3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH + H2O fluorogenic substrate derived from the reported Abeta1-40 core peptide cleavage sequence. The R183Q mutant enzyme exhibits significantly decreased rate of fluorogenic peptide hydrolysis, yet retains similar binding affinity by comparison with the wild-type enzyme Homo sapiens ? - ? 449100 3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O bradykinin mimetic substrate V Homo sapiens ? - ? 419677 3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH + H2O - Homo sapiens ? - ? 449102 3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK(2,4-dinitrophenyl)-OH + H2O - Homo sapiens ? - ? 449103 3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O - Homo sapiens ? - ? 394104 3.4.24.56 (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH + H2O - Homo sapiens ? - ? 449104 3.4.24.56 2-amino-benzoyl-GGFLRKAGQ-ethylenediamine-2,4-dinitrophenyl + H2O - Rattus norvegicus ? - ? 367388 3.4.24.56 2-amino-benzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O - Rattus norvegicus ? - ? 367387 3.4.24.56 2-amino-benzoyl-GGFLRKMGQ-ethylenediamine-2,4-dinitrophenyl + H2O - Rattus norvegicus ? - ? 367389 3.4.24.56 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O - Mus musculus ? - ? 383660 3.4.24.56 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O - Rattus norvegicus ? - ? 383660 3.4.24.56 2-aminobenzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O - Mus musculus 2-aminobenzoyl-GGFLR + KHGQ-ethylenediamine-2,4-dinitrophenyl - ? 403438 3.4.24.56 7-methoxycoumarin-4-yl-acetyl-RPPGF-SAFK-2,4-dinitrophenyl + H2O - Homo sapiens ? - ? 433343 3.4.24.56 7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O - Homo sapiens ? - ? 411432 3.4.24.56 7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O fluorogenic bradykinin-mimetic IDE substrate V Homo sapiens ? - ? 411432 3.4.24.56 7-methoxycoumarin-4-ylacetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O - Homo sapiens ? - ? 404102 3.4.24.56 Abeta42 + H2O - Homo sapiens ? - ? 448415 3.4.24.56 Abz-GFLRKGVQ-EDDnp + H2O - Rattus norvegicus ? - ? 411453 3.4.24.56 Abz-GGFLRKHGQ-EDDnp + H2O - Rattus norvegicus Abz-GGFLR + KHGQ-EDDnp - ? 394198 3.4.24.56 Abz-GGFLRKHGQ-EDDnp + H2O synthetic fluorogenic substrate Rattus norvegicus Abz-GGFLR + KHGQ-EDDnp - ? 394198 3.4.24.56 Abz-GGFLRKHGQ-EDDnp + H2O substrate or small peptide activation occurs through a cis effect Homo sapiens Abz-GGFLR + KHGQ-EDDnp - ? 394198 3.4.24.56 Abz-GGFLRKHGQ-EDDnp + H2O - Homo sapiens ? - ? 449441 3.4.24.56 Abz-Gly-Gly-Leu-Arg-Lys-His-Gly-Gln-EDDnp + H2O - Rattus norvegicus ? - ? 449445 3.4.24.56 Abz-SEKKDNYIIKGV-nitroY-OH + H2O a substrate based on the polypeptide sequence of the yeast P2 a-factor mating propheromone Rattus norvegicus ? - ? 411508 3.4.24.56 amylin + H2O - Homo sapiens ? - ? 367378 3.4.24.56 amylin + H2O - Rattus norvegicus ? - ? 367378 3.4.24.56 amylin + H2O degradation Mus musculus ? - ? 367378 3.4.24.56 amylin + H2O degradation Homo sapiens ? - ? 367378 3.4.24.56 amylin + H2O degradation Rattus norvegicus ? - ? 367378 3.4.24.56 amylin + H2O - Homo sapiens amylin peptide fragments - ? 410722 3.4.24.56 amylin + H2O identification of cleavage sites by mass spectrometry and NMR. The presence of a disulfide bond in amylin allows IDE to cut at an additional site in the middle of the peptide, amino acids 18-19, binding structure, overview Homo sapiens amylin peptide fragments - ? 410722 3.4.24.56 amyloid alpha-peptide + H2O - Homo sapiens ? - ? 432661 3.4.24.56 amyloid beta + H2O - Homo sapiens amyloid beta peptide fragments - ? 410723 3.4.24.56 amyloid beta + H2O - Rattus norvegicus amyloid beta peptide fragments - ? 410723 3.4.24.56 amyloid beta + H2O - Homo sapiens ? - ? 431588 3.4.24.56 amyloid beta + H2O role of insulin-degrading enzyme in the intracytosolic clearance of amyloid beta and other amyloid-like peptides Homo sapiens ? - ? 431588 3.4.24.56 amyloid beta peptide + H2O - Mus musculus ? - ? 367390 3.4.24.56 amyloid beta peptide + H2O - Homo sapiens ? - ? 