|SMART accession number:||SM00006|
|Description:||amyloid A4 precursor of Alzheimers disease|
|Interpro abstract (IPR008154):|
Amyloid-beta precursor protein (APP, or A4) is associated with Alzheimer's disease (AD), because one of its breakdown products, amyloid-beta (A-beta), aggregates to form amyloid or senile plaques [(PUBMED:16301322), (PUBMED:16364896)]. Mutations in APP or in proteins that process APP have been linked with early-onset, familial AD. Individuals with Down's syndrome carry an extra copy of chromosome 21, which contains the APP gene, and almost invariably develop amyloid plaques and Alzheimer's symptoms.
APP is important for the neurogenesis and neuronal regeneration, either through the intact protein, or through its many breakdown products [(PUBMED:16406235)]. APP consists of a large N-terminal extracellular region containing heparin-binding and copper-binding sites, a short hydrophobic transmembrane domain, and a short C-terminal intracellular domain. The N-terminal region is similar in structure to cysteine-rich growth factors and appears to function as a cell surface receptor, contributing to neurite growth, neuronal adhesion, axonogenesis and cell mobility [(PUBMED:16406235)]. APP acts as a kinesin I membrane receptor to mediate the axonal transport of beta-secretase and presenilin 1. The N-terminal domain can regulate neurite outgrowth through its binding to heparin and collagen I and IV, which are components of the extracellular matrix. APP is also coupled to apoptosis-inducing pathways, and is involved in copper homeostasis/oxidative stress through copper ion reduction, where copper-metallated APP induces neuronal death [(PUBMED:12611883)]. The C-terminal intracellular domain appears to be involved in transcription regulation through protein-protein interactions. APP can promote transcription activation through binding to APBB1/Tip60, and may bind to the adaptor protein FE65 to transactivate a wide variety of different promoters.
APP can be processed by different sets of enzymes:
This entry represents an extracellular domain that is usually found at the N-terminal of amyloidogenic glycoproteins such as amyloid-beta precursor protein (APP, or A4).
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