Neurofibromin is a protein coded for by the NF1 gene located on chromosome 17 (17q11.2). It is a multifunctional protein and is involved in the regulation of many cellular signaling pathways. In patients with a mutation of the NF1 gene, neurofibromin is defective and results in the clinical syndromes of NF1 and NF2.
The protein is expressed in all cell types and is predominantly a cytoplasmic protein. However, in some cell types, neurofibromin has been found within the nucleus . It predominates in neurons, Schwann cells, oligodendrocytes, astrocytes and leukocytes .
It has a number of regulatory behaviors :
- RAS/MAPK pathway
- mTOR pathway
- adenylate cyclase activity
- interacts with a number of other proteins, e.g. microtubulin, kinesin-1, protein kinase A and C, caveolin and amyloid precursor protein
Its regulatory behavior impacts cell growth and proliferation. It mainly acts by regulating the activity of the RAS-family proteins. The neurofibromin protein belongs to a group of proteins called the Ras GTPase-activating proteins (GAP). Their activity is mediated by accelerating the hydrolysis of GTP bound to active RAS protein.