Beta-secretase 2

Beta-secretase 2 (EC 3.4.23.45, also known as Memapsin-1) is an enzyme^[5][6][7][8] that cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein. BACE2 is a close homolog of BACE1.

BACE2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EWY, 3ZKG, 3ZKI, 3ZKM, 3ZKN, 3ZKQ, 3ZKS, 3ZKX, 3ZL7, 3ZLQ, 4BEL, 4BFB
Identifiers
Aliases	BACE2, AEPLC, ALP56, ASP1, ASP21, BAE2, CDA13, CEAP1, DRAP, beta-site APP-cleaving enzyme 2, beta-secretase 2
External IDs	OMIM: 605668; MGI: 1860440; HomoloGene: 22696; GeneCards: BACE2; OMA:BACE2 - orthologs
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.2-q22.3 Start 41,167,801 bp[1] End 41,282,530 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 C4 Start 97,157,942 bp[2] End 97,244,136 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland gallbladder pancreatic ductal cell minor salivary glands renal medulla islet of Langerhans pylorus ascending aorta Descending thoracic aorta saphenous vein Top expressed in pyloric antrum epithelium of stomach transitional epithelium of urinary bladder islet of Langerhans iris mucous cell of stomach sciatic nerve conjunctival fornix aortic valve stria vascularis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity amyloid-beta binding hydrolase activity aspartic-type endopeptidase activity Cellular component integral component of membrane cell surface endosome Golgi apparatus endoplasmic reticulum membrane plasma membrane cytoplasm trans-Golgi network dense core granule Biological process peptide hormone processing protein catabolic process amyloid-beta metabolic process negative regulation of amyloid precursor protein biosynthetic process proteolysis membrane protein ectodomain proteolysis astrocyte activation glucose homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25825 56175 Ensembl ENSG00000182240 ENSMUSG00000040605 UniProt Q9Y5Z0 Q9JL18 RefSeq (mRNA) NM_138992 NM_012105 NM_138991 NM_019517 RefSeq (protein) NP_036237 NP_620476 NP_620477 NP_062390 Location (UCSC) Chr 21: 41.17 – 41.28 Mb Chr 16: 97.16 – 97.24 Mb PubMed search [3] [4]
Wikidata
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Gene

This gene is located in the "Down critical region" of chromosome 21, which has been implicated in the pathogenesis of Down syndrome. Three transcript variants encoding different isoforms have been described for this gene.^[8]

Function

See also: integral membrane protein and glycoprotein

The protein encoded by this gene is a member of the peptidase A1 family, and functions as a type I integral membrane glycoprotein and aspartic protease. It is involved in the proteolytic cleavage of amyloid precursor protein (APP), a key step in the production of amyloid beta peptide. Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a common complication in Down syndrome.

BACE2 has also been identified as the primary protease responsible for the release of the amyloidogenic ectodomain of Pmel17 in melanocytes, a process essential for the formation of the melanosome amyloid matrix.^[9]

Clinical significance

BACE2 has been implicated in the maintenance of pancreatic β cells and regulation of glucose homeostasis. In mouse models, higher BACE2 activity has been associated with improved pancreatic function, suggesting potential therapeutic relevance for Type 2 Diabetes research.^[10] In a separate context, a homozygous 25-base pair deletion in the BACE2 gene has been linked to the unique brown-and-white coat coloration in some giant pandas, as opposed to the typical black-and-white phenotype observed in the wild type.^[11]

Interactions

BACE2 has been shown to interact with GGA1^[12] and GGA2.^[12]