Summary for peptidase M16.002: insulysin

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

 

Names
MEROPS Nameinsulysin
Other namesinsulinase, insulin-degrading enzyme, insulin protease
Domain architecture
MEROPS Classification
Classification Clan ME >> Subclan (none) >> Family M16 >> Subfamily A >> M16.002
Holotypeinsulysin (Homo sapiens), Uniprot accession P14735 (peptidase unit: 44-235), MERNUM MER0001214
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00221
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.24 (Metalloendopeptidases) >> Peptidase 3.4.24.56
EnzymologyBRENDA database
Proteolytic eventsCutDB database (9 cleavages)
Activity statushuman: active (Roth, 2004)
mouse: active (Saric et al., 1994)
PhysiologyMay contribute to intracellular degradation of insulin and other proteins. Genetic and in vitro evidence suggests that reduced activity of the enzyme may contribute to Alzheimer"s disease and type 2 diabetes mellitus (Farris et al., 2003).
KnockoutMice with homozygous deficiency of the gene have been characterised by Farris et al., 2003. They showed abnormally low catabolism of the Alzheimer"s A-beta peptide and insulin. Polymorphism may be associated with human type 2 diabetes (Karamohamed et al., 2003).
Pathways KEGGAlzheimer's disease
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Insulin_degrading_enzyme
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patternl/v/l/rScissile bondlfrg/-/-/- (based on 101 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 14 6 6 3 14 16 8 5
Pro 0 1 1 3 0 0 3 4
Ala 2 3 1 3 5 4 3 8
Val 4 22 9 3 2 6 4 8
Leu 32 4 37 6 21 7 8 5
Ile 1 0 1 0 0 5 2 3
Met 0 0 1 0 0 0 0 1
Phe 1 5 6 15 19 7 7 5
Tyr 3 2 1 4 4 5 5 1
Trp 0 0 0 0 0 1 0 0
Ser 2 8 9 6 2 7 6 3
Thr 0 5 4 2 0 3 3 1
Cys 8 10 4 5 2 1 3 4
Asn 1 0 5 0 0 1 1 1
Gln 3 2 3 4 3 4 3 0
Asp 3 1 2 4 0 0 2 6
Glu 7 3 4 3 0 1 6 7
Lys 2 4 2 4 4 6 3 3
Arg 8 19 1 29 15 23 3 5
His 8 6 4 7 8 2 2 1
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
IDE 10q23-q25 ENSG00000119912 3416 IDE 146680
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ide 19:C2 ENSMUSG00000024823 15925 MGI:96412