APP - Amyloid beta A4 protein - human protein (Function)
 
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APP »  Amyloid beta A4 protein
 
Protein also known as:  Alzheimer disease amyloid protein. 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
extend overview
1 1873 11
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.  
1
  • UniProtKB
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.  
1
  • UniProtKB
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).  
1
  • UniProtKB
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.  
1
  • UniProtKB
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.  
1
  • UniProtKB
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
  • UniProtKB
DNA bindingdefinition[GO:0003677]  
1
  • Ortholog Curator
Enzyme bindingdefinition[GO:0019899]  
1
  • ParkinsonsUK-UCL
Growth factor receptor bindingdefinition[GO:0070851] silver  
1
  • Ortholog Compara
Heparin bindingdefinition[GO:0008201]  
1
  • UniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
22
  • IntAct
Peptidase activator activitydefinition[GO:0016504] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
57
  • IntAct
  • UniProtKB
  • BHF-UCL
  • Alzheimers_University_of_Toronto
PTB domain bindingdefinition[GO:0051425]  
1
  • BHF-UCL
Receptor bindingdefinition[GO:0005102]  
1
  • BHF-UCL
Serine-type endopeptidase inhibitor activitydefinition[GO:0004867]  
1
  • UniProtKB
Transition metal ion bindingdefinition[GO:0046914] silver  
1
  • InterPro 2 GO
GO biological process 
Adult locomotory behaviordefinition[GO:0008344]  
1
  • Ortholog Curator
Axon cargo transportdefinition[GO:0008088]  
1
  • Ortholog Curator
Axon midline choice point recognitiondefinition[GO:0016199]  
1
  • Ortholog Curator
Axonogenesisdefinition[GO:0007409]  
1
  • Ortholog Curator
Cell adhesiondefinition[GO:0007155]  
1
  • UniProtKB KW
Cellular copper ion homeostasisdefinition[GO:0006878]  
1
  • Ortholog Curator
Cholesterol metabolic processdefinition[GO:0008203] silver  
1
  • Ortholog Compara
Collateral sprouting in absence of injurydefinition[GO:0048669]  
1
  • Ortholog Curator
Dendrite developmentdefinition[GO:0016358]  
1
  • Ortholog Curator
Endocytosisdefinition[GO:0006897]  
1
  • Ortholog Curator
Extracellular matrix organizationdefinition[GO:0030198]  
1
  • Ortholog Curator
Forebrain developmentdefinition[GO:0030900] silver  
1
  • Ortholog Compara
Ionotropic glutamate receptor signaling pathwaydefinition[GO:0035235]  
1
  • Ortholog Curator
Locomotory behaviordefinition[GO:0007626]  
1
  • Ortholog Curator
Mating behaviordefinition[GO:0007617]  
1
  • Ortholog Curator
mRNA polyadenylationdefinition[GO:0006378]  
1
  • Ortholog Curator
Negative regulation of endopeptidase activitydefinition[GO:0010951]  
3
  • GOC
  • InterPro 2 GO
  • UniProtKB KW
Negative regulation of neuron differentiationdefinition[GO:0045665] silver  
1
  • Ortholog Compara
Neuromuscular process controlling balancedefinition[GO:0050885] silver  
1
  • Ortholog Compara
Neuron apoptotic processdefinition[GO:0051402]  
1
  • UniProtKB
Neuron projection developmentdefinition[GO:0031175]  
1
  • Ortholog Curator
Neuron remodelingdefinition[GO:0016322]  
1
  • Ortholog Curator
Notch signaling pathwaydefinition[GO:0007219]  
1
  • UniProtKB KW
Positive regulation of G2/M transition of mitotic cell cycledefinition[GO:0010971] silver  
1
  • Ortholog Compara
Positive regulation of mitotic cell cycledefinition[GO:0045931]  
1
  • Ortholog Curator
Positive regulation of peptidase activitydefinition[GO:0010952] silver  
1
  • Ortholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
1
  • Ortholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • Ortholog Curator
Regulation of epidermal growth factor-activated receptor activitydefinition[GO:0007176]  
1
  • Ortholog Curator
Regulation of multicellular organism growthdefinition[GO:0040014]  
1
  • Ortholog Curator
Regulation of protein bindingdefinition[GO:0043393] silver  
1
  • Ortholog Compara
Regulation of synapse structure or activitydefinition[GO:0050803]  
1
  • Ortholog Curator
Regulation of translationdefinition[GO:0006417]  
1
  • Ortholog Curator
Response to oxidative stressdefinition[GO:0006979] silver  
1
  • Ortholog Compara
Smooth endoplasmic reticulum calcium ion homeostasisdefinition[GO:0051563] silver  
1
  • Ortholog Compara
Suckling behaviordefinition[GO:0001967] silver  
1
  • Ortholog Compara
Synaptic growth at neuromuscular junctiondefinition[GO:0051124] silver  
1
  • Ortholog Compara
Visual learningdefinition[GO:0008542]  
1
  • Ortholog 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:
Advanced glycosylation endproduct receptor signaling  REACT_25195  
Amyloids  REACT_75925  
ECM proteoglycans  REACT_163906  
Formyl peptide receptors bind formyl peptides and many other ligands  REACT_21264  
G alpha (i) signalling events  REACT_19231  
G alpha (q) signalling events  REACT_18283  
RIP-mediated NFkB activation via ZBP1  REACT_118563  
TAK1 activates NFkB by phosphorylation and activation of IKKs complex  REACT_21281  
The NLRP3 inflammasome  REACT_75808  
TRAF6 mediated NF-kB activation  REACT_24969  
 
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