YFG Logo
APP - amyloid beta (A4) precursor protein

Entrez Gene Name: amyloid beta (A4) precursor protein
Synonyms: AAA, Abetapp, Abpp, AD1, Adap, Ag, Amyloid betaA4 precursor protein, Amyloid precursor, amyloid-beta-protein, Amyloidogenic glycoprotein, APP, APP isoform 1, APPI, appican, CTFgamma, CVAP, E030013M08RIK, Nexin II, P3, PN-II, PN2, PreA4, PROTEASE NEXIN2

Gene Summary

  • Human (351): This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
  • Rat (54226): activates voltage dependent calcium channels; may induce neuronal apoptosis [RGD, Feb 2006]

Cell Regulation

Regulates:
  • APP
  • IL1B
  • TNF
View all 1001 in IPA
Regulated by:
  • APP
  • PSEN1
  • BACE1
View all 919 in IPA
Binds:
  • APBB1
  • APOE
  • APP
View all 354 in IPA
Role in cell:
  • cell death
  • apoptosis
  • expression in
View all 228 in IPA
Disease:
  • Alzheimer's disease
  • memory deficits
  • neurodegeneration
View all 75 in IPA

Biological Process

activation of innate immune response, adult locomotory behavior, apoptosis, axon cargo transport, axon midline choice point recognition, axonogenesis, blood coagulation, cell adhesion, cell death, cellular copper ion homeostasis, collateral sprouting in absence of injury, dendrite development, endocytosis, extracellular matrix organization, forebrain development, G2 phase of mitotic cell cycle, induction of apoptosis, innate immune response, ionotropic glutamate receptor signaling pathway, locomotory behavior, mating behavior, mRNA polyadenylation, negative regulation of endopeptidase activity, negative regulation of neuron differentiation, negative regulation of peptidase activity, neuromuscular process controlling balance, neuron apoptosis, neuron projection development, neuron remodeling, Notch signaling pathway, platelet activation, platelet degranulation, positive regulation of mitotic cell cycle, positive regulation of peptidase activity, positive regulation of transcription from RNA polymerase II promoter, protein phosphorylation, regulation of epidermal growth factor receptor activity, regulation of gene expression, regulation of multicellular organism growth, regulation of synapse structure and activity, regulation of translation, smooth endoplasmic reticulum calcium ion homeostasis, suckling behavior, synaptic growth at neuromuscular junction, visual learning

Cellular Components

apical part of cell, axon, cell surface, ciliary rootlet, coated pit, cytoplasm, cytoplasmic vesicle, cytosol, dendritic shaft, dendritic spine, extracellular region, Golgi apparatus, integral to membrane, integral to plasma membrane, intracellular membrane-bounded organelle, membrane, membrane fraction, neuromuscular junction, neuron projection, perinuclear region of cytoplasm, plasma membrane, platelet alpha granule lumen, spindle midzone, synapse, synaptosome

Literature References

  • 20817278Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI. Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease.Cell 2010 Sep 17;142(6):857-67
  • 18400162Cirrito JR, Kang JE, Lee J, Stewart FR, Verges DK, Silverio LM, Bu G, Mennerick S, Holtzman DM. Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo.Neuron 2008 Apr 10;58(1):42-51
  • 17554300Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.Nature 2007 06 7;447(7145):661-78
View 18625 categorized literature findings and their references in IPA

Molecular Functions

acetylcholine receptor binding, binding, DNA binding, heparin binding, identical protein binding, metal ion binding, peptidase activator activity, peptidase inhibitor activity, protein binding, PTB domain binding, receptor binding, serine-type endopeptidase inhibitor activity

Protein Domains

alpha-secretase cleavage site, amyloid A4, Amyloid A4 N-terminal heparin-binding, amyloid beta domain, amyloid beta precursor protein intracellular domain, amyloid intracellular domain, antigenic epitope, apoE binding site, basolateral sorting signal, beta-amyloid precursor protein C-terminus, beta-secretase cleavage site, carbohydrate recognition domain, caspase cleavage site, central domain, copper binding domain, Copper-binding of amyloid precursor, CuBD, cysteine rich domain, cytoplasmic domain, cytosolic tail domain, DNA binding, E2 domain, E2 domain of amyloid precursor protein, ectodomain, endocytic signal motif, extracellular domain, Fe65 binding domain, gamma secretase cleavage site, growth factor domain, GYENPTY motif, identical protein binding, intracellular domain, kinesin1 binding domain, KPI domain, KU, Kunitz protease inhibitor domain, Kunitz-type domain, Kunitz-type protease inhibitor domain, membrane-proximal domain, NPXY motif, Outer membrane protein (OmpH-like), phosphorylation site, phosphotyrosine binding domain, protease activator, protein binding, PXY motif, receptor binding, serine protease inhibitor, signal peptide, transmembrane domain, YENPTY motif, YxN Motif, zinc binding domain

Subcellular Locations

actin filaments, alpha granules, annulate lamellae, apical compartment, axonal shafts, axons, caveolar membranes, cell periphery, cell surface, cellular membrane, central spindle, centrosome, chromaffin vesicles, ciliary rootlet, clathrin-coated vesicles, Cytoplasm, cytoplasmic vesicles, cytosol, dendrites, dendritic shafts, dendritic spines, detergent insoluble microdomains, detergent-insoluble fractions, detergent-insoluble membrane fraction, detergent-soluble fraction, detergent-soluble membrane fractions, early endosomal fractions, early endosomes, endoplasmic reticulum, endoplasmic reticulum fraction, endosomes, extracellular matrix, Extracellular Space, filopodia, glial limiting membrane, Golgi apparatus, Golgi-enriched fraction, golgi/trans-golgi network-rich vesicle fraction, granular components, growth cone, intracellular membrane-bounded organelle, intracellular space, lamellipodia, late endosomes, low-density microsomal fraction, lysosome, membrane fraction, membrane rafts, microtubules, mitochondria, multivesicular bodies, nerve ending, neurites, neuromuscular junctions, Nucleus, perikaryon, perinuclear region, peripheral lamellae, plasma, Plasma Membrane, plasma membrane fraction, raft fractions, secretory vesicles, soluble fraction, synapse, synaptic plasma membrane fractions, synaptic vesicles, synaptosomal membrane fractions, synaptosomes, trans Golgi network, vesicles