APP a single-pass type I membrane protein expressed in many tissues and concentrated in neurons, where it influences neurite growth, neuronal adhesion, axonogenesis and iron export. A lipophilic metal chelator with metal-reducing activity. Involved in copper homeostasis/oxidative stress through copper ion reduction. Mutations are linked to autosomal dominant Alzheimer disease and cerebroarterial amyloidosis. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Proteolysis by beta-secretase (BACE1) and gamma-secretase releases C-terminal Abeta40/42 peptides predominantly into the extracellular space, and the APP Intracellular C-terminal Domain (AICD) peptide into the cytoplasm where it translocates to the nucleus. The Abeta peptides form the main component of amyloid plaques in the brains of Alzheimer's disease patients. The AICD peptide forms a transcriptionally active ternary complex with APBB1 and the histone acetyltransferase Tip60, modulating gene expression, apoptosis, cytoskeletal dynamics, and mitochondrial distribution and morphology. Binds to the PID domain of several cytoplasmic proteins, including APBA & -B family members, JIP1, SHC1, NUMB and DAB1. Inhibits Notch signaling through interaction with Numb. Binding to DAB1 inhibits its serine phosphorylation. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner. 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. 11 isoforms of the human protein are produced by alternative splicing. Isoform APP695 (P05067-4) is the predominant form in neuronal tissue, isoform APP751 (P05067-8) and isoform APP770 (P05067-1) are widely expressed in non- neuronal cells. Isoform APP751 (P05067-8) is the most abundant form in T-lymphocytes. Appican (isoforms P05067-3/-5/-7) is expressed in astrocytes and may stimulate of both neural cell adhesion and neurite outgrowth. The splice isoforms that contain the Kunitz-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 rat Ortholog: 11q11
Cellular Component:  amyloid-beta complex; apical part of cell; astrocyte projection; axon; cell body; cell surface; cell-cell junction; ciliary rootlet; clathrin-coated pit; COPII-coated ER to Golgi transport vesicle; cytoplasm; cytoplasmic vesicle; dendrite; dendrite membrane; dendritic shaft; dendritic spine; early endosome; endoplasmic reticulum; endosome; endosome to plasma membrane transport vesicle; external side of plasma membrane; extracellular space; Golgi apparatus; Golgi-associated vesicle; growth cone; growth cone filopodium; growth cone lamellipodium; high-density lipoprotein particle; intermediate-density lipoprotein particle; lipoprotein particle; low-density lipoprotein particle; lysosome; main axon; membrane; membrane raft; mitochondrion; neuromuscular junction; neuron projection; neuronal dense core vesicle; nuclear envelope lumen; nucleus; perikaryon; perinuclear region of cytoplasm; plasma membrane; postsynapse; presynapse; presynaptic active zone; protein-containing complex; receptor complex; recycling endosome; smooth endoplasmic reticulum; spindle midzone; synapse; synaptic membrane; synaptic vesicle; very-low-density lipoprotein particle
Molecular Function:  acetylcholine receptor binding; apolipoprotein binding; chemoattractant activity; chromatin binding; DNA binding; enzyme binding; ephrin receptor binding; frizzled binding; G protein-coupled receptor binding; growth factor receptor binding; heparan sulfate proteoglycan binding; heparin binding; identical protein binding; insulin receptor binding; integrin binding; ion binding; low-density lipoprotein particle receptor binding; peptidase activator activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein-folding chaperone binding; PTB domain binding; RAGE receptor binding; receptor ligand activity; RNA polymerase II cis-regulatory region sequence-specific DNA binding; serine-type endopeptidase inhibitor activity; signaling receptor activator activity; signaling receptor binding; transition metal ion binding
Biological Process:  adenylate cyclase-activating G protein-coupled receptor signaling pathway; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; adult locomotory behavior; amyloid fibril formation; antibacterial humoral response; antifungal humoral response; antimicrobial humoral immune response mediated by antimicrobial peptide; associative learning; astrocyte activation; astrocyte activation involved in immune response; axo-dendritic transport; axon midline choice point recognition; axonogenesis; calcium-mediated signaling; cell adhesion; cellular response to amyloid-beta; cellular response to cAMP; cellular response to copper ion; cellular response to manganese ion; cellular response to nerve growth factor stimulus; cellular response to norepinephrine stimulus; central nervous system development; chemical synaptic transmission; cholesterol metabolic process; cognition; collateral sprouting in absence of injury; cytoplasmic polyadenylation; defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; dendrite development; endocytosis; extracellular matrix organization; forebrain development; G protein-coupled receptor signaling pathway; G2/M transition of mitotic cell cycle; innate immune response; intracellular copper ion homeostasis; ionotropic glutamate receptor signaling pathway; learning; learning or memory; locomotory behavior; mating behavior; memory; microglia development; microglial cell