Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.4.23.46

Official Name

memapsin 2

Name from literature

Beta-secretase

Pathway from literature

generation of the amyloid beta-peptide (Abeta) in Alzheimer disease

Pathway from KEGG

Human Diseases; Neurodegenerative Diseases; Alzheimer's disease; map05010

Organisms

Mouse (10090)

Genome localization

9 A5.2[23821 ],

Comments

Suggested to be the major "beta-secretase" responsible for the cleavage of the beta-amyloid precursor protein to form the amyloidogenic beta-peptide that is implicated in the pathology of Alzheimer's disease. In peptidase family A1 but is atypical in containing a C-terminal membrane-spanning domain.

Rate-limiting Description

"BACE1 exhibits all the properties of the beta-secretase, and as the key rate-limiting enzyme that initiates the formation of Abeta, BACE1 is an attractive drug target for AD." (11816789)

"Beta-secretase (BACE1) is the rate-limiting protease for the generation of the amyloid beta-peptide (Abeta) in Alzheimer disease." (15987683)

"Beta-secretase ." (beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the key rate-limiting enzyme for the production of the beta-amyloid (Abeta) peptide involved in the pathogenesis of Alzheimer's disease (AD))

"Amyloid-beta (Abeta) the primary component of the senile plaques found in Alzheimer's disease (AD) is generated by the rate-limiting cleavage of amyloid precursor protein (APP) by beta-secretase followed by gamma-secretase cleavage." (15452128)

"Beta-site APP cleaving enzyme-1 (BACE-1), is a rate-limiting enzyme for beta amyloid production." (18695518)

Regulatory Information

Upstream transcription factor

20846;18033;21405

Regulatory type

Detail

phosphorylation;

P56818

phosphorylation;

"serine phosphorylation of BACE is a physiologically relevant post-translational modification that regulates trafficking in the juxtanuclear compartment by interaction with GGA1" (15466887)

transcriptional factor;STAT1(20846)

"IFN-gamma activates JAK2 and ERK1/2 and then phosphorylated STAT1 binds to the putative STAT1 binding sequences in BACE1 promoter region to modulate BACE1 protein expression in astrocytes." (17091494)

transcriptional factor;HIF1(21405)

"important role for hypoxia/hypoxia inducible factor 1, alpha subunit in modulating the amyloidogenic processing of beta-amyloid precursor protein" (17303576)

transcriptional factor;NF-kappaB(18033)

"wild-type or Swedish mutated betaAPP overexpression modulates BACE1 promoter transactivation and activity via an NFkappaB-dependent pathway." (18263584)

Gene ontology

Gene ontology

GO:0005624 (C) membrane fraction [P56818 ];
GO:0050435 (P) beta-amyloid metabolic process [P56818 ];
GO:0030424 (C) axon [P56818 ];
GO:0006508 (P) proteolysis [P56818 ];
GO:0005768 (C) endosome [P56818 ];
GO:0031410 (C) cytoplasmic vesicle [P56818 ];
GO:0005794 (C) Golgi apparatus [P56818 ];
GO:0004190 (F) aspartic-type endopeptidase activity [P56818 ];
GO:0016021 (C) integral to membrane [P56818 ];

Subcellular localization

Localization

cell membrane [P56818 ];

Links

SwissProt

P56818

Entrez Gene

23821



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  Last Modified: 2009-03-24  
  Design by Zhao Min