BACE1
GeneName
BACE1
Summary
BACE1, also known as BACE-1 or Asp2, is a 56 kDa aspartic protease predominantly expressed in the brain, particularly in neurons. It is localised to various cellular compartments including the plasma membrane, endosomes, and the Golgi apparatus. BACE1 plays a critical role in the amyloid precursor protein (APP) catabolic process, facilitating the production of amyloid-beta, a key player in Alzheimer’s disease pathology. Its enzymatic activity involves the cleavage of membrane proteins, contributing to processes such as presynaptic modulation and neuronal apoptosis. BACE1 is also implicated in the cellular response to metal ions and sensory perception mechanisms.
Importance
BACE1 is relevant to: - Alzheimer’s disease research due to its role in amyloid-beta production, making it a target for therapeutic intervention. - Understanding synaptic transmission and plasticity, as it influences presynaptic modulation. - Investigating the mechanisms of neuronal apoptosis, providing insights into neurodegenerative processes. - Exploring the cellular responses to metal ions, which may have implications in neurotoxicity and related disorders.
Top Products
For researchers investigating BACE1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-BACE1 antibody (ab2077), which has garnered 94 citations, reflecting its reliability in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). This antibody is a trusted choice for those looking to study BACE1 in various contexts.Additionally, we offer the recombinant antibody, Anti-BACE1 antibody [EPR3956] (ab108394), which has been validated in knockout models and is suitable for Western blotting (WB) and immunoprecipitation (IP). With 76 citations, this monoclonal antibody is ideal for researchers seeking the consistency and specificity that recombinant antibodies provide. Together, these products offer robust options for studying BACE1 effectively. The Anti-BACE1 antibody ELISA Kit (ab10716), supported by 9 citations, is an excellent option for researchers looking to accurately measure BACE1 levels in their samples.
Abcam Product Citation Summary
The data indicates a strong focus on the role of BACE1 in various contexts related to Alzheimer's disease and amyloid-β production. Multiple studies utilise Western blotting and immunohistochemistry techniques across human and mouse models, particularly in brain tissues. The research highlights the importance of BACE1 in APP processing and its implications in neurodegenerative conditions.
Abcam Product Citation Table
Domain
DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation.
The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.
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 (PubMed:10656250, PubMed:10677483, PubMed:20354142). Cleaves CHL1 (By similarity).
Post-translational modifications
N-Glycosylated (PubMed:11083922, PubMed:17425515). Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions (By similarity).
Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307. 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.
Palmitoylation mediates lipid raft localization.
Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation (PubMed:16033761, PubMed:20484053, PubMed:23109336, PubMed:27302062). Monoubiquitinated and 'Lys-63'-linked polyubitinated (PubMed:20484053). Deubiquitnated by USP8; inhibits lysosomal degradation (PubMed:27302062).
Phosphorylation at Ser-498 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.
Sequence Similarities
Belongs to the peptidase A1 family.
Tissue Specificity
Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Golgi apparatus
- trans-Golgi network
- Endoplasmic reticulum
- Endosome
- Cell surface
- Cytoplasmic vesicle membrane
- Single-pass type I membrane protein
- 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 (PubMed:11466313, PubMed:17425515). 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 (PubMed:15886016).
Alternative names
BACE, KIAA1149, BACE1, Beta-secretase 1, Aspartyl protease 2, Beta-site amyloid precursor protein cleaving enzyme 1, Memapsin-2, Membrane-associated aspartic protease 2, ASP2, Asp 2, Beta-site APP cleaving enzyme 1