Protein: Beta-secretase 1 (EC 3.4.23.46) (Aspartyl protease 2) (ASP2) (Asp 2) (Beta-site amyloid precursor protein cleaving enzyme 1) (Beta-site APP cleaving enzyme 1) (Memapsin-2) (Membrane-associated aspartic protease 2) (P56817)
Organism: Homo sapiens (Human)
Function: 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 location: Cell membrane {ECO:0000269|PubMed:11466313}; Single-pass type I membrane protein {ECO:0000305|PubMed:11466313}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:17425515, ECO:0000269|PubMed:20354142, ECO:0000269|PubMed:23109336}. Endoplasmic reticulum {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:17425515}. Endosome {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016}. Cell surface {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:17425515, ECO:0000269|PubMed:23109336}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016}; Single-pass type I membrane protein {ECO:0000305|PubMed:11466313}. Membrane raft {ECO:0000250|UniProtKB:P56818}. Lysosome {ECO:0000269|PubMed:16033761, ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27084579, ECO:0000269|PubMed:27302062}. Late endosome {ECO:0000269|PubMed:16033761, ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27084579, ECO:0000269|PubMed:27302062}. Early endosome {ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27084579, ECO:0000269|PubMed:27302062}. Recycling endosome {ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:27084579, ECO:0000269|PubMed:27302062}. Cell projection, axon {ECO:0000250|UniProtKB:P56818}. Cell projection, dendrite {ECO:0000250|UniProtKB:P56818}. Note=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 (PubMed:11466313, PubMed:17425515). Colocalization with APP in early endosomes is due to addition of bisecting N-acetylglucosamine which 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 (PubMed:15886016). {ECO:0000250|UniProtKB:P56818, ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:17425515}.
Interaction partners:
- Amyloid-beta precursor protein
- Reticulon-4
- Reticulon-3
- ADP-ribosylation factor-binding protein GGA1
- Presenilin-1
- ADP-ribosylation factor-binding protein GGA3
- Disintegrin and metalloproteinase domain-containing protein 10
- Beta-secretase 2
- Immunoglobulin heavy variable 3-43D
- Nicastrin
Sequence:
MAQALPWLLLWMGAGVLPAHGTQHGIRLPLRSGLGGAPLGLRLPRETDEEPEEPGRRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESTLMTIAYVMAAICALFMLPLCLMVCQWRCLRCLRQQHDDFADDISLLK