Beta-Site APP Cleaving Enzyme 1 (bACE1)

ASP2; Beta Secretase; Memapsin 2; Aspartyl protease 2; Beta-site amyloid precursor protein cleaving enzyme 1; Membrane-associated aspartic protease 2

SPN	W094
HGNC	933
MGI	1346542
PubMed	14701757
RGD	2191
UniProt	P56817
Wiki	Beta_secretase

β-Secretaseis an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. The transmembrane protein, contains two active site aspartate residues in its extracellular protein domain and may function as a dimer.Generation of the 40 or 42 amino acid-long amyloid-β peptides that aggregate in the brain of Alzheimer's patients requires two sequential cleavages of the amyloid precursor protein (APP). Extracellular cleavage of APP by BACE releases a soluble extracellular fragment and is followed by APP cleavage within its transmembrane domain by γ-secretase. The second cleavage releases the intracellular domain of APP and amyloid-β. Since alpha-secretase cleaves APP closer to the cell membrane than BACE does.

Reference

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Science 286:735-741(1999) [PubMed] [Europe PMC] [Abstract]

"Purification and cloning of amyloid precursor protein beta-secretase from human brain."
Nature 402:537-540(1999) [PubMed] [Europe PMC] [Abstract]

"Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity."
Nature 402:533-537(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of a novel aspartic proteinase (Asp 2) as beta-secretase."
Mol. Cell. Neurosci. 14:419-427(1999) [PubMed] [Europe PMC] [Abstract]

"Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production."
Neurosci. Lett. 307:9-12(2001) [PubMed] [Europe PMC] [Abstract]

"Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain."
DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract]

"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein."
Proc. Natl. Acad. Sci. U.S.A. 97:1456-1460(2000) [PubMed] [Europe PMC] [Abstract]

"ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site."
Mol. Cell. Neurosci. 16:609-619(2000) [PubMed] [Europe PMC] [Abstract]

"The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate."
J. Biol. Chem. 276:36788-36796(2001) [PubMed] [Europe PMC] [Abstract]

"The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity."
J. Neurochem. 80:1079-1088(2002) [PubMed] [Europe PMC] [Abstract]

"Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins."
Biochemistry 42:12174-12180(2003) [PubMed] [Europe PMC] [Abstract]

"Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation."
Nat. Med. 10:959-965(2004) [PubMed] [Europe PMC] [Abstract]

"Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein."
Eur. J. Neurosci. 24:1237-1244(2006) [PubMed] [Europe PMC] [Abstract]

"Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins."
J. Mol. Biol. 363:625-634(2006) [PubMed] [Europe PMC] [Abstract]

"A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1."
Biochem. J. 407:383-395(2007) [PubMed] [Europe PMC] [Abstract]

"PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1."
EMBO Rep. 9:916-922(2008) [PubMed] [Europe PMC] [Abstract]

"Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels."
J. Biol. Chem. 284:2482-2492(2009) [PubMed] [Europe PMC] [Abstract]

"Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing."
FASEB J. 24:2783-2794(2010) [PubMed] [Europe PMC] [Abstract]

"Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor."
Science 290:150-153(2000) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3."
Biochemistry 41:10963-10967(2002) [PubMed] [Europe PMC] [Abstract]

"Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis."
Biochemistry 43:4689-4695(2004) [PubMed] [Europe PMC] [Abstract]

"Apo and inhibitor complex structures of BACE (beta-secretase)."
J. Mol. Biol. 343:407-416(2004) [PubMed] [Europe PMC] [Abstract]

"Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase)."
Biochemistry 44:105-112(2005) [PubMed] [Europe PMC] [Abstract]