| Primary Identifier | IPR009119 | Type | Family |
| Short Name | BACE |
| 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) [].Production of beta-APP requires proteolytic cleavage of the large type-1 transmembrane (TM) protein amyloid precursor protein (APP) []. This processis 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 themajor beta-secretase [, , ]. This protein, termed beta-site APP cleavingenzyme 1 (BACE1), shares 64% amino acid sequence similarity with a secondenzyme, termed BACE2. Together, BACE1 and BACE2 define a novel family of aspartyl proteases []. Both enzymes share significant sequence similaritywith 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 aretype I TM proteins. Each protein comprises a large lumenal domain containingthe active centre, a single TM domain and a small cytoplasmic tail. |
