Sortilin-related receptor; Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting. Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans- Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the e [...]

Beta-secretase 1; Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1 (By similarity).

Presenilin-1 CTF subunit; Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabili [...]

Amyloid-beta A4 precursor protein-binding family B member 1; Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1 [...]

Amyloid-beta A4 precursor protein-binding family A member 1; Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta.

Nicastrin; Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.

Tumor necrosis factor receptor superfamily member 21; Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP- beta which is further cleaved to release an N-terminal fra [...]

Clusterin alpha chain; [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and sub [...]

NEDD8-activating enzyme E1 regulatory subunit; Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.