367390 3.4.24.56 amyloid beta peptide + H2O - Rattus norvegicus ? - ? 367390 3.4.24.56 amyloid beta peptide + H2O the catalytic mechanisms for the hydrolysis of the three different peptide bonds (Lys28-Gly29, Phe19-Phe20, and His14-Gln15) of amyloid beta peptide is determined: For all these peptides, the nature of the substrate is found to influence the structure of the active enzyme-substrate complex. (1) activation of the metal-bound water molecule, (2) formation of the gem-diol intermediate, and (3) cleavage of the peptide bond. The process of water activation is found to be the rate-determining step for all three substrates Homo sapiens ? - ? 367390 3.4.24.56 amyloid beta peptide 1-40 + H2O physiolgical substrate Rattus norvegicus ? - ? 367391 3.4.24.56 amyloid beta-peptide (Abeta1-40) + H2O recombinant R183Q mutant enzyme is less active than the recombinant wild-type enzyme against recombinant amyloid beta-peptide (Abeta1-40) Homo sapiens ? - ? 449558 3.4.24.56 amyloid beta-peptide + H2O - Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O - Mus musculus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation Mus musculus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation Rattus norvegicus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation, amyloid beta-peptide is the key component of Alzheimer disease-associated senile plaques, genetic linkage and association of Alzheimer disease on chromosome 10q23-24 in the region harboring the IDE gene, chromosome 10-linked Alzheimer disease families show decreased enzyme activity, overview Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation, role for insulysin in regulating amyloid beta peptide levels in the brain Mus musculus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation, role for insulysin in regulating amyloid beta peptide levels in the brain Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O degradation, role for insulysin in regulating amyloid beta peptide levels in the brain Rattus norvegicus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O IDE is involved in clearance of amyloid-beta pepetide in the brain, enzyme deficiency may participate in the progression of Alzheimer's disease Mus musculus ? - ? 384178 3.4.24.56 amyloid beta-peptide + H2O activation in trans is observed with extended substrates that occupy both the active and distal sites Homo sapiens ? - ? 384178 3.4.24.56 amyloid beta-peptide 1-40 + H2O - Rattus norvegicus ? - ? 393934 3.4.24.56 amyloid beta-peptide 1-40 + H2O - Homo sapiens ? cleavage occurs at peptide bonds Phe19-Phe20, Phe20-Ala21, and Leu34-Met35, with the latter cleavage site being the initial and principal one ? 393934 3.4.24.56 amyloid beta-peptide 1-40 + H2O 76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP Rattus norvegicus ? - ? 393934 3.4.24.56 amyloid beta-peptide 1-42 + H2O - Homo sapiens ? cleavage occurs at peptide bonds Phe19-Phe20, Phe20-Ala21, and Leu34-Met35, with the latter cleavage site being the initial and principal one ? 433417 3.4.24.56 amyloid beta-peptide(1-40) + H2O - Rattus norvegicus ? - ? 449559 3.4.24.56 amyloid beta-peptide1-40 + H2O degradation Homo sapiens ? - ? 394230 3.4.24.56 amyloid beta-protein + H2O - Homo sapiens ? - ? 36859 3.4.24.56 amyloid beta-protein + H2O - Rattus norvegicus ? - ? 36859 3.4.24.56 amyloid beta-protein A21G + H2O Flemish genetic variant Homo sapiens ? - ? 384180 3.4.24.56 amyloid beta-protein E22K + H2O Italian genetic variant Homo sapiens ? - ? 384181 3.4.24.56 amyloid beta-protein E22Q + H2O Dutch genetic variant Homo sapiens ? - ? 384182 3.4.24.56 amyloid beta1-40 + H2O - Homo sapiens ? - ? 404307 3.4.24.56 amyloid beta40 + H2O - Rattus norvegicus amyloid beta40 peptide fragments - ? 410724 3.4.24.56 amyloid beta40 + H2O Abeta40, an Alzheimer amyloid beta peptide Homo sapiens amyloid beta40 peptide fragments - ? 410724 3.4.24.56 amyloid beta40 + H2O an Alzheimer amyloid beta peptide Homo sapiens amyloid beta40 peptide fragments - ? 410724 3.4.24.56 amyloid beta42 + H2O Abeta42, an Alzheimer amyloid beta peptide Homo sapiens amyloid beta42 peptide fragments - ? 