ^{[13, 14]}
    • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator ^[11]
    • double-strand break repair ^{[2, 5]}
    • double-strand break repair via homologous recombination ^[18]
    • female gonad development ^[2]
    • hemopoiesis ^[13]
    • inner cell mass cell proliferation ^[19]
    • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator ^[7]
    • male meiosis I ^[17]
    • oocyte maturation ^[17]
    • positive regulation of mitotic cell cycle ^[14]
    • regulation of cytokinesis ^[3]
    • replication fork protection ^[9]
    • response to gamma radiation ^{[12, 16]}
    • response to UV-C ^[14]
    • response to X-ray ^{[2, 13, 14]}
    • spermatogenesis ^[2]
• Researchers have inferred, based on genetic interactions, that the gene product of Brca2
  • participates in the following biological processes:
    • intrinsic apoptotic signaling pathway in response to DNA damage based on interactions with Atm ^[5]
    • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator based on interactions with Trp53 ^[5]
  • is located in the following cellular components:
    • intracellular based on interactions with Trp53 ^[5]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Brca2:
  • participates in the following biological processes:
    • centrosome duplication
    • cytokinesis
    • DNA recombination
    • double-strand break repair
    • double-strand break repair via homologous recombination
    • histone H3 acetylation
    • histone H4 acetylation
    • homologous chromosome orientation involved in meiotic metaphase I plate congression
    • mammary gland development
    • multicellular organism growth
    • negative regulation of mammary gland epithelial cell proliferation
    • nucleotide-excision repair
    • positive regulation of transcription, DNA-templated
    • regulation of cell proliferation
    • spermatogenesis
  • performs the following molecular functions:
    • gamma-tubulin binding
    • H3 histone acetyltransferase activity
    • H4 histone acetyltransferase activity
    • protease binding
    • single-stranded DNA binding
  • is located in the following cellular components:
    • BRCA2-MAGE-D1 complex
    • centrosome
    • cytoplasm
    • nucleus
    • protein complex
    • secretory granule

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Summary text based on GO annotations supported by structural data

• Brca2 encodes a protein or proteins that contain the following InterPro domains: BRCA2 repeat, BRCA2, oligonucleotide/oligosaccharide-binding 1, BRCA2, oligonucleotide/oligosaccharide-binding 3, Breast cancer type 2 susceptibility protein, DNA recombination/repair protein BRCA2, helical domain, Nucleic acid-binding, OB-fold, Tower, indicating that the gene product:
  • participates in the following biological processes:
    • DNA repair

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Brca2 indicates that it:
  • participates in the following biological processes:
    • cell cycle
    • DNA repair
  • performs the following molecular functions:
    • DNA binding

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References

1. Bernard-Gallon DJ et al. (2001) Brca1 and Brca2 protein expression patterns in different tissues of murine origin. Int J Oncol, 18:271-80. (PubMed:11172592)
2. Connor F et al. (1997) Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. Nat Genet, 17:423-30. (PubMed:9398843)
3. Daniels MJ et al. (2004) Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science, 306:876-9. (PubMed:15375219)
4. Flores KG et al. (2002) Thymic model for examining BRCA2 expression and function. Mol Carcinog, 35:103-9. (PubMed:12410562)
5. Frappart PO et al. (2007) BRCA2 is required for neurogenesis and suppression of medulloblastoma. EMBO J, 26:2732-42. (PubMed:17476307)
6. Gudmundsdottir K et al. (2004) DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells. EMBO Rep, 5:989-93. (PubMed:15359272)
7. Hay T et al. (2005) Brca2 deficiency in the murine small intestine sensitizes to p53-dependent apoptosis and leads to the spontaneous deletion of stem cells. Oncogene, 24:3842-6. (PubMed:15735671)
8. Houghtaling S et al. (2003) Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes Dev, 17:2021-35. (PubMed:12893777)
9. Lomonosov M et al. (2003) Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein. Genes Dev, 17:3017-22. (PubMed:14681210)
10. Ludwig T et al. (1997) Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev, 11:1226-41. (PubMed:9171368)
11. Miyakawa T et al. (1996) Radial maze performance, open-field and elevated plus-maze behaviors in Fyn-kinase deficient mice: further evidence for increased fearfulness. Brain Res Mol Brain Res, 37:145-50. (PubMed:8738145)
12. Morimatsu M et al. (1998) Cells deleted for Brca2 COOH terminus exhibit hypersensitivity to gamma-radiation and premature senescence. Cancer Res, 58:3441-7. (PubMed:9699678)
13. Navarro S et al. (2006) Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1. Mol Ther, 14:525-35. (PubMed:16859999)
14. Patel KJ et al. (1998) Involvement of Brca2 in DNA repair. Mol Cell, 1:347-57. (PubMed:9660919)
15. Sarkisian CJ et al. (2001) Analysis of murine brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals. J Biol Chem, 276:37640-8. (PubMed:11477095)
16. Sharan SK et al. (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2 [see comments] Nature, 386:804-10. (PubMed:9126738)
17. Sharan SK et al. (2004) BRCA2 deficiency in mice leads to meiotic impairment and infertility. Development, 131:131-42. (PubMed:14660434)
18. Stark JM et al. (2004) Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol, 24:9305-16. (PubMed:15485900)
19. Suzuki A et al. (1997) Brca2 is required for embryonic cellular proliferation in the mouse. Genes Dev, 11:1242-52. (PubMed:9171369)
20. Yang H et al. (2002) BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science, 297:1837-48. (PubMed:12228710)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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