activation; mitotic cell cycle; modulation of excitatory postsynaptic potential; mRNA polyadenylation; negative regulation of blood circulation; negative regulation of canonical Wnt signaling pathway; negative regulation of cell population proliferation; negative regulation of dendritic spine maintenance; negative regulation of gene expression; negative regulation of long-term synaptic potentiation; negative regulation of low-density lipoprotein receptor activity; negative regulation of miRNA transcription; negative regulation of neuron differentiation; negative regulation of peptidase activity; negative regulation of protein localization to nucleus; negative regulation of transcription by RNA polymerase II; negative regulation of Wnt signaling pathway; neuromuscular process controlling balance; neuron apoptotic process; neuron cellular homeostasis; neuron differentiation; neuron projection development; neuron projection maintenance; neuron remodeling; Notch signaling pathway; positive regulation of amyloid fibril formation; positive regulation of apoptotic process; positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; positive regulation of chemokine production; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of DNA-binding transcription factor activity; positive regulation of endothelin production; positive regulation of ERK1 and ERK2 cascade; positive regulation of excitatory postsynaptic potential; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of G protein-coupled receptor internalization; positive regulation of G protein-coupled receptor signaling pathway; positive regulation of G2/M transition of mitotic cell cycle; positive regulation of gene expression; positive regulation of glycolytic process; positive regulation of histone acetylation; positive regulation of inflammatory response; positive regulation of interleukin-1 beta production; positive regulation of interleukin-6 production; positive regulation of JNK cascade; positive regulation of long-term synaptic depression; positive regulation of long-term synaptic potentiation; positive regulation of MAP kinase activity; positive regulation of MAPK cascade; positive regulation of membrane protein ectodomain proteolysis; positive regulation of mitotic cell cycle; positive regulation of monocyte chemotaxis; positive regulation of neuron apoptotic process; positive regulation of neuron differentiation; positive regulation of NF-kappaB transcription factor activity; positive regulation of NIK/NF-kappaB signaling; positive regulation of nitric oxide biosynthetic process; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphorylation; positive regulation of protein binding; positive regulation of protein import; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of protein tyrosine kinase activity; positive regulation of receptor binding; positive regulation of response to endoplasmic reticulum stress; positive regulation of superoxide anion generation; positive regulation of T cell migration; positive regulation of tau-protein kinase activity; positive regulation of transcription by RNA polymerase II; positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; positive regulation of tumor necrosis factor production; positive regulation of type II interferon production; protein homooligomerization; protein phosphorylation; protein tetramerization; protein trimerization; regulation of acetylcholine-gated cation channel activity; regulation of amyloid fibril formation; regulation of amyloid-beta clearance; regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; regulation of dendritic spine maintenance; regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway; regulation of epidermal growth factor-activated receptor activity; regulation of gene expression; regulation of long-term neuronal synaptic plasticity; regulation of MAPK cascade; regulation of multicellular organism growth; regulation of peptidyl-tyrosine phosphorylation; regulation of presynapse assembly; regulation of protein binding; regulation of protein tyrosine kinase activity; regulation of response to calcium ion; regulation of signaling receptor activity; regulation of spontaneous synaptic transmission; regulation of synapse structure or activity; regulation of toll-like receptor signaling pathway; regulation of transcription by RNA polymerase II; regulation of translation; response to auditory stimulus; response to interleukin-1; response to lead ion; response to oxidative stress; response to yeast; smooth endoplasmic reticulum calcium ion homeostasis; suckling behavior; synapse organization; synaptic assembly at neuromuscular junction; visual learning
Disease: Alzheimer Disease
Reference #:  P08592 (UniProtKB)
Alt. Names/Synonyms: A4; ABPP; AG; Alzheimer disease amyloid A4 protein homolog; amyloid beta (A4) precursor protein; Amyloid beta A4 protein; Amyloid-beta A4 protein; Amyloid-beta precursor protein; Amyloidogenic glycoprotein; APP; Beta Amyloid; Beta-amyloid protein 40; Beta-amyloid protein 42; Beta-APP40; Beta-APP42; C31; C80; C83; C99; 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); S-APP-alpha; S-APP-beta; Soluble APP-alpha; Soluble APP-beta
Gene Symbols: App
Molecular weight: 86,704 Da
Basal Isoelectric point: 4.73  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  Apoptosis Regulation
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene