Human Amyloid-beta precursor protein,APP ELI

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.

Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912).

Involved in cell mobility and transcription regulation through protein-protein interactions.

Can promote transcription activation through binding to APBB1-KAT5 and inhibits 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 (By similarity).

By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729).

Involved in copper homeostasis/oxidative stress through copper ion reduction.

In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation.

Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV.

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.

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.

{ECO:0000250, ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:17062754, ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:25122912}.; Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity.

Bind transient metals such as copper, zinc and iron.

In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively.

Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40.

Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins.

APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses.

Promotes both tau aggregation and TPK II-mediated phosphorylation.

Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity.

Also binds GPC1 in lipid rafts.; Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.

{ECO:0000250}.; The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).