Breast cancer type 2 susceptibility protein (BRCA2)
The protein contains 3418 amino acids for an estimated molecular weight of 384202 Da.
Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. 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. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. 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). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Brain development
Cell aging
Centrosome duplication
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
Double-strand break repair
Double-strand break repair via homologous recombination
Establishment of protein localization to telomere
Female gonad development
Hemopoiesis
Histone H3 acetylation
Histone H4 acetylation
Inner cell mass cell proliferation
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Male meiosis I
Mitotic recombination-dependent replication fork processing
Negative regulation of mammary gland epithelial cell proliferation
Nucleotide-excision repair
Oocyte maturation
Positive regulation of mitotic cell cycle
Positive regulation of transcription, DNA-templated
Regulation of cytokinesis
Regulation of transcription, DNA-templated
Replication fork protection
Response to gamma radiation
Response to UV-C
Response to X-ray
Spermatogenesis
Telomere maintenance via recombination
The reference OMIM entry for this protein is 114480
Breast cancer
Breast cancer, familial breast cancer, familial male, included
A number sign (#) is used with this entry because of evidence that mutation at more than one locus can be involved in different families or even in the same case. These loci include BRCA1 (113705) on 17q, BRCA2 (600185) on 13q12, BRCATA (600048) on 11q, BRCA3 (605365) on 13q21, BWSCR1A (602631) on 11p15.5, the TP53 gene (191170) on 17p, and the RB1CC1 gene (606837) on 8q11. Mutations in the androgen receptor gene (AR; 313700) on the X chromosome have been found in cases of male breast cancer (313700.0016). Mutation in the RAD51 gene (179617) was found in patients with familial breast cancer (179617.0001). Breast cancer susceptibility alleles have been reported in the CHEK2 gene (see 604373.0001 and 604373.0012) and in the BARD1 gene (see 601593.0001). Furthermore, the PPM1D gene (605100) on 17q is commonly amplified in breast cancer and appears to lead to cell transformation by abrogating p53 (191170) tumor suppressor activity (Bulavin et al., 2002). Somatic mutations in the PIK3CA gene (171834) and the AKT1 gene (164730) have also been identified in breast cancer. An allele of the CASP8 gene (601763.0003) has been associated with reduced risk of breast cancer. An allele of the TGFB1 gene (190180.0007) has been associated with an increased risk of invasive breast cancer. An allele of the NQO1 gene (125860.0001) has been associated with breast cancer prognosis, including survival after chemotherapy and after metastasis. Variation in the HMMR gene (600936) has also been shown to modify susceptibility. Mutations in genes responsible for various forms of Fanconi anemia (see, e.g., 227650) have been identified as susceptibility factors for breast cancer. These include BRCA2, PALB2 (610355), BRIP1 (605882), and RAD51C (602774). Breast cancer is a feature of several cancer syndromes, including Li-Fraumeni syndrome (151623) due to germline mutations in p53; Cowden syndrome (158350) due to mutations in the PTEN gene (601728); and Peutz-Jeghers syndrome (175200) due to mutations in the STK11 gene (602216). There also appears to be an increased risk of breast and ovarian cancer in ataxia-telangiectasia (208900), and there is some evidence that heterozygotes for some mutations in the ataxia-telangiectasia mutated gene (ATM; e.g., 607585.0032) have an increased risk of breast cancer. Germline and somatic mutations in the CDH1 gene (192090) have been found in lobular breast cancer and hereditary diffuse gastric cancer (LBC/HDGC; see 137215), which may represent a cancer predisposition syndrome. Some genomic regions have been found to be amplified in breast cancer, including 8q24, 20q13, 11q12, and 8p12-p11 (Yang et al., 2006). The NCOA3 (601937) and ZNF217 (602967) genes, located on 20q, undergo amplification in breast cancer; when overexpressed, these genes confer cellular phenotypes consistent with a role in tumor formation (Anzick et al., 1997; Collins et al., 1998).
DESCRIPTION
Breast cancer (referring to mammary carcinoma, not mammary sarcoma) is histopathologically and almost certainly etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement.CLINICAL FEATURES
Cady (1970) described a family in which 3 sisters had bilateral breast cancer. Together with reports in the literature, this suggested to him the existence of families with a particular tendency to early-onset, bilateral breast cancer. The genetic basis might, of course, be multifactor ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 114480 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).