410725 3.4.24.56 amyloid beta42 + H2O an Alzheimer amyloid beta peptide Homo sapiens amyloid beta42 peptide fragments - ? 410725 3.4.24.56 amyloid peptide + H2O 23 amino acid peptide resulting from internal proteolysis of wild-type type 2 transmembrane protein BRI2 Rattus norvegicus ? - ? 384183 3.4.24.56 amyloid peptide ABri + H2O 34 amino acid peptide resulting from internal proteolysis of genetically defect type 2 transmembrane protein BRI2 in patients with familial British dementia. Enzymic degradation of peptide is more efficient with monomeric peptide than with aggregated peptide Rattus norvegicus ? - ? 384187 3.4.24.56 amyloid peptide ADan + H2O 34 amino acid peptide resulting from internal proteolysis of genetically defect type 2 transmembrane protein BRI2 in patients with familial Danish dementia Rattus norvegicus ? - ? 384188 3.4.24.56 amyloid-beta + H2O activity is driven by the dynamic equilibrium between Abeta monomers and higher ordered aggregates. Met35-Val36 is a cleavage site in the amyloid-beta sequence. Amyloid-beta fragments resulting from cleavage by insulin-degrading enzyme form non-toxic amorphous aggregates Homo sapiens ? - ? 365809 3.4.24.56 amyloid-beta + H2O amyloid-beta monomers, either alone in solution or in dynamic equilibrium with higher aggregates, are cleaved at multiple sites by activity of insulin-degrading enzyme. Met35-Val36 is a cleavage site in the amyloid-beta sequence. Amyloid-beta fragments resulting from cleavage by insulin-degrading enzyme form non-toxic amorphous aggregates Homo sapiens ? - ? 365809 3.4.24.56 amyloid-beta peptide + H2O - Rattus norvegicus ? - ? 367380 3.4.24.56 amyloid-beta peptide + H2O - Mus musculus ? - ? 367380 3.4.24.56 angiotensin + H2O - Rattus norvegicus ? - ? 16268 3.4.24.56 ATP + H2O insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE Rattus norvegicus ADP + phosphate - ? 92967 3.4.24.56 ATP + H2O the enzyme contains one ATP binding site per enzyme molecule Rattus norvegicus ADP + phosphate - ? 92967 3.4.24.56 Atrial natriuretic factor + H2O - Drosophila melanogaster ? - ? 17182 3.4.24.56 Atrial natriuretic factor + H2O - Mammalia ? - ? 17182 3.4.24.56 Atrial natriuretic factor + H2O - Homo sapiens ? - ? 17182 3.4.24.56 Atrial natriuretic factor + H2O - Rattus norvegicus ? - ? 17182 3.4.24.56 atrial natriuretic peptide + H2O - Homo sapiens ? - ? 367383 3.4.24.56 ATTO 655-Cys-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Trp + H2O - Homo sapiens ? - ? 433491 3.4.24.56 beta-amyloid (Abeta)1-40 + H2O - Homo sapiens ? - ? 449676 3.4.24.56 beta-amyloid peptide + H2O - Rattus norvegicus ? - ? 367379 3.4.24.56 beta-amyloid precursor protein intracellular domain + H2O - Rattus norvegicus ? - ? 367386 3.4.24.56 beta-amyloid protein + H2O - Homo sapiens ? - ? 367382 3.4.24.56 beta-amyloid protein + H2O - Rattus norvegicus ? - ? 367382 3.4.24.56 beta-endorphin + H2O - Homo sapiens gamma-endorphin + ? - ? 367381 3.4.24.56 beta-endorphin + H2O - Rattus norvegicus gamma-endorphin + ? - ? 367381 3.4.24.56 beta-endorphin + H2O - Mus musculus gamma-endorphin + ? - ? 367381 3.4.24.56 beta-endorphin + H2O - Homo sapiens ? - ? 367385 3.4.24.56 beta-endorphin + H2O - Rattus norvegicus ? - ? 367385 3.4.24.56 beta-endorphin + H2O 76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP Rattus norvegicus ? - ? 367385 3.4.24.56 bradykinin + H2O - Rattus norvegicus ? - ? 16889 3.4.24.56 bradykinin + H2O - Homo sapiens ? - ? 16889 3.4.24.56 bradykinin + H2O cleavage at Pro/Phe site Homo sapiens ? - ? 16889 3.4.24.56 calcitonin + H2O - Homo sapiens ? - ? 367384 3.4.24.56 CH3NH-Ala-Ala-Ala-CONHCH3 + H2O energetic profile of proteolysis mechanism of IDE Homo sapiens ? - ? 411863 3.4.24.56 CH3NH-Leu-Tyr-Leu-CONHCH3 + H2O energetic profile of proteolysis mechanism of IDE Homo sapiens ? - ? 411864 3.4.24.56 Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2 + H2O fluorogenic derivative of amyloid beta containing residues 10-25 Homo sapiens ? - ? 404937 3.4.24.56 desalanine-insulin + H2O - Rattus norvegicus ? - ? 