Amyloidogenic glycoprotein, extracellular domain conserved site
InterPro Protein Domain record
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description
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<p>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 [<cite idref="PUB00033916"/>, <cite idref="PUB00033918"/>]. 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.</p><p> APP is important for the neurogenesis and neuronal regeneration, either through the intact protein, or through its many breakdown products [<cite idref="PUB00033917"/>]. 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 [<cite idref="PUB00033917"/>]. 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 [<cite idref="PUB00029624"/>]. 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.</p><p>APP can be processed by different sets of enzymes:</p><p> <ul><li> In the non-amyloidogenic (non-plaque-forming) pathway, APP is cleaved by alpha-secretase to yield a soluble N-terminal sAPP-alpha (neuroprotective) and a membrane-bound CTF-alpha. CTF-alpha is broken-down by presenilin-containing gamma-secretase to yield soluble p3 and membrane-bound AICD (nuclear signalling). </li><li>In the amyloidogenic pathway (plaque-forming), APP is broken down by beta-secretase to yield soluble sAPP-beta and membrane-bound CTF-beta. CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact.</li></ul> </p><p>This entry represents a conserved sequence of the the extra-cellular domain, it is located near the beginning of the extracellular domain. </p><p>More information about these protein can be found at Protein of the Month: Amyloid-beta Precursor Protein [<cite idref="PUB00033943"/>].</p>
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Amyloidogenic glycoprotein, extracellular domain conserved site
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InterPro Protein Domain record
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