| IED ID | IndEnz0002014491 |
| Enzyme Type ID | protease014491 |
| Protein Name |
Beta-secretase 1 EC 3.4.23.46 Beta-site amyloid precursor protein cleaving enzyme 1 Beta-site APP cleaving enzyme 1 Memapsin-2 Membrane-associated aspartic protease 2 |
| Gene Name | BACE1 |
| Organism | Cavia porcellus (Guinea pig) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Hystricomorpha Caviidae (cavies) Cavia (guinea pigs) Cavia porcellus (Guinea pig) |
| Enzyme Sequence | MAPALPWLLLWVGSGVLPVHGTQDGIRLPLRSGLAGAPLGLRLPRETDEEPGRRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQRSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGILGLAYAEIARLCGAGFPLNQSEAVASVGGSMIIGGIDHSLYTGNLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTATVEGPFVTPDMEDCGYNIPQTDESTLMTIAYVMAAICALFMLPLCLMVCQWRCLRCLRHQHDDFADDISLLK |
| Enzyme Length | 473 |
| Uniprot Accession Number | Q1KLR6 |
| Absorption | |
| Active Site | ACT_SITE 90; /evidence=ECO:0000255|PROSITE-ProRule:PRU10094; ACT_SITE 261; /evidence=ECO:0000255|PROSITE-ProRule:PRU10094 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by RTN3 and RTN4. {ECO:0000250|UniProtKB:P56817}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.; EC=3.4.23.46; Evidence={ECO:0000250|UniProtKB:P56817}; |
| DNA Binding | |
| EC Number | 3.4.23.46 |
| Enzyme Function | 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 (By similarity). Cleaves CHL1 (By similarity). {ECO:0000250|UniProtKB:P56817, ECO:0000250|UniProtKB:P56818}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Cross-link (1); Disulfide bond (3); Domain (1); Glycosylation (4); Lipidation (4); Modified residue (8); Motif (1); Propeptide (1); Region (1); Signal peptide (1); Topological domain (2); Transmembrane (1) |
| Keywords | Acetylation;Aspartyl protease;Cell membrane;Cell projection;Cytoplasmic vesicle;Disulfide bond;Endoplasmic reticulum;Endosome;Glycoprotein;Golgi apparatus;Hydrolase;Isopeptide bond;Lipoprotein;Lysosome;Membrane;Palmitate;Phosphoprotein;Protease;Reference proteome;Signal;Transmembrane;Transmembrane helix;Ubl conjugation;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P56817}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P56817}. Golgi apparatus, trans-Golgi network {ECO:0000250|UniProtKB:P56817}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P56817}. Endosome {ECO:0000250|UniProtKB:P56817}. Cell surface {ECO:0000250|UniProtKB:P56817}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P56817}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P56817}. Membrane raft {ECO:0000250|UniProtKB:P56818}. Lysosome {ECO:0000250|UniProtKB:P56817}. Late endosome {ECO:0000250|UniProtKB:P56817}. Early endosome {ECO:0000250|UniProtKB:P56817}. Recycling endosome {ECO:0000250|UniProtKB:P56817}. 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P56817, ECO:0000250|UniProtKB:P56818}. |
| Modified Residue | MOD_RES 123; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 247; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 251; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 257; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 271; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 272; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 279; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P56817; MOD_RES 470; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P56818 |
| Post Translational Modification | PTM: Palmitoylation mediates lipid raft localization. {ECO:0000250|UniProtKB:P56818}.; PTM: Acetylated in the endoplasmic reticulum at Lys-123, Lys-247, Lys-251, Lys-257, Lys-271, Lys-272, and Lys-279. Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein. {ECO:0000250|UniProtKB:P56817}.; PTM: Ubiquitinated at Lys-473, ubiquitination leads to lysosomal degradation. Monoubiquitinated and 'Lys-63'-linked polyubitinated. Deubiquitnated by USP8; inhibits lysosomal degradation. {ECO:0000250|UniProtKB:P56817}.; PTM: Phosphorylation at Ser-470 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network. Non-phosphorylated BACE1 enters a direct recycling route to the cell surface. {ECO:0000250|UniProtKB:P56817}.; PTM: N-Glycosylated (By similarity). Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions (By similarity). {ECO:0000250|UniProtKB:P56817, ECO:0000250|UniProtKB:P56818}. |
| Signal Peptide | SIGNAL 1..21; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 468..472; /note=DXXLL; /evidence=ECO:0000250|UniProtKB:P56817 |
| Gene Encoded By | |
| Mass | 52,576 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |