|Description: Amyloid beta A4 protein precursor (APP) (ABPP) (Alzheimer diseaseamyloid protein) (Cerebral vascular amyloid peptide) (CVAP) (Proteasenexin-II) (PN-II) (APPI) (PreA4) [Contains: Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99; Beta-amyloid protein 42(Beta-APP42); Beta-amyloid protein 40 (Beta-APP40); C83; P3(42);P3(40); Gamma-CTF(59) (Gamma-secretase C-terminal fragment 59)(Amyloid intracellular domain 59) (AID(59)) (AICD-59); Gamma-CTF(57)(Gamma-secretase C-terminal fragment 57) (Amyloid intracellular domain57) (AID(57)) (AICD-57); Gamma-CTF(50) (Gamma-secretase C-terminalfragment 50) (Amyloid intracellular domain 50) (AID(50)) (AICD-50);C31].|
Synonyms: A4, AD1
Ensembl ID: ENSG00000142192
UniprotKB/SwissProt: A4_HUMAN (P05067)
Function: 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/Tip60 and inhibit 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. 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 overexpressed HADH2 leads to oxidative stress and neurotoxicity. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity). The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Membrane; Single-pass type I membrane protein. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where comple