Parkinson
Parkinson
Parkinson
Function
Functions as a cell surface receptor and performs physiological functions on the surface of
neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell
mobility and transcription regulation through protein-protein interactions. Can promote
transcription activation through binding to APBB1-KAT5 and inhibit 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. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can
regulate neurite outgrowth through binding to components of the extracellular matrix such as
heparin and collagen I and IV (By similarity). 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 (By similarity). Provides Cu2+ ions for
GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the
heparan sulfate chains on GPC1.
Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Binds
transient metals such as copper, zinc and iron. Rat and mouse amyloid-beta peptides bind
only weakly transient metals and have little reducing activity due to substitutions of transient
metal chelating residues. Amyloid-beta protein 42 may activate mononuclear phagocytes in
the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK
II-mediated phosphorylation. Also binds GPC1 in lipid rafts.
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent
enhancers of neuronal apoptosis.
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell
bodies (via caspase-3) and axons (via caspase-6).
Miscellaneous
Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between
amyloid-beta molecules resulting in amyloid-beta-metal aggregates. Rat and mouse
amyloid-beta peptides have an arginine residue substituted for the bridging histidine residue
and are thus less capable of forming amyloid aggregates. Extracellular zinc-binding increases
binding of heparin to APP and inhibits collagen-binding (By similarity).
Amyloid beta A4 protein Subcellular Location
Reference:
[1] Lorenzo M. Refolo, Miguel A. Pappolla et al.. (2000). Hypercholesterolemia Accelerates
the Alzheimer’s Amyloid Pathology in a Transgenic Mouse Model. 07/03/2018, from
ELSEVIER Website:
https://ac.els-cdn.com/S0969996100903048/1-s2.0-S0969996100903048-main.pdf?_tid=c35
2b9d3-ad8c-4561-89f5-0b5647189876&acdnat=1520464751_8653e7165c4ef760538428059
96e86cd
[2] Uniprot. 07/03/2018 from Website: http://www.uniprot.org/uniprot/P28867
[3] Uniprot. 07/03/2018 from Website: http://www.uniprot.org/uniprot/Q61072
[4] Uniprot. 07/03/2018 from Website: http://www.uniprot.org/uniprot/Q61072
[5] Uniprot. 07/03/2018 from Website: http://www.uniprot.org/uniprot/Q8CHK4
[6]Uniprot. 07/03/2018 from Website: http://www.uniprot.org/uniprot/O88447