BRCA1 is secreted and exhibits properties of a granin

Nat Genet. 1996 Mar;12(3):303-8. doi: 10.1038/ng0396-303.


Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer. However, the function of the BRCA1 protein has remained elusive. We now show that BRCA1 encodes a 190-kD protein with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the granin consensus at the C terminus of the protein. Both BRCA1 and the granins localize to secretory vesicles, are secreted by a regulated pathway, are post-translationally glycosylated and are responsive to hormones. As a regulated secretory protein, BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • BRCA1 Protein
  • BRCA2 Protein
  • Breast / metabolism
  • Breast Neoplasms / genetics*
  • Epithelium / metabolism
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Membrane Proteins / chemistry
  • Molecular Sequence Data
  • Molecular Weight
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / genetics*
  • Proteins / chemistry
  • Rabbits
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • Antibodies
  • BRCA1 Protein
  • BRCA2 Protein
  • Membrane Proteins
  • Neoplasm Proteins
  • Proteins
  • Transcription Factors