Summary for peptidase A01.004: memapsin-2

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namememapsin-2
Other namesAsp2 protease, BACE1 g.p. (Homo sapiens), beta-secretase, beta-site APP-cleaving enzyme
Domain architecture
MEROPS Classification
Classification Clan AA >> Subclan (none) >> Family A1 >> Subfamily A >> A01.004
Holotypememapsin-2 (Homo sapiens), Uniprot accession P56817 (peptidase unit: 52-428), MERNUM MER0005870
History Identifier created: MEROPS 3.4 (5 November 1999)
Activity
Catalytic typeAspartic
PeplistIncluded in the Peplist with identifier PL00003
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.23 (Aspartic endopeptidases) >> Peptidase 3.4.23.46
EnzymologyBRENDA database
Proteolytic eventsCutDB database (7 cleavages)
Activity statushuman: active (Tang & Koelsch, 2004)
mouse: active (Ohno et al., 2004)
PhysiologyRoberds et al. (2001) concluded that this enzyme is the primary beta-secretase activity in mouse brain.
KnockoutA mouse gene knockout model showed that loss of beta-secretase activity led to a reduction in beta-amyloid peptide production but no profound phenotypic defects (Roberds et al., 2001). Upregulation in mouse, in the background of over-expressed Alzheimer"s precursor protein, was studied by Chiocco et al. (2004).
Pharmaceutical relevanceMemapsin-2 is a transmembrane aspartic endopeptidase that has beta-secretase activity, and may therefore be a drug target for Alzheimer"s disease (Ghosh et al., 2002). However, an initial report that it could be deleted in mouse without adverse effects (Roberds et al., 2001) was later denied (Laird et al., 2005), raising issues that need to be considered in relation to the potential of memapsin-2 as a therapeutic target for treatment of Alzheimer"s disease.
Pathways KEGGAlzheimer's disease
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Memapsin_2
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patterneg/vil/-/lfScissile bond-/av/-/vf (based on 24 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 6 1 1 1 3 0 2 0
Pro 0 0 1 0 0 0 0 0
Ala 2 0 1 1 2 8 1 2
Val 1 8 1 2 0 8 3 6
Leu 0 4 1 10 0 0 4 3
Ile 0 5 1 0 1 1 2 0
Met 0 0 0 2 2 0 0 0
Phe 0 1 1 4 0 0 0 5
Tyr 0 0 1 1 0 0 0 1
Trp 0 0 0 0 0 0 0 0
Ser 1 2 0 1 3 2 0 0
Thr 1 1 1 0 2 1 1 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 5 0 0 0 1 0
Gln 0 0 1 0 3 0 0 0
Asp 0 0 2 0 5 0 1 3
Glu 7 1 2 0 3 2 5 2
Lys 2 0 2 0 0 0 2 0
Arg 1 0 0 1 0 1 1 1
His 1 0 1 1 0 1 1 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
BACE1 11q23.3-q24.1 ENSG00000160610 23621 BACE 604252
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Bace 9:B ENSMUSG00000032086 23821 MGI:1346542