APP: a cell surface receptor that influences neurite growth, neuronal adhesion and axonogenesis. Cleaved by secretases to form a number of peptides, some of which bind to the acetyltransferase complex Fe65/TIP60 to promote transcriptional activation. The Abeta peptide is released from the cell, its extracellular deposition and accumulation form the main components of amyloid plaques in Alzheimer's disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis. Can promote transcription activation through binding to Fe65-Tip60 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. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. 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. Induces a RAGE-dependent pathway that activates 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. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, JIP1, SHC1 and, NUMB and DAB1. Binding to DAB1 inhibits its serine phosphorylation. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner. Amyloid beta-42 binds nAChRA7 in hippocampal neurons. Beta-amyloid associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex- opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra- striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. 10 isoforms of the human protein are produced by alternative splicing. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non- neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Belongs to the APP family.

Protein type: Receptor, misc.; Transcription factor; Membrane protein, integral; Apoptosis; Cell surface

Cellular Component: Golgi apparatus; extracellular space; neuron projection; cell surface; smooth endoplasmic reticulum; intracellular membrane-bound organelle; cell; dendritic spine; integral to membrane; terminal button; coated pit; intercellular junction; ER to Golgi transport vesicle; lipid raft; ciliary rootlet; synaptic vesicle; membrane; apical part of cell; axon; perinuclear region of cytoplasm; nuclear envelope lumen; cytoplasm; plasma membrane; synapse; cytoplasmic vesicle; dendritic shaft; intracellular; spindle midzone; neuromuscular junction; receptor complex; endosome

Molecular Function: heparin binding; serine-type endopeptidase inhibitor activity; identical protein binding; protein binding; protease activator activity; enzyme binding; DNA binding; transition metal ion binding; PTB domain binding; acetylcholine receptor binding; receptor binding

Biological Process: extracellular matrix organization and biogenesis; adult locomotory behavior; mRNA polyadenylation; locomotory behavior; positive regulation of mitotic cell cycle; protein amino acid phosphorylation; regulation of translation; synaptic growth at neuromuscular junction; forebrain development; dendrite development; collateral sprouting in the absence of injury; visual learning; cell adhesion; neuromuscular process controlling balance; neurite development; cholesterol metabolic process; Notch signaling pathway; cellular copper ion homeostasis; regulation of epidermal growth factor receptor activity; axon cargo transport; mating behavior; regulation of multicellular organism growth; endocytosis; axon midline choice point recognition; smooth endoplasmic reticulum calcium ion homeostasis; neuron apoptosis; negative regulation of neuron differentiation; axonogenesis; suckling behavior; ionotropic glutamate receptor signaling pathway; regulation of gene expression; regulation of protein binding; regulation of synapse structure and activity; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; neuron remodeling

Disease: Alzheimer Disease