453287 3.4.24.56 desdipeptide-proinsulin + H2O - Rattus norvegicus ? - ? 453288 3.4.24.56 desnonapeptide-proinsulin + H2O - Rattus norvegicus ? - ? 453289 3.4.24.56 destridecapeptide-proinsulin + H2O - Rattus norvegicus ? - ? 453290 3.4.24.56 dynorphin A-17 + H2O - Rattus norvegicus ? - ? 367394 3.4.24.56 dynorphin B-13 + H2O - Rattus norvegicus ? - ? 367393 3.4.24.56 dynorphin B-9 + H2O - Rattus norvegicus ? - ? 367392 3.4.24.56 dynorphin B9 + H2O - Rattus norvegicus ? - ? 449884 3.4.24.56 epidermal growth factor + H2O identification of cleavage sites by mass spectrometry and NMR Homo sapiens epidermal growth factor peptide fragments - ? 410811 3.4.24.56 Fragment of cytochrome c + H2O Ile81-Glu108 Sus scrofa Hydrolyzed fragment of cytochrome c cleavage at Tyr97-Leu98 bond ? 17187 3.4.24.56 Glucagon + H2O - Drosophila melanogaster Hydrolyzed glucagon - ? 15306 3.4.24.56 Glucagon + H2O - Mammalia Hydrolyzed glucagon - ? 15306 3.4.24.56 Glucagon + H2O - Homo sapiens Hydrolyzed glucagon - ? 15306 3.4.24.56 Glucagon + H2O - Rattus norvegicus Hydrolyzed glucagon - ? 15306 3.4.24.56 Glucagon + H2O - Sus scrofa Hydrolyzed glucagon - ? 15306 3.4.24.56 Glucagon + H2O - Rattus norvegicus Hydrolyzed glucagon appearance of: tyrosine, leucine, lysine, alanine and phenylalanine ? 15306 3.4.24.56 Glucagon + H2O - Homo sapiens ? - ? 15578 3.4.24.56 Glucagon + H2O - Rattus norvegicus ? - ? 15578 3.4.24.56 Glucagon + H2O degradation Homo sapiens ? - ? 15578 3.4.24.56 Glucagon + H2O the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin Homo sapiens ? - ? 15578 3.4.24.56 glucagon + H2O - Homo sapiens glucagon peptide fragments - ? 410847 3.4.24.56 haemoglobin + H2O damaged haemoglobin oxidatively degraded Homo sapiens ? - ? 65404 3.4.24.56 InsL3 + H2O - Rattus norvegicus InsL3 fragments - ? 410864 3.4.24.56 InsL3 + H2O human substrate, degradation Rattus norvegicus InsL3 fragments - ? 410864 3.4.24.56 Insulin + H2O - Cavia porcellus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Drosophila melanogaster Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Mammalia Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Homo sapiens Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Sus scrofa Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Oryctolagus cuniculus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Canis lupus familiaris Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O - Frog Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O bovine Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O porcine Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O much better degradation than insulin growth factor II Homo sapiens Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O not: individual A and B-chains of insulin Drosophila melanogaster Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O not: individual A and B-chains of insulin Sus scrofa Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O Drosophila and rat enzyme cleave the A-chain of intact insulin between residues A13-A14 and A14-A15 Drosophila melanogaster Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O Drosophila and rat enzyme cleave the A-chain of intact insulin between residues A13-A14 and A14-A15 Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O degradation of 4 monoiodoinsulin isomers Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O the Drosophila enzyme cleaves the B-chain of intact insulin at B10-B11, B14-B15, B16-B17 and B25-B26 Drosophila melanogaster Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O equine Drosophila melanogaster Hydrolyzed insulin - ? 17169 3.4.24.56 Insulin + H2O specific for insulin Homo sapiens Hydrolyzed insulin degradation products are smaller than the A-chain of insulin ? 17169 3.4.24.56 Insulin + H2O specific for insulin Rattus norvegicus Hydrolyzed insulin stepwise degradation occurs in vivo, an early step in the process is the cleavage of the B-chain at Tyr16-Leu17 ? 