Tclin APP Amyloid-beta A4 protein

Protein Summary

Description

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). 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. Amyloid-beta 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. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). 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. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. 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, Aug 2014]

Uniprot Accession IDs

• P05067
• B2R5V1
• B4DII8
• D3DSD1
• D3DSD2
• D3DSD3
• P09000
• P78438
• Q13764
• Q13778
• Q13793
• Q16011
• Q16014
• Q16019
• Q16020
• Q6GSC0
• Q8WZ99
• Q9BT38
• Q9UC33
• Q9UCA9
• Q9UCB6
• Q9UCC8
• Q9UCD1
• Q9UQ58

Gene Name

• APP

Ensembl ID

• ENST00000346798
• ENSP00000284981
• ENSG00000142192
• ENST00000348990
• ENSP00000345463
• ENST00000354192
• ENSP00000346129
• ENST00000357903
• ENSP00000350578
• ENST00000358918
• ENSP00000351796
• ENST00000440126
• ENSP00000387483

Symbol

• A4
• AD1
• AAA
• AD1
• PN2
• ABPP
• APPI
• CVAP
• ABETA
• PN-II
• preA4
• CTFgamma

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
disease perturbation	1
hub protein	1

Protein Classes

PANTHER Classes

Protein / ... / Protease Inhibitor / Amyloid-beta A4 Protein

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Amyloid-beta A4 Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 14947.46   (req: < 5)

Gene RIFs: 2554   (req: <= 3)

Antibodies: 3786   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 14947.46   (req: >= 5)

Gene RIFs: 2554   (req: > 3)

Antibodies: 3786   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 170

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 727

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4