Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway

Nature. 1990 Sep 20;347(6290):291-4. doi: 10.1038/347291a0.


Neurofibromatosis type-1 (NF-1) is one of the most frequently inherited genetic disorders affecting humans. NF-1 primarily affects cells of neural crest origin and is characterized by patches of skin pigmentation (café-au-lait spots) and neurofibromas. Cloning of the human NF-1 gene shows that it encodes an 11-13 kilobase transcript that is frequently disrupted in NF-1 patients. The frequent disruption of the NF-1 gene in NF-1 patients combined with the autosomal dominant mode of inheritance of NF-1 strongly suggest that the NF-1 gene is a tumour-suppressor gene. We have now sequenced a portion of the murine NF-1 gene and show that the predicted amino-acid sequence is nearly the same as the corresponding region of the human NF-1 gene product. Northern blotting identified mouse NF-1 transcripts that are equivalent in size and complexity to those in human tissues, and Southern blotting shows that this region of the NF-1 gene is evolutionarily well conserved. Finally, computer searches identified homology between the mouse NF-1 gene and IRA-1 and IRA-2, two genes identified in Saccharomyces cerevisiae that negatively regulate the RAS-cyclic AMP pathway. These findings provide important new insights into the possible function of the NF-1 gene.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence*
  • Cyclic AMP / biosynthesis*
  • Fungal Proteins / genetics*
  • GTPase-Activating Proteins
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neurofibromatosis 1 / genetics*
  • Nucleic Acid Hybridization
  • Proteins / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Repressor Proteins*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Nucleic Acid*
  • Suppression, Genetic
  • ras GTPase-Activating Proteins


  • Fungal Proteins
  • GTPase-Activating Proteins
  • IRA1 protein, S cerevisiae
  • IRA2 protein, S cerevisiae
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • ras GTPase-Activating Proteins
  • Cyclic AMP
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • Adenylyl Cyclases