17169 3.4.24.56 Insulin + H2O the insulin protease appears to first degrade insulin to multiple products with molecular sizes slightly smaller than insulin and subsequently to small peptides (e.g. containing tyrosine A-19) and amino acids (e.g. tyrosine A-14, B-16 and B-26) Rattus norvegicus Hydrolyzed insulin - ? 17169 3.4.24.56 insulin + H2O - Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O - Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O - Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O - Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O degradation Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O degradation Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O degradation Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O physiolgical substrate Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O stepwise degradation occurs in vivo, an early step in the process is the cleavage of the B-chain between Tyr16 and Leu17, that renders the molecule susceptible to further degradation by nonspecific proteases Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O seems to be implicated in insulin metabolism to terminate the response of cells to hormone, as well as in other biological functions, including muscle differentiation, regulation of growth factor levels and antigen processing Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O implicated in the process of membrane fusion and cell development Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O implicated in the process of membrane fusion and cell development Mammalia ? - ? 36836 3.4.24.56 insulin + H2O implicated in the process of membrane fusion and cell development Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O implicated in the process of membrane fusion and cell development Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O major route of insulin catabolism in body Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O insulin degradation Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O insulin degradation Mammalia ? - ? 36836 3.4.24.56 insulin + H2O insulin degradation Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O insulin degradation Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O the enzyme may play a general role in hormone metabolism and cellular regulation Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O the enzyme may play a general role in hormone metabolism and cellular regulation Mammalia ? - ? 36836 3.4.24.56 insulin + H2O the enzyme may play a general role in hormone metabolism and cellular regulation Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O the enzyme may play a general role in hormone metabolism and cellular regulation Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O important role in the metabolism of insulin Drosophila melanogaster ? - ? 36836 3.4.24.56 insulin + H2O degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O degradation, insulin occurs only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland are each insulin-negative, overview Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O degradation, insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O degradation, tissue-specific regulation, overview Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O degradation, type 2 diabetic GK rats exhibit defects in both insulin action and insulin degradation mainly due to mutation H18R and A890V in the insulysin protein Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O IDE is involved in the cellular insulin metabolism, insulin inhibits protein degradation via an interaction with IDE, regulation of protein degradation by insulin-degrading enzyme, overview Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O 76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O bovine substrate, degradation, identification of clevage sites in the alpha- and beta-chains, and of the produced proteolytic fragments by AP/MALDI-mass spectrometry, method evaluation, overview Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O porcine substrate, degradation Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O