APP - Amyloid beta A4 protein - human protein (Function)
 
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APP »  Amyloid beta A4 protein
 
Protein also known as:  Cerebral vascular amyloid peptide (CVAP). Cleaved into:  Beta-amyloid protein 40; Beta-amyloid protein 42; C31; C80; C83; C99; Gamma-secretase C-terminal fragment 50; Gamma-secretase C-terminal fragment 57; Gamma-secretase C-terminal fragment 59; N-APP; P3(40); P3(42); Soluble APP-alpha; Soluble APP-beta.
Gene name:  APP
Family name: APP
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 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 (By similarity). 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. 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 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.  
5
  • CuratedUniProtKB
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).  
5
  • CuratedUniProtKB
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.  
5
  • CuratedUniProtKB
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).  
5
  • CuratedUniProtKB
Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.  
5
  • CuratedUniProtKB
According to TCDB this is a transporter from family:
the amyloid -protein peptide (app) family  1.C.50.1.2  
GO molecular function 
Acetylcholine receptor bindingdefinition[GO:0033130]  
1
  • IPIUniProtKB
DNA bindingdefinition[GO:0003677]  
  • ISSOrtholog Curator
Growth factor receptor bindingdefinition[GO:0070851] silver  
  • IEAOrtholog Compara
Heparin bindingdefinition[GO:0008201]  
  • IEAUniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
20
  • IPIIntAct
Peptidase activator activitydefinition[GO:0016504] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
52
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
PTB domain bindingdefinition[GO:0051425]  
1
  • IPIBHF-UCL
Receptor bindingdefinition[GO:0005102]  
1
  • IPIBHF-UCL
Serine-type endopeptidase inhibitor activitydefinition[GO:0004867]  
1
  • IDAUniProtKB
Transition metal ion bindingdefinition[GO:0046914] silver  
  • IEAInterPro 2 GO
GO biological process 
Adult locomotory behaviordefinition[GO:0008344]  
  • ISSOrtholog Curator
Axon cargo transportdefinition[GO:0008088]  
  • ISSOrtholog Curator
Axon midline choice point recognitiondefinition[GO:0016199]  
  • ISSOrtholog Curator
Axonogenesisdefinition[GO:0007409]  
  • ISSOrtholog Curator
Cell adhesiondefinition[GO:0007155]  
  • IEAUniProtKB KW
Cellular copper ion homeostasisdefinition[GO:0006878]  
  • ISSOrtholog Curator
Cholesterol metabolic processdefinition[GO:0008203] silver  
  • IEAOrtholog Compara
Collateral sprouting in absence of injurydefinition[GO:0048669]  
  • ISSOrtholog Curator
Dendrite developmentdefinition[GO:0016358]  
  • ISSOrtholog Curator
Endocytosisdefinition[GO:0006897]  
  • ISSOrtholog Curator
Extracellular matrix organizationdefinition[GO:0030198]  
  • ISSOrtholog Curator
Forebrain developmentdefinition[GO:0030900] silver  
  • IEAOrtholog Compara
Ionotropic glutamate receptor signaling pathwaydefinition[GO:0035235]  
  • ISSOrtholog Curator
Locomotory behaviordefinition[GO:0007626]  
  • ISSOrtholog Curator
Mating behaviordefinition[GO:0007617]  
  • ISSOrtholog Curator
Mitotic G2 phasedefinition[GO:0000085]  
  • ISSOrtholog Curator
mRNA polyadenylationdefinition[GO:0006378]  
  • ISSOrtholog Curator
Negative regulation of endopeptidase activitydefinition[GO:0010951]  
1
  • IDAGOC
Negative regulation of neuron differentiationdefinition[GO:0045665] silver  
  • IEAOrtholog Compara
Neuromuscular process controlling balancedefinition[GO:0050885] silver  
  • IEAOrtholog Compara
Neuron apoptotic processdefinition[GO:0051402]  
1
  • IMPUniProtKB
Neuron projection developmentdefinition[GO:0031175]  
  • ISSOrtholog Curator
Neuron remodelingdefinition[GO:0016322]  
  • ISSOrtholog Curator
Notch signaling pathwaydefinition[GO:0007219]  
  • IEAUniProtKB KW
Positive regulation of G2/M transition of mitotic cell cycledefinition[GO:0010971] silver  
  • IEAOrtholog Compara
Positive regulation of mitotic cell cycledefinition[GO:0045931]  
  • ISSOrtholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
  • ISSOrtholog Curator
Regulation of endopeptidase activitydefinition[GO:0052548]  
1
  • IDAGOC
Regulation of epidermal growth factor-activated receptor activitydefinition[GO:0007176]  
  • ISSOrtholog Curator
Regulation of multicellular organism growthdefinition[GO:0040014]  
  • ISSOrtholog Curator
Regulation of protein bindingdefinition[GO:0043393] silver  
  • IEAOrtholog Compara
Regulation of synapse structure and activitydefinition[GO:0050803]  
  • ISSOrtholog Curator
Regulation of translationdefinition[GO:0006417]  
  • ISSOrtholog Curator
Response to oxidative stressdefinition[GO:0006979] silver  
  • IEAOrtholog Compara
Smooth endoplasmic reticulum calcium ion homeostasisdefinition[GO:0051563] silver  
  • IEAOrtholog Compara
Suckling behaviordefinition[GO:0001967] silver  
  • IEAOrtholog Compara
Synaptic growth at neuromuscular junctiondefinition[GO:0051124] silver  
  • IEAOrtholog Compara
Visual learningdefinition[GO:0008542]  
  • ISSOrtholog Curator
Enzymatic activity 
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathway:
Alzheimer's disease  hsa05010+351  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Extracellular matrix organization  REACT_118779  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 
More information is available from:
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell adhesion  definition   [KW-0130]
Endocytosis  definition   [KW-0254]
Notch signaling pathway  definition   [KW-0914]
Molecular function 
Protease inhibitor  definition   [KW-0646]
Serine protease inhibitor  definition   [KW-0722]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P05067
Other
GeneWiki: Amyloid_precursor_protein
GenomeRNAi: 351
PRO: PR:P05067