BRCA1

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]

BRCA1, DNA Repair Associated

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:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:12887909, PubMed:10500182, 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:12183412, PubMed:11836499, 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).

Cellular response to DNA damage stimulus Source: ProtInc
Cellular response to indole-3-methanol Source: UniProtKB
Cellular response to tumor necrosis factor Source: BHF-UCL
Centrosome cycle Source: Ensembl
Chordate embryonic development Source: GO_Central
Chromosome segregation Source: UniProtKB
DNA double-strand break processing Source: Reactome
DNA replication Source: Reactome
Dosage compensation by inactivation of X chromosome Source: GO_Central
Double-strand break repair Source: CACAO
Double-strand break repair via homologous recombination Source: HGNC-UCL
Double-strand break repair via nonhomologous end joining Source: Reactome
Fatty acid biosynthetic process Source: UniProtKB-KW
Intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
Mitotic G2/M transition checkpoint Source: Ensembl
Negative regulation of centriole replication Source: UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
Negative regulation of fatty acid biosynthetic process Source: UniProtKB
Negative regulation of G0 to G1 transition Source: Reactome
Negative regulation of histone acetylation Source: GO_Central
Negative regulation of histone H3-K4 methylation Source: Ensembl
Negative regulation of histone H3-K9 methylation Source: BHF-UCL
Negative regulation of intracellular estrogen receptor signaling pathway Source: CACAO
Negative regulation of reactive oxygen species metabolic process Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of angiogenesis Source: BHF-UCL
Positive regulation of cell cycle arrest Source: BHF-UCL
Positive regulation of DNA repair Source: UniProtKB
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of histone acetylation Source: BHF-UCL
Positive regulation of histone H3-K4 methylation Source: BHF-UCL
Positive regulation of histone H3-K9 acetylation Source: BHF-UCL
Positive regulation of histone H3-K9 methylation Source: Ensembl
Positive regulation of histone H4-K16 acetylation Source: BHF-UCL
Positive regulation of histone H4-K20 methylation Source: BHF-UCL
Positive regulation of protein ubiquitination Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of vascular endothelial growth factor production Source: BHF-UCL
Postreplication repair Source: HGNC-UCL
Protein autoubiquitination Source: UniProtKB
Protein deubiquitination Source: Reactome
Protein K6-linked ubiquitination Source: UniProtKB
Protein ubiquitination Source: HGNC-UCL
Regulation of DNA methylation Source: Ensembl
Regulation of gene expression by genetic imprinting Source: Ensembl
Regulation of signal transduction by p53 class mediator Source: Reactome
Regulation of transcription by RNA polymerase II Source: UniProtKB
Response to estrogen Source: UniProtKB
Response to ionizing radiation Source: UniProtKB
Signal transduction involved in G2 DNA damage checkpoint Source: UniProtKB

Cytoplasm; Nucleus; Chromosome. Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by ABRAXAS1 and the BRCA1-A complex (PubMed:26778126). Translocated to the cytoplasm during UV-induced apoptosis (PubMed:20160719).
Isoform 3: Cytoplasm
Isoform 5: Cytoplasm

Breast cancer (BC): 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. 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.
Breast-ovarian cancer, familial, 1 (BROVCA1): 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. 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.
Ovarian cancer (OC): 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.
Pancreatic cancer 4 (PNCA4): 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.
Fanconi anemia, complementation group S (FANCS): 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.

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).
Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.