Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization.
The Notch signaling pathway plays a role in cell fate specification in many metazoans. A critical aspect of Notch activation involves proteolysis of the Notch receptor. This cleavage event requires Presenilin as a component of a large multiprotein complex, gamma-secretase. This complex mediates a similar cleavage event of the beta-amyloid precursor protein (APP). The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent biochemical and genetic studies have focused on elucidating the function of this protein.
Kopan
Raphael
R
Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. kopan@pcg.wustl.edu
Goate
Alison
A
D000544:Alzheimer Disease / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000502:physiology; D010450:Endopeptidases / Q000378:metabolism*; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D053764:Presenilin-1; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; C508853:PSEN1 protein, human; D053764:Presenilin-1; D051880:Receptors, Notch; D015534:Trans-Activators; C410543:aph-2 protein, C elegans; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human