Protein: Beta-secretase 2 (EC 3.4.23.45) (Aspartyl protease 1) (ASP1) (Asp 1) (Beta-site amyloid precursor protein cleaving enzyme 2) (Beta-site APP cleaving enzyme 2) (Memapsin-1) (Membrane-associated aspartic protease 1) (Theta-secretase) (Q9JL18)
Organism: Mus musculus (Mouse)
Function: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672. Involved in the proteolytic shedding of PMEL at early stages of melanosome biogenesis. Cleaves PMEL within the M-beta fragment to release the amyloidogenic PMEL luminal fragment containing M-alpha and a small portion of M-beta N-terminus. This is a prerequisite step for subsequent processing and assembly of PMEL fibrils into amyloid sheets. Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells.
Subcellular location: Cell membrane {ECO:0000269|PubMed:21907142}; Single-pass type I membrane protein {ECO:0000250}. Golgi apparatus {ECO:0000250|UniProtKB:Q9Y5Z0}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9Y5Z0}. Endosome {ECO:0000250|UniProtKB:Q9Y5Z0}. Melanosome {ECO:0000250|UniProtKB:Q9Y5Z0}. Note=Colocalizes with PMEL in stage I and II melanosomes. {ECO:0000250|UniProtKB:Q9Y5Z0}.
Sequence: MGALLRALLLLVLAQWLLSAVPALAPAPFTLPLQVAGATNHRASAVPGLGTPELPRADGLALALEPVRATANFLAMVDNLQGDSGRGYYLEMLIGTPPQKVQILVDTGSSNFAVAGAPHSYIDTYFDSESSSTYHSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNSSFLVNIATIFESENFFLPGIKWNGILGLAYAALAKPSSSLETFFDSLVAQAKIPDIFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKEEWYYQIEILKLEIGGQNLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARTSLIPEFSDGFWTGAQLACWTNSETPWAYFPKISIYLRDENASRSFRITILPQLYIQPMMGAGFNYECYRFGISSSTNALVIGATVMEGFYVVFDRAQRRVGFAVSPCAEIEGTTVSEISGPFSTEDIASNCVPAQALNEPILWIVSYALMSVCGAILLVLILLLLLPLHCRHAPRDPEVVNDESSLVRHRWK
InterPro domains: - IPR033121: Peptidase family A1 domain (domain) [88-425]
- IPR001461: Aspartic peptidase A1 (family) [8-435]
- IPR009121: Beta-secretase BACE2 (family) [115-474]
- IPR021109: Aspartic peptidase domain superfamily (homologous_superfamily) [77-456]
- IPR001969: Aspartic peptidase, active site (active_site) [103-114]
- IPR033874: Memapsin-like (domain) [85-446]
- IPR009119: Beta-secretase BACE (family) [112-482]
Interaction partners: - Reticulon-3
- Reticulon-4
- Beta-secretase 1
- Amyloid-beta precursor protein
- Tyrosine-protein kinase Fyn
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0004175 (endopeptidase activity), GO:0070001 (aspartic-type peptidase activity), GO:0004190 (aspartic-type endopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0042592 (homeostatic process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0043473 (pigmentation), GO:0048519 (negative regulation of biological process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0009892 (negative regulation of metabolic process), GO:0019222 (regulation of metabolic process), GO:0033059 (cellular pigmentation), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0048871 (multicellular organismal-level homeostasis), GO:0048523 (negative regulation of cellular process), GO:0002262 (myeloid cell homeostasis), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0009888 (tissue development), GO:0030154 (cell differentiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0048753 (pigment granule organization), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0060249 (anatomical structure homeostasis), GO:0006508 (proteolysis), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0008544 (epidermis development), GO:0051248 (negative regulation of protein metabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0030318 (melanocyte differentiation), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:1903018 (regulation of glycoprotein metabolic process), GO:0060429 (epithelium development), GO:0006996 (organelle organization), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:0016050 (vesicle organization), GO:0033619 (membrane protein proteolysis), GO:2000113 (negative regulation of cellular macromolecule biosynthetic process), GO:0010559 (regulation of glycoprotein biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005794 (Golgi apparatus), GO:0031090 (organelle membrane), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0030667 (secretory granule membrane), GO:0099503 (secretory vesicle), GO:0031045 (dense core granule), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0031982 (vesicle), GO:0012506 (vesicle membrane), GO:0030659 (cytoplasmic vesicle membrane), GO:0097708 (intracellular vesicle)