Breast Cancer Susceptibility Protein 1 (BRCA1)

BRCAI; BRCC1; IRIS; PSCP; RNF53; Breast Cancer 1,Early Onset; RING finger protein 53

SPN	V457
HGNC	1100
MGI	104537
PubMed	12767038
RGD	2218
UniProt	P38398
Wiki	BRCA1

BRCA1  is a human gene, some mutations of which are associated with a significant increase in the risk of breast cancer, as well as other cancers. BRCA1 belongs to a class of genes known as tumor suppressors, which maintains genomic integrity to prevent dangerous genetic changes. The multifactorial BRCA1 protein product is involved in DNA damage repair especially error-free repair of DNA double strand breaks, ubiquitination, transcriptional regulation as well as other functions.The BRCA1 protein is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein is thought to interact indirectly with RAD51 during repair of DNA double-strand breaks, though the details and significance of this interaction is the subject of debate.

Reference

"A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1."
Science 266:66-71(1994) [PubMed] [Europe PMC] [Abstract]

"Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1."
Genome Res. 6:1029-1049(1996) [PubMed] [Europe PMC] [Abstract]

"Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-delta11b."
Oncogene 14:1-16(1997) [PubMed] [Europe PMC] [Abstract]

"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Initiation of translation from a downstream in-frame AUG codon on BRCA1 can generate the novel isoform protein DeltaBRCA1(17aa)."
Oncogene 19:2767-2773(2000) [PubMed] [Europe PMC] [Abstract]

"Localization of BRCA1 and a splice variant identifies the nuclear localization signal."
Mol. Cell. Biol. 17:444-452(1997) [PubMed] [Europe PMC] [Abstract]

"BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression."
Oncogene 16:1097-1112(1998) [PubMed] [Europe PMC] [Abstract]

"Characterization of a carboxy-terminal BRCA1 interacting protein."
Oncogene 17:2279-2285(1998) [PubMed] [Europe PMC] [Abstract]

"RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination."
Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999) [PubMed] [Europe PMC] [Abstract]

"BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures."
Genes Dev. 14:927-939(2000) [PubMed] [Europe PMC] [Abstract]

"Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress."
Genes Dev. 14:2989-3002(2000) [PubMed] [Europe PMC] [Abstract]

"hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response."
Nature 404:201-204(2000) [PubMed] [Europe PMC] [Abstract]

"BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function."
Cell 105:149-160(2001) [PubMed] [Europe PMC] [Abstract]

"BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations."
J. Cell Biol. 155:911-921(2001) [PubMed] [Europe PMC] [Abstract]

"Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway."
Mol. Cell 7:249-262(2001) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of serine 1387 in BRCA1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation."
Cancer Res. 62:4588-4591(2002) [PubMed] [Europe PMC] [Abstract]

"NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain."
Curr. Biol. 12:1846-1851(2002) [PubMed] [Europe PMC] [Abstract]

"SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint."
Genes Dev. 16:571-582(2002) [PubMed] [Europe PMC] [Abstract]

"The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity."
J. Biol. Chem. 277:7849-7856(2002) [PubMed] [Europe PMC] [Abstract]

"BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage."
Nat. Genet. 30:285-289(2002) [PubMed] [Europe PMC] [Abstract]

"BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains."
Oncogene 21:6729-6739(2002) [PubMed] [Europe PMC] [Abstract]

"The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin."
J. Biol. Chem. 278:34743-34746(2003) [PubMed] [Europe PMC] [Abstract]

"BRCA1-independent ubiquitination of FANCD2."
Mol. Cell 12:247-254(2003) [PubMed] [Europe PMC] [Abstract]

"Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair."
Mol. Cell 12:1087-1099(2003) [PubMed] [Europe PMC] [Abstract]

"BRCA1:BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair."
Hum. Mol. Genet. 13:807-817(2004) [PubMed] [Europe PMC] [Abstract]

"BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition."
J. Biol. Chem. 279:19643-19648(2004) [PubMed] [Europe PMC] [Abstract]

"Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response."
Mol. Cell. Biol. 24:9207-9220(2004) [PubMed] [Europe PMC] [Abstract]

"Human claspin works with BRCA1 to both positively and negatively regulate cell proliferation."
Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP."
Genes Dev. 20:1721-1726(2006) [PubMed] [Europe PMC] [Abstract]

"BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase."
J. Biol. Chem. 281:3172-3181(2006) [PubMed] [Europe PMC] [Abstract]

"ACCA phosphopeptide recognition by the BRCT repeats of BRCA1."
J. Mol. Biol. 359:973-982(2006) [PubMed] [Europe PMC] [Abstract]

"Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation."
Cancer Res. 67:11186-11194(2007) [PubMed] [Europe PMC] [Abstract]

"CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response."
Nat. Struct. Mol. Biol. 14:710-715(2007) [PubMed] [Europe PMC] [Abstract]

"CCDC98 targets BRCA1 to DNA damage sites."
Nat. Struct. Mol. Biol. 14:716-720(2007) [PubMed] [Europe PMC] [Abstract]

"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]

"Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response."
Science 316:1194-1198(2007) [PubMed] [Europe PMC] [Abstract]

"Germline BRCA1 mutations predispose to pancreatic adenocarcinoma."
Hum. Genet. 124:271-278(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"MERIT40 facilitates BRCA1 localization and DNA damage repair."
Genes Dev. 23:719-728(2009) [PubMed] [Europe PMC] [Abstract]

"NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control."
Genes Dev. 23:729-739(2009) [PubMed] [Europe PMC] [Abstract]

"MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks."
Genes Dev. 23:740-754(2009) [PubMed] [Europe PMC] [Abstract]

"PALB2 is an integral component of the BRCA complex required for homologous recombination repair."
Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function."
Mol. Cell. Biol. 30:2787-2798(2010) [PubMed] [Europe PMC] [Abstract]

"The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells."
Nat. Cell Biol. 12:492-499(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Protein phosphatase 5 is necessary for ATR-mediated DNA repair."
Biochem. Biophys. Res. Commun. 404:476-481(2011) [PubMed] [Europe PMC] [Abstract]

"KIAA0101 interacts with BRCA1 and regulates centrosome number."
Mol. Cancer Res. 9:1091-1099(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"Structure of a BRCA1-BARD1 heterodimeric RING-RING complex."
Nat. Struct. Biol. 8:833-837(2001) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1."
Nat. Struct. Biol. 8:838-842(2001) [PubMed] [Europe PMC] [Abstract]

"Structural consequences of a cancer-causing BRCA1-BRCT missense mutation."
J. Biol. Chem. 278:2630-2635(2003) [PubMed] [Europe PMC] [Abstract]

"Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1."
Biochemistry 43:15983-15995(2004) [PubMed] [Europe PMC] [Abstract]

"Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer."
Nat. Struct. Mol. Biol. 11:512-518(2004) [PubMed] [Europe PMC] [Abstract]

"Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex."
Biochemistry 44:10941-10946(2005) [PubMed] [Europe PMC] [Abstract]

"Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho-peptide from human ACC1."
Biochemistry 47:5767-5773(2008) [PubMed] [Europe PMC] [Abstract]

"Pathogenicity of the BRCA1 missense variant M1775K is determined by the disruption of the BRCT phosphopeptide-binding pocket: a multi-modal approach."
Eur. J. Hum. Genet. 16:820-832(2008) [PubMed] [Europe PMC] [Abstract]

"Comparison of the structures and peptide binding specificities of the BRCT domains of MDC1 and BRCA1."
Structure 18:167-176(2010) [PubMed] [Europe PMC] [Abstract]

"Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene."
Hum. Mutat. 8:8-18(1996) [PubMed] [Europe PMC] [Abstract]

"BRCA1 mutations in primary breast and ovarian carcinomas."
Science 266:120-122(1994) [PubMed] [Europe PMC] [Abstract]

"Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer."
Nat. Genet. 8:387-391(1994) [PubMed] [Europe PMC] [Abstract]

"Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families."
Nat. Genet. 8:399-404(1994) [PubMed] [Europe PMC] [Abstract]

"A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families."
Am. J. Hum. Genet. 58:42-51(1996) [PubMed] [Europe PMC] [Abstract]

"BRCA1 R841W: a strong candidate for a common mutation with moderate phenotype."
Genet. Epidemiol. 13:595-604(1996) [PubMed] [Europe PMC] [Abstract]

"Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations."
Hum. Mol. Genet. 5:835-842(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in the BRCA1 gene in Japanese breast cancer patients."
Hum. Mutat. 7:334-339(1996) [PubMed] [Europe PMC] [Abstract]

"A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene."
Hum. Genet. 103:154-161(1998) [PubMed] [Europe PMC] [Abstract]

"Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening."
Hum. Mutat. 11:166-174(1998) [PubMed] [Europe PMC] [Abstract]

"High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families."
J. Hum. Genet. 43:42-48(1998) [PubMed] [Europe PMC] [Abstract]

"The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes."
Am. J. Hum. Genet. 65:1021-1029(1999) [PubMed] [Europe PMC] [Abstract]

"Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan."
Hum. Genet. 104:201-204(1999) [PubMed] [Europe PMC] [Abstract]

"Germline BRCA1 alterations in a population-based series of ovarian cancer cases."
Hum. Mol. Genet. 8:889-897(1999) [PubMed] [Europe PMC] [Abstract]

"Characterization of common BRCA1 and BRCA2 variants."
Genet. Test. 6:119-121(2002) [PubMed] [Europe PMC] [Abstract]

"BRCA1 and BRCA2 sequence variants in Chinese breast cancer families."
Hum. Mutat. 20:474-474(2002) [PubMed] [Europe PMC] [Abstract]

"BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico."
Hum. Mutat. 20:474-475(2002) [PubMed] [Europe PMC] [Abstract]

"Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany."
Hum. Mutat. 22:259-259(2003) [PubMed] [Europe PMC] [Abstract]

"BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families."
Br. J. Cancer 90:1244-1251(2004) [PubMed] [Europe PMC] [Abstract]

"One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden."
Eur. J. Cancer 40:422-428(2004) [PubMed] [Europe PMC] [Abstract]

"Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast-ovarian cancer families."
Hum. Mutat. 23:205-205(2004) [PubMed] [Europe PMC] [Abstract]

"BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer."
Hum. Mutat. 24:350-350(2004) [PubMed] [Europe PMC] [Abstract]

"The consensus coding sequences of human breast and colorectal cancers."
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]

"A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes."
Am. J. Hum. Genet. 81:873-883(2007) [PubMed] [Europe PMC] [Abstract]

"Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity."
Hum. Mutat. 31:E1484-E1505(2010) [PubMed] [Europe PMC] [Abstract]

"A high-throughput functional complementation assay for classification of BRCA1 missense variants."
Cancer Discov. 3:1142-1155(2013) [PubMed] [Europe PMC] [Abstract]