BRCA2Breast cancer type 2 susceptibility protein

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11239456"
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          "source": "PubMed",
          "id": "17515903"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17515904"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18317453"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19303847"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20729832"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20729858"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20729859"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21076401"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21084279"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21719596"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24485656"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24896180"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "26976601"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "27941124"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "37499663"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "37515771"
        }
      ],
      "value": "Tumor suppressor protein that maintains genome stability primarily by repairing damaged DNA through homologous recombination (HR) (PubMed:11239456, PubMed:12442171, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:15937124, PubMed:17515903, PubMed:17515904, PubMed:18317453, PubMed:19303847, PubMed:20729832, PubMed:20729858, PubMed:20729859, PubMed:21719596, PubMed:27941124, PubMed:37499663, PubMed:37515771). Facilitates the repair of double-strand breaks (DSBs) by binding and mediating the loading of the RAD51 protein onto single-stranded DNA (ssDNA), thereby promoting the activity of RAD51, which catalyzes DNA strand exchange (PubMed:11239456, PubMed:12442171, PubMed:15937124, PubMed:17515903, PubMed:17515904, PubMed:18317453, PubMed:19303847, PubMed:20729832, PubMed:20729858, PubMed:20729859, PubMed:27941124, PubMed:37499663). BRCA2 nucleates and stabilizes RAD51 on ssDNA directly and delivers RAD51 to ssDNA-double-stranded DNA (dsDNA) junctions by sliding along dsDNA backbone (PubMed:12442171, PubMed:19303847, PubMed:37499663). RAD51 targeting to ssDNA promotes removal of replication protein-A (RPA) from ssDNA and stabilization of RAD51-ssDNA filaments by blocking ATP hydrolysis (PubMed:20729859). 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 (PubMed:24485656). Required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability (PubMed:24896180). 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). Also promotes RAD51 loading to telomeric regions, facilitating telomere replication and capping (PubMed:21076401). Also required for homologous recombination during meiosis by promoting the recruitment of RAD51 and DMC1 recombinases to meiotic DSB sites, enabling proper chromosome pairing and crossing over (PubMed:26976601). Also promotes homologous recombination by inactivating the FIGNL1-FIRRM complex to protect RAD51 filament from premature disassembly (PubMed:37515771). Together with NPM1, may also regulate centrosome duplication (PubMed:21084279)"
    }
  ],
  "commentType": "FUNCTION"
}

Eukaryota → Metazoa → Chordata → Craniata → Vertebrata → Euteleostomi → Mammalia → Eutheria → Euarchontoglires → Primates → Haplorrhini → Catarrhini → Hominidae → Homo

