BRISC and BRCA1-A complex member 2 (BRE)
The protein contains 383 amino acids for an estimated molecular weight of 43552 Da.
Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX (PubMed:17525341, PubMed:19261746, PubMed:19261749, PubMed:19261748). In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer (PubMed:21282113, PubMed:19261748). Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:19214193, PubMed:24075985, PubMed:25283148, PubMed:26195665). Within the BRISC complex, acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity (PubMed:21282113). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). The BRISC complex plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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
Apoptotic process
Cell cycle
Cell division
Cellular response to DNA damage stimulus
Chromatin organization
Covalent chromatin modification
Double-strand break repair
Double-strand break repair via nonhomologous end joining
G2 DNA damage checkpoint
Negative regulation of apoptotic process
Positive regulation of DNA repair
Protein deubiquitination
Protein K63-linked deubiquitination
Response to ionizing radiation
Signal transduction
Signal transduction involved in G2 DNA damage checkpoint
Cellular Component
BRCA1-A complex
BRISC complex
Cytoplasm
Cytosol
Nuclear ubiquitin ligase complex
Nucleoplasm
Nucleus
The reference OMIM entry for this protein is 610497
Brain and reproductive organ-expressed protein; bre
Brcc4
Brcc45
CLONING
Li et al. (1995) cloned BRE from a placenta cDNA library. The deduced protein contains 383 amino acids. Northern blot analysis of normal human fibroblasts detected a single BRE mRNA at 1.7 to 1.9 kb. Northern blot analysis of several rat tissues detected highest expression in testis and intermediate expression in brain and ovary. Using the juxtamembrane domain of the p55 TNF receptor (TNFRSF1A; 191190) as bait in a yeast 2-hybrid screen, Gu et al. (1998) cloned Bre from a mouse cerebellum cDNA library.GENE FUNCTION
Li et al. (1995) found that the expression of BRE decreased following DNA damage in normal human fibroblasts caused by UV irradiation or 4-nitroquinoline-1-oxide (4NQO) exposure. Similar decreased BRE expression was observed in retinoic acid-treated human brain glioma cells and promyelocytic cells. BRE expression was unchanged in cells following growth inhibition. Using protein-binding assays and immunoprecipitation analysis in HEK293 cells, Gu et al. (1998) confirmed the interaction between mouse Bre and Tnfrsf1a. Bre specifically interacted with Tnfrsf1a but not with other TNF family members. Overexpression of Bre inhibited TNF-induced NF-kappa-B activation. Dong et al. (2003) demonstrated that in human cell lines BRE and BRCC3 (300617) are components of a holoenzyme complex containing BRCA1 (113705), BRCA2 (600185), BARD1 (601593), and RAD51 (179617), which they called the BRCA1- and BRCA2-containing complex (BRCC). The complex showed UBC5 (see UBE2D1; 602961)-dependent ubiquitin E3 ligase activity. Inclusion of BRE and BRCC3 enhanced ubiquitination by the complex, and cancer-associated truncations in BRCA1 reduced the association of BRE and BRCC3 with the complex. RNA interference of BRE and BRCC3 in HeLa cells increased cell sensitivity to ionizing radiation and resulted in a defect in G2/M checkpoint arrest. Dong et al. (2003) concluded that the BRCC is a ubiquitin E3 ligase that enhances cellular survival following DNA damage.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the BRE gene to chromosome 2 (TMAP RH66226). ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610497 was added.