Summary for peptidase A22.001: presenilin 1

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

 

Names
MEROPS Namepresenilin 1
Other namesminilin, PS1, PSEN1 g.p. (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan AD >> Subclan (none) >> Family A22 >> Subfamily A >> A22.001
Holotypepresenilin 1 (Homo sapiens), Uniprot accession P49768 (peptidase unit: 1-467), MERNUM MER0005221
History Identifier created: MEROPS 3.30 (20 July 1999)
Activity
Catalytic typeAspartic
PeplistIncluded in the Peplist with identifier PL00426
NC-IUBMBNot yet included in IUBMB recommendations.
Proteolytic eventsCutDB database (11 cleavages)
Activity statushuman: active (Esler et al., 2002)
mouse: active (Esler et al., 2002)
PhysiologyDeficiency of presenilin 1 decreases the production of amyloid beta-protein, indicating that presenilin is either itself the gamma-secretase of Alzheimer"s amyloidosis, or possibly functions as an obligatory cofactor for the gamma-secretase (Kimberly et al., 2000). There is also evidence that presenilin is responsible for proteolytic cleavage of the C-terminal intracellular protein Notch1 (Berezovska et al., 2000), although there has been some controversy over this (Kulic et al., 2000).
KnockoutConditional double knockout mice lacking presenilin 1 and presenilin 2 show impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration (Saura et al., 2004). A report or premature differentiation of neurons in presenilin 1-deficient mice (Handler et al., 2000) has been questioned (Wen et al., 2004).
Pharmaceutical relevancePresenilin 1 is an essential component of the gamma-secretase of Alzheimer"s disease, and as such is a drug target (Beher et al., 2003). Inhibitors of gamma-secretase inhibitors might also be of therapeutic benefit in colorectal neoplastic disease (van Es et al., 2005).
Pathways KEGGAlzheimer's disease
KEGGNotch signaling pathway
KEGGWnt signaling pathway
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Presenilin_1
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patternv/vgl/-/alScissile bondvl/lai/l/- (based on 16 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 2 3 0 2 0 0 1 0
Pro 0 0 0 0 0 0 0 0
Ala 2 2 2 4 2 4 0 2
Val 5 4 3 2 6 1 3 3
Leu 3 3 3 4 3 5 5 2
Ile 0 1 1 1 1 3 2 3
Met 0 0 0 0 0 0 0 0
Phe 1 1 3 0 0 0 1 0
Tyr 1 0 0 0 0 1 1 1
Trp 0 0 0 0 0 0 0 0
Ser 1 0 0 0 0 0 0 2
Thr 0 2 1 2 2 1 1 0
Cys 0 0 2 0 0 0 0 1
Asn 0 0 0 0 0 0 0 0
Gln 0 0 0 0 0 0 1 0
Asp 0 0 0 0 0 0 0 0
Glu 0 0 0 0 1 0 0 0
Lys 0 0 1 0 0 0 0 0
Arg 1 0 0 1 1 1 1 2
His 0 0 0 0 0 0 0 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
PSEN1 14q24.3 ENSG00000080815 5663 PSEN1 104311
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Psen1 12:D3 ENSMUSG00000019969 19164 MGI:1202717