Breast cancer type 2 susceptibility protein - P51587 (BRCA2_HUMAN)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

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). UniProt
Pathway Maps
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Subunit Structure
Monomer and dimer (PubMed:20729858). Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair (PubMed:12442171, PubMed:15800615, PubMed:18317453, PubMed:20729832, PubMed:20729859). Interacts with WDR16, USP11, DMC1, ROCK2 and NPM1 (PubMed:15314155, PubMed:15967112, PubMed:20729832, PubMed:21084279). Interacts with SEM1; the interaction masks a nuclear export signal in BRCA2 (PubMed:10373512, PubMed:16205630, PubMed:21719596, PubMed:24013206). Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG (PubMed:15115758, PubMed:15199141, PubMed:18212739). Part of a BRCA complex containing BRCA1, BRCA2 and PALB2 (PubMed:19369211). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:19369211, PubMed:24141787, PubMed:28319063, PubMed:16793542, PubMed:19609323). Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein (PubMed:19369211). Interacts with POLH; the interaction is direct (PubMed:24485656). Interacts with the TREX-2 complex subunits PCID2 and SEM1 (PubMed:24896180, PubMed:21719596). UniProt
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The PDB to UniProt mapping is based on the data provided by the EBI SIFTS project. See also Velankar et al., Nucleic Acids Research 33, D262-265 (2005).
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