BRCA1Breast cancer type 1 susceptibility protein

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10500182"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10724175"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11836499"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12183412"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12887909"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12890688"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "14976165"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16326698"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16818604"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17525340"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18056443"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19261748"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19369211"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20160719"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20351172"
        }
      ],
      "value": "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 (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). 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 (PubMed:19369211). 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 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719)"
    }
  ],
  "commentType": "FUNCTION"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform 2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Produced by alternative initiation at Met-18 of isoform 1"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform 4"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "The N-terminus is confirmed by several cDNAs"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform 8"
}

{
  "texts": [
    {
      "value": "Protein modification; protein ubiquitination"
    }
  ],
  "commentType": "PATHWAY"
}

{
  "commentType": "CATALYTIC ACTIVITY",
  "reaction": {
    "name": "S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.",
    "ecNumber": "2.3.2.27",
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "10500182"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12887909"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12890688"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16818604"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "18056443"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20351172"
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18056443"
        }
      ],
      "value": "The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment"
    }
  ],
  "commentType": "ACTIVITY REGULATION"
}

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

{
  "names": {
    "recommendedName": {
      "fullName": {
        "value": "Breast cancer type 1 susceptibility protein"
      },
      "ecNumbers": [
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "10500182"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "12887909"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "12890688"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "16818604"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "18056443"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "20351172"
            }
          ],
          "value": "2.3.2.27"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "RING finger protein 53"
        }
      },
      {
        "fullName": {
          "evidences": [
            {
              "evidenceCode": "ECO:0000305"
            }
          ],
          "value": "RING-type E3 ubiquitin transferase BRCA1"
        }
      }
    ]
  },
  "genes": [
    {
      "geneName": {
        "value": "BRCA1"
      },
      "synonyms": [
        {
          "value": "RNF53"
        }
      ]
    }
  ]
}

{
  "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": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "10323242"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "11114888"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "11301010"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12427738"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12442275"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12938098"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "14722926"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "15133502"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "18285836"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21473589"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "23867111"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28364669"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7545954"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7894491"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7894493"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7939630"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8554067"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8723683"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8776600"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8807330"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9482581"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9609997"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9760198"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Breast-ovarian cancer, familial, 1",
    "diseaseAccession": "DI-01559",
    "acronym": "BROVCA1",
    "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": "604370"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12938098"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "14722926"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17924331"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20513136"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28364669"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8968716"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Ovarian cancer",
    "diseaseAccession": "DI-01655",
    "acronym": "OC",
    "description": "The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "167000"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "10196379"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "10486320"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "14746861"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28364669"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Pancreatic cancer 4",
    "diseaseAccession": "DI-03281",
    "acronym": "PNCA4",
    "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": "614320"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "18762988"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Fanconi anemia, complementation group S",
    "diseaseAccession": "DI-05209",
    "acronym": "FANCS",
    "description": "A form of Fanconi anemia, 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": "617883"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "23269703"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "25472942"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "29133208"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "texts": [
    {
      "value": "There is evidence that the presence of the rare form of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer"
    }
  ],
  "commentType": "POLYMORPHISM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10724175"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11114888"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12183412"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18056443"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20364141"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21144835"
        }
      ],
      "value": "Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR (PubMed:11114888, PubMed:12183412, PubMed:21144835). Phosphorylation at Ser-988 by CHEK2 regulates mitotic spindle assembly (PubMed:10724175, PubMed:20364141). Phosphorylation by AURKA regulates centrosomal microtubule nucleation (PubMed:18056443)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12890688"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20351172"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23086937"
        }
      ],
      "value": "Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation. Ubiquitinated in a FBXO44-dependent manner; leading to proteasomal degradation (PubMed:23086937)"
    }
  ],
  "commentType": "PTM"
}