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breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein, BRCA2, FACD, FANCD1)

Function: - role in double-strand break repair &/or homologous recombination - may participate in S phase checkpoint activation - elevated levels at G1/S transition, remain elevated into G2 - interacts with RAD51 & DSS1 - interacts with ubiquitinated FANCD2 - interacts with PALB2 - enables the recombinational repair & checkpoints functions - interacts with WDR16 - phosphorylated by ATM upon irradiation-induced DNA damage Structure: contains 8 BRCA2 repeats Expression: - expressed in breast & thymus > lung, ovary & spleen Pathology: 1) defects in BRCA2 are a cause of genetic susceptibility to a) breast cancer b) ovarian cancer b) Fanconi anemia complementation group D type 1 2) genetic variations in BRCA2 may underlie susceptibility to uveal melanoma 3) pathogenic variants in BRCA1 & BRCA2 are associated with increased risk of - esophageal cancer - gastric cancer - biliary tract cancer - prostate cancer [8] Laboratory: - BRCA2 gene mutation - BRCA2 Ag in tissue

Interactions

molecular events

Related

breast cancer susceptibility gene-2 [BRCA-2]

General

other protein

Properties

SIZE: entity length = 3418 aa MW = 384 kD MOTIF: PALB2 interaction {1-40} Ser phosphorylation site {S683} Ser phosphorylation site {S755} BRCA2 {1002-1036} BRCA2 {1212-1246} BRCA2 {1421-1455} BRCA2 {1517-1551} BRCA2 {1664-1698} BRCA2 {1837-1871} BRCA2 {1971-2005} BRCA2 {2051-2085} FANCD2 interaction {2350-2545}

References

  1. Wooster R, Stratton MR. Breast cancer susceptibility: a complex disease unravels. Trends Genet. 1995 Jan;11(1):3-5. Review. PMID: 7900193
  2. Zhang H, Tombline G, Weber BL. BRCA1, BRCA2, and DNA damage response: collision or collusion? Cell. 1998 Feb 20;92(4):433-6. Review. PMID: 9491884
  3. Entrez Gene :accession 675
  4. Fanconi Anemia mutation Database http://www.rockefeller.edu/fanconi/mutate/jumpd1.html
  5. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA2
  6. Wikipedia; BRCA2 entry http://en.wikipedia.org/wiki/BRCA2
  7. UniProt :accession P51587
  8. Momozawa Y et al. Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants. JAMA Oncol 2022 Apr 14; [e-pub] PMID: 35420638 PMCID: PMC9011177 Free PMC article https://jamanetwork.com/journals/jamaoncology/fullarticle/2791277

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 600185 UniProt P51587 PFAM correlations Entrez Gene 675 Kegg hsa:675 Double strand break repair: homologous recombination