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BRCA1 the BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Plays a central role in DNA repair by facilitating cellular response to DNA repair. 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 ACC1 and preventing its dephosphorylation. Defects in BRCA1 are a cause of genetic susceptibility to breast cancer. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association may be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts (via BRCT domains) with CTIP. Associates with RNA polymerase II holoenzyme. Interacts with SMC1 and COBRA1. Interacts (via BRCT domains) with BRIP1. Interacts with FANCD2 (ubiquitinated). Interacts with BAP1. Interacts with Artemis and claspin. Interacts with H2AFX (phosphorylated on S140). Interacts with CHK1. Interacts with BRCC3. Five human isoforms are produced by alternative splicing and alternative initiation. Isoform 1 and isoform 3 are widely expressed. Isoform 1 is largely nuclear, while isoforms 3 and 5 are cytoplasmic. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; Nuclear receptor co-regulator; Transcription, coactivator/corepressor; Tumor suppressor; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 17q21.31
Cellular Component: BRCA1-BARD1 complex; chromosome; cytoplasm; lateral element; nucleoplasm; nucleus; plasma membrane; protein complex; ribonucleoprotein complex
Molecular Function: DNA binding; enzyme binding; protein binding; RNA binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity
Biological Process: apoptosis; chordate embryonic development; chromosome segregation; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; DNA damage response, signal transduction resulting in induction of apoptosis; DNA double-strand break processing; DNA replication; DNA synthesis during DNA repair; dosage compensation, by inactivation of X chromosome; double-strand break repair; double-strand break repair via homologous recombination; double-strand break repair via nonhomologous end joining; G2/M transition DNA damage checkpoint; negative regulation of estrogen receptor signaling pathway; negative regulation of fatty acid biosynthetic process; negative regulation of histone acetylation; negative regulation of histone H3-K9 methylation; negative regulation of transcription, DNA-dependent; positive regulation of angiogenesis; positive regulation of DNA repair; positive regulation of histone acetylation; positive regulation of histone H3-K4 methylation; positive regulation of protein ubiquitination; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; postreplication repair; protein autoubiquitination; protein deubiquitination; protein ubiquitination; regulation of apoptosis; regulation of cell proliferation; regulation of transcription from RNA polymerase II promoter; regulation of transcription from RNA polymerase III promoter; response to DNA damage stimulus; response to estrogen stimulus; response to ionizing radiation; strand displacement
Disease: Breast Cancer; Breast-ovarian Cancer, Familial, Susceptibility To, 1; Pancreatic Cancer, Susceptibility To, 4
Reference #:  P38398 (UniProtKB)
Alt. Names/Synonyms: BRCA1; BRCA1/BRCA2-containing complex, subunit 1; BRCAI; BRCC1; breast and ovarian cancer susceptibility protein 1; breast and ovarian cancer sususceptibility protein; breast cancer 1, early onset; Breast cancer type 1 susceptibility protein; BROVCA1; IRIS; PSCP; RING finger protein 53; RNF53
Gene Symbols: BRCA1
Molecular weight: 207,721 Da
Basal Isoelectric point: 5.29  Predict pI for various phosphorylation states
CST Pathways:  G2/M DNA Damage Checkpoint  |  Protein Acetylation
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