investigation of activity of IDE regarding cleavage site's preferentiality upon modification of environmental factors by atmospheric pressure/laser desorption ionization-mass spectrometry. The first insulin fragments produced by IDE are mainly [A (1-13) + B (1-9)], [A (1-14) + B (1-9)] and [A (1-14) + B (1-10)]. A second set of insulin fragments involving the C-terminal residues of the insulin A chain [A (14-21) and A (15-21)] and the fragments B (17-24) and B (17-25) are then produced, confirming a delayed action of IDE on these cleavage sites. A third set of insulin fragments at lower and higher m/z values start to appear soon after and their intensity increases as the intensity of the middle fragments intensity decreases Rattus norvegicus ? - ? 36836 3.4.24.56 insulin + H2O in HEK cells the enzyme has little impact on insulin clearance Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O the enzyme is implicated in proteolysis of insulin Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin Homo sapiens ? - ? 36836 3.4.24.56 insulin + H2O the enzyme plays a critical role in both the proteolytic degradation and inactivation of insulin Mus musculus ? - ? 36836 3.4.24.56 insulin + H2O - Rattus norvegicus insulin fragments - ? 410865 3.4.24.56 insulin + H2O degradation Rattus norvegicus insulin fragments - ? 410865 3.4.24.56 insulin + H2O - Mus musculus insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O - Homo sapiens insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O - Rattus norvegicus insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O - Xenopus laevis insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O high specificity Homo sapiens insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O high specificity Rattus norvegicus insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O cleavage of the B-chain Rattus norvegicus insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O rapid degradation into inactive peptide fragments Homo sapiens insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O IDE forms an enclosed catalytic chamber that completely engulfs and intimately interacts with a partially unfolded insulin molecule. The unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity for insulin, IDE-insulin binding structure and interaction analysis, overview Homo sapiens insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin Mus musculus insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin Homo sapiens insulin peptide fragments - ? 410866 3.4.24.56 insulin + H2O IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin Rattus norvegicus insulin peptide fragments - ? 410866 3.4.24.56 Insulin B-chain + H2O - Homo sapiens ? - ? 15728 3.4.24.56 Insulin B-chain + H2O - Rattus norvegicus ? - ? 15728 3.4.24.56 Insulin growth factor II + H2O - Drosophila melanogaster ? - ? 17181 3.4.24.56 Insulin growth factor II + H2O - Homo sapiens ? - ? 17181 3.4.24.56 insulin-like growth factor I + H2O - Homo sapiens insulin-like growth factor I peptide fragments - ? 410867 3.4.24.56 insulin-like growth factor I + H2O - Rattus norvegicus insulin-like growth factor I peptide fragments - ? 410867 3.4.24.56 insulin-like growth factor II + H2O - Homo sapiens insulin-like growth factor II peptide fragments - ? 410868 3.4.24.56 insulin-like growth factor II + H2O - Rattus norvegicus insulin-like growth factor II peptide fragments - ? 410868 3.4.24.56 insulin-like growth factor-II + H2O identification of cleavage sites by mass spectrometry and NMR Homo sapiens insulin-like growth factor-II peptide fragments - ? 410869 3.4.24.56 insulin-like peptide 3 + H2O IDE cleaves the peptide bond between R26 and W27 of the B-chain, and releases a pentapeptide, WSTEA, from the C-terminal of the B-chain Homo sapiens processed insulin-like peptide 3 + WSTEA - ? 410870 3.4.24.56 insulin-like peptide 3 + H2O IDE cleaves the peptide bond between R26 and W27 of the B-chain, and releases a pentapeptide, WSTEA, from the C-terminal of the B-chain, cleavage product identification by mass spectrometry, INSL-3 structure, overview Homo sapiens processed insulin-like peptide 3 + WSTEA - ? 