Family

Beta-secretase BACE2 (IPR009121)

Short name: BACE2

Family relationships

Description

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 memapsin 2 or 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.

BACE2, also termed Asp1 and memapsin 2, was initially identified though Expressed Sequence Tag (EST) database searching. In vitro enzymatic assays with peptide substrates have demonstrated that BACE2 cleaves beta- secretase substrates in a similar fashion to BACE1 [PMID: 10931940]. The BACE2 mRNA is expressed in the central nervous system and many peripheral tissues, although its expression level in neurons is substantially lower than that of BACE1 [PMID: 10749877].

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.
PANTHER
PRINTS