| Tissue Specificity | Expressed in the brain. In the brain, non-L-APP isoforms are expressed in neurons, isoform APP695 being the predominant form. In astrocytes and microglial cells, almost 50% is L-isoform (appican). |
| Post Translational Modifications | Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE. Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase. Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-3, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides. N-glycosylated. O-glycosylated. O-linkage of chondroitin sulfate to the L-APP isoforms produces the APP proteoglycan core proteins, the appicans. The chondroitin sulfate chain of appicans contains 4-O-sulfated galactose in the linkage region and chondroitin sulfate E in the repeated disaccharide region. Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin. Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). Amyloid-beta peptides are degraded by IDE. Sulfated on tyrosine residues. |
| Function | 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. 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. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons. 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. 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 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. Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse amyloid-beta peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Amyloid-beta protein 42 may activate mononuclear phagocytes in the brain and elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also binds GPC1 in lipid rafts. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. |
| Protein Name | Amyloid-Beta Precursor ProteinAbppAppAlzheimer Disease Amyloid A4 Protein HomologAlzheimer Disease Amyloid ProteinAmyloid Precursor ProteinAmyloid-BetaA4 Precursor ProteinAmyloid-Beta A4 ProteinAmyloidogenic GlycoproteinAg Cleaved Into - N-App - Soluble App-AlphaS-App-Alpha - Soluble App-BetaS-App-Beta - C99Beta-Secretase C-Terminal FragmentBeta-Ctf - Amyloid-Beta Protein 42Abeta42Beta-App42 - Amyloid-Beta Protein 40Abeta40Beta-App40 - C83Alpha-Secretase C-Terminal FragmentAlpha-Ctf - P3(42 - P3(40 - C80 - Gamma-Secretase C-Terminal Fragment 59Gamma-Ctf(59 - Gamma-Secretase C-Terminal Fragment 57Gamma-Ctf(57 - Gamma-Secretase C-Terminal Fragment 50Gamma-Ctf(50 - C31 |
| Database Links | Reactome: R-RNO-114608Reactome: -RNO-3000178Reactome: -RNO-381426Reactome: -RNO-416476Reactome: -RNO-418594Reactome: -RNO-432720Reactome: -RNO-444473Reactome: -RNO-445989Reactome: -RNO-879415Reactome: -RNO-8957275Reactome: -RNO-933542Reactome: -RNO-9609523Reactome: -RNO-9837999 |
| Cellular Localisation | Cell MembraneSingle-Pass Type I Membrane ProteinMembranePerikaryonCell ProjectionGrowth ConeClathrin-Coated PitEarly EndosomeCytoplasmic VesicleCell Surface Protein That Rapidly Becomes Internalized Via Clathrin-Coated PitsOnly A Minor Proportion Is Present At The Cell MembraneMost Of The Protein Is Present In Intracellular VesiclesDuring MaturationThe Immature App (N-Glycosylated In The Endoplasmic Reticulum) Moves To The Golgi Complex Where Complete Maturation Occurs (O-Glycosylated And Sulfated)After Alpha-Secretase CleavageSoluble App Is Released Into The Extracellular Space And The C-Terminal Is Internalized To Endosomes And LysosomesSome App Accumulates In Secretory Transport Vesicles Leaving The Late Golgi Compartment And Returns To The Cell SurfaceApp Sorts To The Basolateral Surface In Epithelial CellsDuring Neuronal DifferentiationThe Thr-742 Phosphorylated Form Is Located Mainly In Growth ConesModerately In Neurites And Sparingly In The Cell BodyCasein Kinase Phosphorylation Can Occur Either At The Cell Surface Or Within A Post-Golgi CompartmentAssociates With Gpc1 In Perinuclear CompartmentsColocalizes With Sorl1 In A Vesicular Pattern In Cytoplasm And Perinuclear RegionsC83: Endoplasmic ReticulumGolgi ApparatusC99: Early EndosomeAmyloid-Beta Protein 42: Cell SurfaceAssociates With Fpr2 At The Cell Surface And The Complex Is Then Rapidly InternalizedGamma-Secretase C-Terminal Fragment 59: NucleusCytoplasmLocated To Both The Cytoplasm And Nuclei Of NeuronsIt Can Be Translocated To The Nucleus Through Association With Apbb1 (Fe65)In Dopaminergic NeuronsThe Phosphorylated Thr-743 Form Is Localized To The NucleusSoluble App-Beta: Secreted |
| Alternative Antibody Names | Anti-Amyloid-Beta Precursor Protein antibodyAnti-Abpp antibodyAnti-App antibodyAnti-Alzheimer Disease Amyloid A4 Protein Homolog antibodyAnti-Alzheimer Disease Amyloid Protein antibodyAnti-Amyloid Precursor Protein antibodyAnti-Amyloid-Beta antibodyAnti-A4 Precursor Protein antibodyAnti-Amyloid-Beta A4 Protein antibodyAnti-Amyloidogenic Glycoprotein antibodyAnti-Ag Cleaved Into - N-App - Soluble App-Alpha antibodyAnti-S-App-Alpha - Soluble App-Beta antibodyAnti-S-App-Beta - C99 antibodyAnti-Beta-Secretase C-Terminal Fragment antibodyAnti-Beta-Ctf - Amyloid-Beta Protein 42 antibodyAnti-Abeta42 antibodyAnti-Beta-App42 - Amyloid-Beta Protein 40 antibodyAnti-Abeta40 antibodyAnti-Beta-App40 - C83 antibodyAnti-Alpha-Secretase C-Terminal Fragment antibodyAnti-Alpha-Ctf - P3(42 - P3(40 - C80 - Gamma-Secretase C-Terminal Fragment 59 antibodyAnti-Gamma-Ctf(59 - Gamma-Secretase C-Terminal Fragment 57 antibodyAnti-Gamma-Ctf(57 - Gamma-Secretase C-Terminal Fragment 50 antibodyAnti-Gamma-Ctf(50 - C31 antibodyAnti-App antibodyAnti-A4 antibodyAnti-AD1 antibody |
