lmmol · Proteins

Breast cancer type 2 susceptibility protein

UniProt P51587 Organism Homo sapiens Gene BRCA2, FACD, FANCD1

Also known as: BRCA2, FACD, FANCD1

Function

Tumor suppressor protein that maintains genome stability primarily by repairing damaged DNA through homologous recombination (HR). Facilitates the repair of double-strand breaks (DSBs) by binding and mediating the loading of the RAD51 protein onto single-stranded DNA (ssDNA), thereby promoting the activity of RAD51, which catalyzes DNA strand exchange. BRCA2 nucleates and stabilizes RAD51 on ssDNA directly and delivers RAD51 to ssDNA-double-stranded DNA (dsDNA) junctions by sliding along dsDNA backbone. RAD51 targeting to ssDNA promotes removal of replication protein-A (RPA) from ssDNA and stabilization of RAD51-ssDNA filaments by blocking ATP hydrolysis. 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. 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. Also promotes RAD51 loading to telomeric regions, facilitating telomere replication and capping. Also required for homologous recombination during meiosis by promoting the recruitment of RAD51 and DMC1 recombinases to meiotic DSB sites, enabling proper chromosome pairing and crossing over. Also promotes homologous recombination by inactivating the FIGNL1-FIRRM complex to protect RAD51 filament from premature disassembly. Together with NPM1, may also regulate centrosome duplication.

Classification

Family (Pfam)
PF09169 BRCA-2_helical, PF09103 BRCA-2_OB1, PF09104 BRCA-2_OB3, PF00634 BRCA2, PF22687 BRCA2_TR2, PF21318 BRCA2DBD_OB2, PF09121 Tower
InterPro
BRCA2, BRCA2_hlx, BRCA2_hlx_sf, BRCA2_OB_1, BRCA2_OB_2_dom, BRCA2_OB_3, BRCA2_repeat, BRCA2_TR2, NA-bd_OB-fold, Tower_dom
Functional cluster
Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 14

A predicted model is available from AlphaFold.

Gene Ontology · 28

Disease associations

Neighborhood · nearest proteins

BRCA2BRCA2Brca2TEX15BRCA1DMC1RAD51
Nearest neighbours of Breast cancer type 2 susceptibility protein: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 96 cited papers

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