Protein Domain : IPR008155

Type:  Family Name:  Amyloidogenic glycoprotein
Description:  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 [, ]. 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 []. 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 []. 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 []. 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: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). 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.This entry represents the family of amyloidogenic glycoproteins, such as amyloid-beta precursor protein (APP, or A4), Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). APP is an integral, glycosylated membrane protein. Short Name:  Amyloid_glyco
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1 Child Features

DB identifier Type Name
IPR028866 Family Amyloid beta A4 protein

9 Contains

DB identifier Type Name
IPR002223 Domain Pancreatic trypsin inhibitor Kunitz domain
IPR011178 Domain Amyloidogenic glycoprotein, copper-binding
IPR015849 Domain Amyloidogenic glycoprotein, heparin-binding
IPR013803 Domain Amyloidogenic glycoprotein, amyloid-beta peptide
IPR020901 Conserved_site Proteinase inhibitor I2, Kunitz, conserved site
IPR019543 Domain Beta-amyloid precursor protein C-terminal
IPR019745 Conserved_site Amyloidogenic glycoprotein, intracellular domain, conserved site
IPR019744 Conserved_site Amyloidogenic glycoprotein, extracellular domain conserved site
IPR008154 Domain Amyloidogenic glycoprotein, extracellular

1 Cross References

Identifier
PR00203

0 Found In

1 GO Annotation

GO Term Gene Name
GO:0016021 IPR008155

1 Ontology Annotations

GO Term Gene Name
GO:0016021 IPR008155

0 Parent Features

0 Proteins

4 Publications

First Author Title Year Journal Volume Pages PubMed ID
            12611883
            16301322
            16406235
            16364896