APP (Beta Amyloid Precursor) is a protein that functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. It is involved in cell mobility and transcription regulation through protein-protein interactions and can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. It couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP and also inhibits G(o) alpha ATPase activity. It functions as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. It is also involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation. It can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. APP induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons.
References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804