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).
Subcellular locations: Cell membrane, Golgi apparatus, Trans-Golgi network, Endoplasmic reticulum, Endosome, Cell surface, Cytoplasmic vesicle membrane, Membrane raft, Lysosome, Late endosome, Early endosome, Recycling endosome, Cell projection, Axon, Cell projection, Dendrite
Predominantly localized to the later Golgi/trans-Golgi network (TGN) and minimally detectable in the early Golgi compartments. A small portion is also found in the endoplasmic reticulum, endosomes and on the cell surface (, ). Colocalization with APP in early endosomes is due to addition of bisecting N-acetylglucosamine wich blocks targeting to late endosomes and lysosomes (By similarity). Retrogradly transported from endosomal compartments to the trans-Golgi network in a phosphorylation- and GGA1- dependent manner .
Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.