5myk

Structural highlights

Function

[A4_MOUSE] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. 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 (By similarity). Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.^[1] Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts (By similarity).^[2] The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.^[3] N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (By similarity).^[4]

References

1. ↑ Cappai R, Cheng F, Ciccotosto GD, Needham BE, Masters CL, Multhaup G, Fransson LA, Mani K. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. J Biol Chem. 2005 Apr 8;280(14):13913-20. Epub 2005 Jan 27. PMID:15677459 doi:http://dx.doi.org/10.1074/jbc.M409179200
2. ↑ Cappai R, Cheng F, Ciccotosto GD, Needham BE, Masters CL, Multhaup G, Fransson LA, Mani K. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. J Biol Chem. 2005 Apr 8;280(14):13913-20. Epub 2005 Jan 27. PMID:15677459 doi:http://dx.doi.org/10.1074/jbc.M409179200
3. ↑ Cappai R, Cheng F, Ciccotosto GD, Needham BE, Masters CL, Multhaup G, Fransson LA, Mani K. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. J Biol Chem. 2005 Apr 8;280(14):13913-20. Epub 2005 Jan 27. PMID:15677459 doi:http://dx.doi.org/10.1074/jbc.M409179200
4. ↑ Cappai R, Cheng F, Ciccotosto GD, Needham BE, Masters CL, Multhaup G, Fransson LA, Mani K. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. J Biol Chem. 2005 Apr 8;280(14):13913-20. Epub 2005 Jan 27. PMID:15677459 doi:http://dx.doi.org/10.1074/jbc.M409179200
5. ↑ Piechotta A, Parthier C, Kleinschmidt M, Gnoth K, Pillot T, Lues I, Demuth HU, Schilling S, Rahfeld JU, Stubbs MT. Structural and functional analyses of pyroglutamate-amyloid-beta-specific antibodies as a basis for Alzheimer immunotherapy. J Biol Chem. 2017 Jul 28;292(30):12713-12724. doi: 10.1074/jbc.M117.777839. Epub , 2017 Jun 16. PMID:28623233 doi:http://dx.doi.org/10.1074/jbc.M117.777839