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 Human Ortholog: 21q21.3
Cellular Component:  apical part of cell; astrocyte projection; axon; cell surface; cell-cell junction; ciliary rootlet; clathrin-coated pit; COPII-coated ER to Golgi transport vesicle; cytoplasm; cytosol; dendritic shaft; dendritic spine; early endosome; endoplasmic reticulum lumen; endosome; endosome lumen; extracellular region; extracellular space; Golgi apparatus; Golgi lumen; Golgi-associated vesicle; growth cone filopodium; growth cone lamellipodium; integral component of membrane; integral component of plasma membrane; main axon; membrane raft; neuromuscular junction; nuclear envelope lumen; perikaryon; perinuclear region of cytoplasm; plasma membrane; platelet alpha granule lumen; presynaptic active zone; receptor complex; recycling endosome; rough endoplasmic reticulum; smooth endoplasmic reticulum; spindle midzone; synapse; synaptic vesicle; trans-Golgi network membrane
Molecular Function:  DNA binding; enzyme binding; growth factor receptor binding; heparin binding; identical protein binding; peptidase activator activity; protein binding; PTB domain binding; receptor activator activity; serine-type endopeptidase inhibitor activity; signaling receptor binding; transition metal ion binding
Biological Process:  adult locomotory behavior; amyloid fibril formation; astrocyte activation; astrocyte activation involved in immune response; axo-dendritic 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 copper ion; cellular response to manganese ion; cellular response to nerve growth factor stimulus; cellular response to norepinephrine stimulus; cholesterol metabolic process; cognition; collateral sprouting in 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 or memory; locomotory behavior; mating behavior; microglia development; modulation of age-related behavioral decline; 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 neuron differentiation; neuromuscular process controlling balance; neuron apoptotic process; neuron projection development; neuron projection maintenance; 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 chemokine biosynthetic process; positive regulation of DNA-binding transcription factor activity; 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 interleukin-1 beta biosynthetic process; positive regulation of interleukin-6 biosynthetic process; 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 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 phosphorylation; positive regulation of protein binding; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of signaling receptor activity; positive regulation of T cell migration; positive regulation of transcription by RNA polymerase II; positive regulation of tumor necrosis factor biosynthetic process; post-translational protein modification; protein phosphorylation; regulation of epidermal growth factor-activated receptor activity; regulation of gene expression; regulation of long-term neuronal synaptic plasticity; regulation of multicellular organism growth; regulation of NMDA receptor activity; regulation of peptidyl-tyrosine phosphorylation; regulation of presynapse assembly; regulation of spontaneous synaptic transmission; regulation of synapse structure or activity; regulation of translation; regulation of Wnt signaling pathway; response to interleukin-1; 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; Abeta40; Abeta42; ABPP; AD1; AICD-50; AICD-57; AICD-59; AID(50); AID(57); AID(59); Alpha-CTF; Alpha-secretase C-terminal fragment; Alzheimer disease amyloid protein; Amyloid beta; amyloid beta (A4) precursor protein; Amyloid beta A4 protein; amyloid beta precursor protein; Amyloid intracellular domain 50; Amyloid intracellular domain 57; Amyloid intracellular domain 59; Amyloid precursor protein; Amyloid-beta A4 protein; Amyloid-beta precursor protein; Amyloid-beta protein 40; Amyloid-beta protein 42; APP; APPI; Beta Amyloid; beta-amyloid peptide; beta-amyloid peptide(1-40); beta-amyloid peptide(1-42); beta-amyloid precursor protein; Beta-amyloid protein 40; Beta-amyloid protein 42; Beta-APP40; Beta-APP42; Beta-CTF; Beta-secretase C-terminal fragment; 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; testicular tissue protein Li 2
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, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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