Beta-secretase BACE (IPR009119)

Short name: BACE

Family relationships


One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the progressive formation in the brain of insoluble amyloid plaques and vascular deposits consisting of beta-amyloid protein (beta-APP) [PMID: 6375662]. Production of beta-APP requires proteolytic cleavage of the large type-1 transmembrane (TM) protein amyloid precursor protein (APP) [PMID: 2881207]. This process is performed by a variety of enzymes known as secretases. To initiate beta-APP formation, beta-secretase cleaves APP to release a soluble N-terminal fragment (APPsBeta) and a C-terminal fragment that remains membrane bound. This fragment is subsequently cleaved by gamma-secretase to liberate beta-APP.

Several independent studies identified a novel TM aspartic protease as the major beta-secretase [PMID: 10531052, PMID: 10656250, PMID: 10591213]. This protein, termed beta-site APP cleaving enzyme 1 (BACE1), shares 64% amino acid sequence similarity with a second enzyme, termed BACE2. Together, BACE1 and BACE2 define a novel family of aspartyl proteases [PMID: 12391600]. Both enzymes share significant sequence similarity with other members of the pepsin family of aspartyl proteases and contain the two characteristic D(T/S)G(T/S) motifs that form the catalytic site. However, by contrast with other aspartyl proteases, BACE1 and BACE2 are type I TM proteins. Each protein comprises a large lumenal domain containing the active centre, a single TM domain and a small cytoplasmic tail.

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004190 aspartic-type endopeptidase activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.