lmmol · Proteins

Amyloid-beta precursor protein

UniProt P05067 Organism Homo sapiens Gene A4, AD1, APP

Also known as: A4, AD1, APP

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. 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. 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.

Classification

Family (Pfam)
PF10515 APP_amyloid, PF12924 APP_Cu_bd, PF12925 APP_E2, PF02177 APP_N, PF03494 Beta-APP, PF00014 Kunitz_BPTI
InterPro
Amyloid_Cu-bd_sf, Amyloid_glyco, Amyloid_glyco_Abeta, Amyloid_glyco_Abeta_sf, Amyloid_glyco_Cu-bd, Amyloid_glyco_E2_domain, Amyloid_glyco_extra, Amyloid_glyco_heparin-bd, Amyloid_glyco_heparin-bd_sf, Amyloid_glyco_intracell_CS, APP_amyloid_C, APP_CUBD_CS, E2_sf, Kunitz_BPTI, Kunitz_BPTI_sf, PH-like_dom_sf, Prtase_inh_Kunz-CS
Functional cluster
Mur-Ligase Peptidoglycan Biosynthesis Enzymes

Experimental structures · PDB · 240

A predicted model is available from AlphaFold.

Gene Ontology · 125

Disease associations

Drugs targeting this protein · 2

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 171 cited papers

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