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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. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; Cell surface; Membrane protein, integral; Receptor, misc.; Transcription factor
Chromosomal Location of Human Ortholog: 21q21.3
Cellular Component: apical part of cell; axon; cell surface; ciliary rootlet; clathrin-coated pit; COPII-coated ER to Golgi transport vesicle; cytoplasm; cytosol; dendritic shaft; dendritic spine; endoplasmic reticulum lumen; endosome; extracellular exosome; extracellular region; extracellular space; Golgi apparatus; Golgi lumen; integral component of membrane; integral component of plasma membrane; intercellular junction; main axon; membrane raft; neuromuscular junction; nuclear envelope lumen; perinuclear region of cytoplasm; plasma membrane; receptor complex; rough endoplasmic reticulum; smooth endoplasmic reticulum; spindle midzone; synapse; terminal bouton; trans-Golgi network membrane
Molecular Function: DNA binding; enzyme binding; heparin binding; identical protein binding; protease activator activity; protein binding; PTB domain binding; receptor binding; serine-type endopeptidase inhibitor activity; transition metal ion binding
Biological Process: adult locomotory behavior; amyloid fibril formation; astrocyte activation; astrocyte activation during immune response; axon cargo transport; axon midline choice point recognition; axonogenesis; cell adhesion; cellular copper ion homeostasis; cellular process; cellular protein metabolic process; cellular response to amyloid-beta; cellular response to cAMP; cellular response to norepinephrine stimulus; cholesterol metabolic process; collateral sprouting in the absence of injury; dendrite development; endocytosis; extracellular matrix organization; forebrain development; G-protein coupled receptor signaling pathway; innate immune response; ionotropic glutamate receptor signaling pathway; learning; learning and/or memory; locomotory behavior; mating behavior; microglia development; modulation of excitatory postsynaptic potential; mRNA polyadenylation; negative regulation of cell proliferation; negative regulation of endopeptidase activity; negative regulation of gene expression; negative regulation of long-term synaptic potentiation; negative regulation of low-density lipoprotein receptor activity; negative regulation of neuron differentiation; neuromuscular process controlling balance; neuron apoptosis; neuron projection development; neuron remodeling; Notch signaling pathway; platelet degranulation; positive regulation of amyloid fibril formation; positive regulation of amyloid-beta formation; positive regulation of astrocyte activation; positive regulation of ERK1 and ERK2 cascade; positive regulation of G2/M transition of mitotic cell cycle; positive regulation of gene expression; positive regulation of JNK cascade; positive regulation of long-term synaptic potentiation; positive regulation of microglial cell activation; positive regulation of mitotic cell cycle; positive regulation of NF-kappaB import into nucleus; positive regulation of NF-kappaB transcription factor activity; positive regulation of NIK/NF-kappaB signaling; positive regulation of peptidase activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of protein binding; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of T cell migration; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; post-translational protein modification; protein amino acid phosphorylation; regulation of epidermal growth factor receptor activity; regulation of long-term neuronal synaptic plasticity; regulation of multicellular organism growth; regulation of NMDA receptor activity; regulation of synapse structure or activity; regulation of translation; response to lead ion; response to oxidative stress; smooth endoplasmic reticulum calcium ion homeostasis; suckling behavior; synapse organization; synaptic growth at neuromuscular junction; tumor necrosis factor production; visual learning
Disease: Alzheimer Disease
Reference #:  P05067 (UniProtKB)
Alt. Names/Synonyms: A4; AAA; ABETA; ABPP; AD1; AICD-50; AICD-57; AICD-59; AID(50); AID(57); AID(59); Alzheimer disease amyloid protein; amyloid beta (A4) precursor protein; Amyloid beta A4 protein; Amyloid intracellular domain 50; Amyloid intracellular domain 57; Amyloid intracellular domain 59; APP; APPI; beta-amyloid peptide; Beta-amyloid protein 40; Beta-amyloid protein 42; Beta-APP40; Beta-APP42; C31; C80; C83; C99; Cerebral vascular amyloid peptide; CTFgamma; CVAP; Gamma-CTF(50); Gamma-CTF(57); Gamma-CTF(59); Gamma-secretase C-terminal fragment 50; Gamma-secretase C-terminal fragment 57; Gamma-secretase C-terminal fragment 59; N-APP; P3(40); P3(42); peptidase nexin-II; PN-II; PN2; PreA4; Protease nexin-II; S-APP-alpha; S-APP-beta; Soluble APP-alpha; Soluble APP-beta
Gene Symbols: APP
Molecular weight: 86,943 Da
Basal Isoelectric point: 4.73  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  Apoptosis Regulation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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