BACE2
Beta-Secretase 2: A Key Aspartic Protease in Amyloid Processing and Cellular Signaling
Gene Information Card
| Symbol | BACE2 |
|---|---|
| Full Name | Beta-secretase 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 25825 ncbi.nlm.nih.gov/gene/25825 |
| Ensembl ID | ENSG00000182240 |
| UniProt ID | Q9Y5Z0 |
| OMIM ID | 605668 |
| HGNC ID | 943 |
| Aliases | ASP1, BACE2, DRAP, AEP2, ALP56, ASP-1, BACE2-1, BACE2-2, CDA13, MGC131853 |
Description
BACE2 (beta-secretase 2) is a member of the aspartic protease family, closely related to BACE1. It is encoded on chromosome 21q22.3 and is involved in the processing of amyloid precursor protein (APP) and other substrates. BACE2 is expressed in various tissues, including the brain, pancreas, and kidney, and has been implicated in Alzheimer disease, Down syndrome, and type 2 diabetes. Its activity can either promote or inhibit amyloid-beta production depending on the cleavage site within APP.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | BACE2 cleaves APP at alternative sites, potentially reducing amyloid-beta production; altered expression may modulate disease risk. | ClinVar, OMIM |
| Down syndrome | BACE2 is located on chromosome 21; trisomy 21 leads to increased gene dosage, which may affect APP processing and contribute to early-onset Alzheimer pathology. | OMIM, NCBI |
| Type 2 diabetes | BACE2 is expressed in pancreatic beta cells and processes islet amyloid polypeptide (IAPP); dysregulation may contribute to beta-cell dysfunction. | UniProt, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 3.2 | Medium |
| Pancreas | 8.5 | High |
| Kidney | 4.1 | Medium |
| Testis | 2.0 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 2.8 | Neuroblastoma cell line; moderate expression |
| HEK293 | 3.5 | Embryonic kidney cells; used for functional studies |
| MCF7 | 1.2 | Breast cancer cell line; low expression |
| HepG2 | 1.0 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | Uncertain significance; reported in ClinVar |
| c.1234C>T | Nonsense | <0.01% | Predicted loss of function; rare |
| c.567G>A | Missense | <0.01% | May affect catalytic activity; limited evidence |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations that truncate the protein or disrupt the catalytic aspartic acid residues (e.g., D93, D289) are predicted to cause loss of enzymatic activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations have been reported in BACE2.
Dominant Negative (DN)
No dominant-negative mutations have been described for BACE2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Alzheimer disease - amyloid fiber formation (Reactome: R-HSA-977225)
• Amyloid precursor protein processing (Reactome: R-HSA-8866427)
• Beta-secretase pathway (KEGG: hsa05010)
Protein Summary
BACE2 is a 518-amino acid transmembrane aspartic protease with a signal peptide, a propeptide, and a catalytic domain containing two conserved aspartic acid residues (D93 and D289) essential for proteolytic activity. It is synthesized as a zymogen and activated by furin cleavage. BACE2 localizes to the Golgi apparatus, endosomes, and plasma membrane. It cleaves APP at the beta-secretase site (similar to BACE1) but also at the theta-secretase site, which may reduce amyloid-beta production. Additionally, BACE2 processes other substrates such as IAPP, P-selectin glycoprotein ligand-1, and voltage-gated sodium channels. Its expression is regulated by transcription factors including SP1 and NF-kB.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BACE2 Knockout HEK293 Cell Line | EDJ-KQ2355 | Human | 25825 | Details Get a Quote |
| BACE2 Knockout HCT 116 Cell Line | EDJ-KQ21465 | Human | 25825 | Details Get a Quote |
| BACE2 Knockout A-549 Cell Line | EDJ-KQ22787 | Human | 25825 | Details Get a Quote |
| BACE2 Knockout HeLa Cell Line | EDJ-KQ22789 | Human | 25825 | Details Get a Quote |
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