[{"uniprot":["P05067"],"uniprot_sum":[{"prot_name":"Amyloid-beta precursor protein (APP) (ABPP) (APPI) (Alzheimer disease amyloid A4 protein homolog) (Alzheimer disease amyloid protein) (Amyloid precursor protein) (Amyloid-beta (A4) precursor protein) (Amyloid-beta A4 protein) (Cerebral vascular amyloid peptide) (CVAP) (PreA4) (Protease nexin-II) (PN-II) [Cleaved into: N-APP; Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99 (Beta-secretase C-terminal fragment) (Beta-CTF); Amyloid-beta protein 42 (Abeta42) (Beta-APP42); Amyloid-beta protein 40 (Abeta40) (Beta-APP40); C83 (Alpha-secretase C-terminal fragment) (Alpha-CTF); P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59 (Amyloid intracellular domain 59) (AICD-59) (AID(59)) (Gamma-CTF(59)); Gamma-secretase C-terminal fragment 57 (Amyloid intracellular domain 57) (AICD-57) (AID(57)) (Gamma-CTF(57)); Gamma-secretase C-terminal fragment 50 (Amyloid intracellular domain 50) (AICD-50) (AID(50)) (Gamma-CTF(50)); C31]","pubmed":"25122912, 17062754, 23011729","uniprotid":"P05067","text":"FUNCTION: 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 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). 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. .; FUNCTION: 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.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. .; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6)."}],"geneconstraints_missense":2.252,"end_pos":"26171128","chromosome":21,"pdb":["1AAP","1AMB","1AMC","1AML","1BA4","1BA6","1BJB","1BJC","1BRC","1CA0","1HZ3","1IYT","1MWP","1OWT","1QCM","1QWP","1QXC","1QYT","1TAW","1TKN","1X11","1Z0Q","1ZE7","1ZE9","1ZJD","2BEG","2BP4","2FJZ","2FK1","2FK2","2FK3","2FKL","2FMA","2G47","2IPU","2LFM","2LLM","2LMN","2LMO","2LMP","2LMQ","2LNQ","2LOH","2LP1","2LZ3","2LZ4","2M4J","2M9R","2M9S","2MGT","2MJ1","2MPZ","2MVX","2MXU","2NAO","2OTK","2R0W","2WK3","2Y29","2Y2A","2Y3J","2Y3K","2Y3L","3AYU","3BAE","3BKJ","3DXC","3DXD","3DXE","3GCI","3IFL","3IFN","3IFO","3IFP","3JQ5","3JQL","3JTI","3KTM","3L33","3L81","3MOQ","3MXC","3MXY","3NYJ","3NYL","3OVJ","3OW9","3PZZ","3Q2X","3SV1","3U0T","3UMH","3UMI","3UMK","4HIX","4JFN","4M1C","4MDR","4MVI","4MVK","4MVL","4NGE","4OJF","4ONF","4ONG","4PQD","4PWQ","4XXD","5AEF","5AM8","5AMB","5BUO","5C67","5CSZ","5HOW","5HOX","5HOY","5KK3","5LFY","5LV0","5MY4","5MYO","5MYX","5ONP","5ONQ","5OQV","5TXD","5VOS","5VZY","5W3P","6CO3","6GFI","6ITU","6IYC","6NB9","6O4J","6OC9","6OIZ","6RHY","6SHS","6SZF","6TI5","6TI6","6TI7","6W0O","6WXM","6XOV","6YHF","6YHI","6YHO","6YHP","6YHX","7B3J","7B3K","7E6P","7F29","7JXN","7JXO","7O1Q","7OW1","7OXN","7Q4B","7Q4M","7RTZ","7U4P","7WFY","7WVY","7Y3J","7Y8Q","8AZS","8AZT","8B9Q","8B9R","8BFA","8BFB","8BFZ","8BG0","8C3H","8EZD","8EZE","8FF2","8FF3","8OL2","8OL3","8OL5","8OL6","8OL7","8OLG","8OLN","8OLO","8OLQ"],"geneconstraint":1,"description":"amyloid beta precursor protein","type":"protein-coding","start_pos":"25880550","clinvar_pathogenic":26,"genesymbol":"APP","changed_to":null,"geneconstraints_lof":0.999,"discontinued":null,"gene_no":351,"ensembl_gene_stable_id":["ENSG00000142192"],"geneconstraints_synonymous":0.388}]