Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

APP (P05067) - Overview - Molecular Target Synopsis


APP, Amyloid-beta precursor protein
UniProt P05067

Also Known as A4_HUMAN, APP, A4, AD1

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). Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. Amyloid-beta associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu(2+) ions (PubMed:25122912). Can form homodimers; this is promoted by heparin binding. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Interacts with SORL1. Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (PubMed:11689470). Interacts with SYT7.

Inspect Structure
See all 3D Structures for APP

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

Gene Copy Number Variation

In COSMIC - Cell Lines Project APP has gain in 1 cell-lines, loss in 3 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: T47D, HS578T, CAKI_1

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: GTL-16, NCI-H1781, G120

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HMEC, HSMM

(see details)

3D Structures

For APP there are:
140 structures (386 chains) solved
11 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

APP has been screened with 1917 compounds (3260 bioactivities), 377 compounds have bioactivities that show binding affinity of <= 500nM (431 bioactivities). (see details)