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Neurofibromatosis Type 1 pp 305–326Cite as

Neurofibromin: Protein Domains and Functional Characteristics

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Abstract

The tumor suppressor gene NF1 encodes the giant signal regulator neurofibromin (320 kDa) that is nonfunctional in NF1 patients due to gene alterations. Neurofibromin is a Ras-specific GTPase activating protein (RasGAP) which downregulates the biological activity of activated Ras via a central GAP-related domain (GRD). Adjacent to its carboxy terminal end, a bipartite glycerophospholipid binding module has been discovered that comprises a Sec14- and a pleckstrin homology (PH)-like domain. While a number of interaction partners of neurofibromin have been reported, the RasGAP activity currently appears to represent the only clearly defined biochemical function of this giant protein. This chapter is focused on current knowledge about neurofibromin domains that are structurally validated. Functional and regulatory features will be briefly addressed and the potential impact of non-truncating NF1 mutations detected in patients will be discussed in the light of available three-dimensional structural information.

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Acknowledgements

We thank our colleagues for sharing views and discussions and apologize for not being able to give a comprehensive bibliography owing to space limitations. Work in our laboratory has been supported by grants from the US Department of Defense, the German Federal Ministry of Education and Research, the Baden-Württemberg Foundation (Germany) and the Peter and Traudl Engelhorn Stiftung (Penzberg, Germany).

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  1. Division of Biological Chemistry, Innsbruck Medical University—Biocenter, Innrain 80, 6020, Innsbruck, Austria

    Klaus Scheffzek & Stefan Welti

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  1. Klaus Scheffzek
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  2. Stefan Welti
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Correspondence to Klaus Scheffzek .

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  1. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park Campus, Cardiff, 144XN, United Kingdom

    Meena Upadhyaya

  2. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom

    David N. Cooper

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Scheffzek, K., Welti, S. (2012). Neurofibromin: Protein Domains and Functional Characteristics. In: Upadhyaya, M., Cooper, D. (eds) Neurofibromatosis Type 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32864-0_20

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