{
  "names": {
    "recommendedName": {
      "fullName": {
        "evidences": [
          {
            "evidenceCode": "ECO:0000303",
            "source": "PubMed",
            "id": "8524414"
          }
        ],
        "value": "Breast cancer type 2 susceptibility protein"
      }
    },
    "alternativeNames": [
      {
        "fullName": {
          "evidences": [
            {
              "evidenceCode": "ECO:0000303",
              "source": "PubMed",
              "id": "15199141"
            }
          ],
          "value": "Fanconi anemia group D1 protein"
        }
      }
    ]
  },
  "genes": [
    {
      "geneName": {
        "evidences": [
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            "source": "PubMed",
            "id": "8524414"
          },
          {
            "evidenceCode": "ECO:0000312",
            "source": "HGNC",
            "id": "HGNC:1101"
          }
        ],
        "value": "BRCA2"
      },
      "synonyms": [
        {
          "value": "FACD"
        },
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000303",
              "source": "PubMed",
              "id": "15199141"
            }
          ],
          "value": "FANCD1"
        }
      ]
    }
  ]
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Breast cancer",
    "diseaseAccession": "DI-02602",
    "acronym": "BC",
    "description": "A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "114480"
    },
    "evidences": [
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        "id": "11139248"
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        "source": "PubMed",
        "id": "8640237"
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        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9150152"
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        "source": "PubMed",
        "id": "9609997"
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        "id": "9654203"
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        "source": "PubMed",
        "id": "9971877"
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    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Pancreatic cancer 2",
    "diseaseAccession": "DI-02847",
    "acronym": "PNCA2",
    "description": "A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "613347"
    },
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        "source": "PubMed",
        "id": "9140390"
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    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Breast-ovarian cancer, familial, 2",
    "diseaseAccession": "DI-02603",
    "acronym": "BROVCA2",
    "description": "A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "612555"
    },
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        "source": "PubMed",
        "id": "10584720"
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        "source": "PubMed",
        "id": "11158174"
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        "id": "7658781"
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        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9150155"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Fanconi anemia complementation group D1",
    "diseaseAccession": "DI-01601",
    "acronym": "FANCD1",
    "description": "A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "605724"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12065746"
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        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "14670928"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16825431"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17924331"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21719596"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "23108138"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Glioma 3",
    "diseaseAccession": "DI-02629",
    "acronym": "GLM3",
    "description": "Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "613029"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "15689453"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Medulloblastoma",
    "diseaseAccession": "DI-01958",
    "acronym": "MDB",
    "description": "Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "155255"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "29753700"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15199141"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15800615"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17515903"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18317453"
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      ],
      "value": "Phosphorylated by ATM upon irradiation-induced DNA damage (PubMed:15199141). Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51 (PubMed:18317453). Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination-dependent repair during S phase and G2 by inhibiting RAD51-binding (PubMed:15800615, PubMed:17515903)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15314155"
        }
      ],
      "value": "Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation (PubMed:15314155). In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation (PubMed:15314155)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8589730"
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      ],
      "value": "Highest levels of expression in breast and thymus, with slightly lower levels in lung, ovary and spleen"
    }
  ],
  "commentType": "TISSUE SPECIFICITY"
}

{
  "texts": [
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        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P97929"
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        {
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        {
          "evidenceCode": "ECO:0000269",
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        {
          "evidenceCode": "ECO:0000269",
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24896180"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "26833090"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "27941124"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28319063"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "31242413"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "37499663"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "38828772"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "39333100"
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      ],
      "value": "Monomer and dimer (PubMed:20729858). Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair (PubMed:11239456, PubMed:12442171, PubMed:15800615, PubMed:15937124, PubMed:17515904, PubMed:17515903, PubMed:18317453, PubMed:19303847, PubMed:20729832, PubMed:20729859, PubMed:21076401, PubMed:27941124, PubMed:37499663). Interacts with DMC1; regulates DMC1 recruitment and function at sites of meiotic double-strand breaks (DSBs) (PubMed:20729832, PubMed:26976601, PubMed:38828772, PubMed:39333100). Interacts with WDR16, USP11, DMC1, ROCK2 and NPM1 (PubMed:15314155, PubMed:15967112, PubMed:21084279). Interacts with SEM1; the interaction masks a nuclear export signal in BRCA2 (PubMed:10373512, PubMed:16205630, PubMed:21719596, PubMed:24013206). Interacts with both non-ubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG (PubMed:15115758, PubMed:15199141, PubMed:18212739). Part of a BRCA complex containing BRCA1, BRCA2 and PALB2 (PubMed:19369211). Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and PALB2 (PubMed:26833090). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:16793542, PubMed:19369211, PubMed:19609323, PubMed:24141787, PubMed:26833090, PubMed:28319063). Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein (PubMed:19369211). Interacts with POLH; the interaction is direct (PubMed:24485656). Interacts with the TREX-2 complex subunits PCID2 and SEM1 (PubMed:21719596, PubMed:24896180). Interacts with HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:31242413). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (By similarity)"
    }
  ],
  "commentType": "SUBUNIT"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15937124"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17515903"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17515904"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19303847"
        }
      ],
      "value": "Interacts with DMC1 and RAD51 through its eight BRCA2 repeats and its C-terminal TR2 region (PubMed:15937124, PubMed:17515903, PubMed:17515904, PubMed:19303847). The BRCA2 repeats promote RAD51 nucleation on single-stranded DNA (ssDNA) (PubMed:19303847). The TR2 region stabilizes RAD51 oligomers already assembled on ssDNA (PubMed:17515903, PubMed:17515904)"
    }
  ],
  "commentType": "DOMAIN"
}