BRISC and BRCA1-A complex member 1 (BABAM1)
The protein contains 329 amino acids for an estimated molecular weight of 36560 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. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). 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 cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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
Cell cycle
Cell division
Chromatin organization
Covalent chromatin modification
Double-strand break repair
Double-strand break repair via nonhomologous end joining
G2 DNA damage checkpoint
Hematopoietic stem cell proliferation
Positive regulation of DNA repair
Protein deubiquitination
Protein K63-linked deubiquitination
Response to ionizing radiation
Signal transduction involved in G2 DNA damage checkpoint
Molecular Function
The reference OMIM entry for this protein is 612766
Chromosome 19 open reading frame 62; c19orf62
Mediator of rap80 interactions and targeting, 40-kd; merit40
New component of brca1 a complex 1; nba1
CLONING
Using mass spectrometry to identify components of a BRCA1 (113705)-associated DNA repair complex, Feng et al. (2009) and Shao et al. (2009) independently identified MERIT40. The deduced protein contains 329 amino acids and has a calculated molecular mass of about 36.5 kD. Using a genetic screen, Wang et al. (2009) identified NBA1 as a gene required for resistance to ionizing radiation (IR). NBA1 contains a von Willebrand factor (VWF; 613160) type A (VWA) domain homologous to the VWA domain of the proteasome subunit PSMD4 (601648).GENE FUNCTION
Using coimmunoprecipitation assays, Feng et al. (2009) confirmed that MERIT40 was part of a BRCA1-associated protein complex containing BRE (610497), BRCC36 (BRCC3; 300617), CCDC98 (611143), and RAP80 (UIMC1; 609433). The C-terminal regions of MERIT40 and BRE interacted directly, and the interaction stabilized BRE against degradation. The MERIT40-BRE interaction also stabilized the entire protein complex, which was required for efficient BRCA1 foci formation and function at sites of DNA damage. Wang et al. (2009) found that NBA1 was part of a BRCA1-associated complex in human cell lines and was required for BRCA1 focus formation. Knockdown of NBA1 via short hairpin RNA led to increased sensitivity of cells to DNA damage caused by IR, ultraviolet radiation, and chemical DNA-damaging agents. NBA1-depleted human osteosarcoma cells were unable to arrest efficiently in G2 in response to IR. Similar to BRE, NBA1 was incorporated into the BRCA1-associated complex via the N-terminal region of ABRA1 (CCDC98), which then mediated the interaction of NBA1 and BRE with RAP80 and BRCC36. RAP80 targets BRCA1-associated complex components, including the deubiquitinating enzyme BRCC36, to polyubiquitin structures at DNA double-strand breaks (DSBs). Shao et al. (2009) identified MERIT40 as a RAP80-associated protein essential for BRCA1-RAP80 complex protein interactions, stability, and DSB targeting. Moreover, MERIT40 was required for RAP80-associated deubiquitinating activity of BRCC36, a critical component of viability responses to IR. Shao et al. (2009) concluded that MERIT40 links BRCA1-RAP80 complex integrity, DSB recognition, and ubiquitin chain hydrolysis to the DNA damage response.MAPPING
Hartz (2009) mapped the C19ORF62 gene to chromosome 19p13.11 based on an alignment of the C19ORF62 sequence (GenBank GENBANK AF161491) with the genomic sequence (build 36.1). ... 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 612766 was added.