410870 3.4.24.56 islet amyloid polypeptide + H2O degradation of islet amyloid polypeptide in beta-cells Mus musculus ? - ? 432824 3.4.24.56 islet amyloid polypeptide + H2O degradation of monomeric, but not oligomeric islet amyloid polypeptide in vitro Mus musculus ? - ? 432824 3.4.24.56 kallidin + H2O cleavage at Pro/Phe site Homo sapiens ? - ? 380633 3.4.24.56 Lysozyme + H2O degradation of oxidatively damaged lysozyme Homo sapiens ? - ? 16662 3.4.24.56 monoarginine-insulin + H2O - Rattus norvegicus ? - ? 453291 3.4.24.56 additional information - Rattus norvegicus ? - ? 89 3.4.24.56 additional information requirement for optimal substrate activity is the deblocking of the amino end of the A-chain Rattus norvegicus ? - ? 89 3.4.24.56 additional information fructose 1,6-bisphosphatase Homo sapiens ? - ? 89 3.4.24.56 additional information hexosephosphate isomerase Homo sapiens ? - ? 89 3.4.24.56 additional information aldolase Homo sapiens ? - ? 89 3.4.24.56 additional information the conserved glutamate in the zinc-binding site of human enzyme is a major catalytic residue, while a conserved cysteine in this region is not essential for catalysis Homo sapiens ? - ? 89 3.4.24.56 additional information preference for small substrates 2000-6000 MW Sus scrofa ? - ? 89 3.4.24.56 additional information insulin-like growth factor I Drosophila melanogaster ? - ? 89 3.4.24.56 additional information human growth hormone is not appreciably degraded Rattus norvegicus ? - ? 89 3.4.24.56 additional information no inactivation of: lactate dehydrogenase Homo sapiens ? - ? 89 3.4.24.56 additional information thyroid-stimulating hormone Homo sapiens ? - ? 89 3.4.24.56 additional information prolactin Homo sapiens ? - ? 89 3.4.24.56 additional information hexokinase Homo sapiens ? - ? 89 3.4.24.56 additional information not: growth hormone Homo sapiens ? - ? 89 3.4.24.56 additional information does not act on glucagon-like peptide 1, nerve growth factor, somatostatin, bradykinin, vasopressin, platelet-derived growth factor, and vasoactive intestinal peptide, proinsulin, epidermal growth factor and IGF-I bind to the enzyme but are not efficiently degraded Homo sapiens ? - ? 89 3.4.24.56 additional information EGF and insulin C-peptide are no substrates Rattus norvegicus ? - ? 89 3.4.24.56 additional information gamma-endorphin, Leu-Arg, and Leu-enkephalin are not significantly cleaved Rattus norvegicus ? - ? 89 3.4.24.56 additional information enzyme can degrade cleaved mitochondrial targeting sequences, role of enzyme within mitochondria Homo sapiens ? - ? 89 3.4.24.56 additional information enzyme may participate in prostatic and uterine growth Rattus norvegicus ? - ? 89 3.4.24.56 additional information hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview Mus musculus ? - ? 89 3.4.24.56 additional information hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview Rattus norvegicus ? - ? 89 3.4.24.56 additional information hyperinsulinemia is probably elevated through insulin's competitition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview Homo sapiens ? - ? 89 3.4.24.56 additional information membrane-bound, but not cytosolic, enzyme selectively decreases during hippocampal development from mild cognitive impairment to mild to severe Alzheimer's disease, overview Homo sapiens ? - ? 89 3.4.24.56 additional information no association of IDE haplotypes with the risk of dementia, IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimer’s disease Homo sapiens ? - ? 89 3.4.24.56 additional information regulation of enzyme expression in the liver, overview Homo sapiens ? - ? 89 3.4.24.56 additional information the human enzyme interacts with Varicella-zoster virus glycoprotein E, gE, facilitating viral infection and cell-to-cell spread of the virus, and thus serving as a cellular receptor for the virus, the binding region of the viral protein is located at amino acids 32 to 71 of gE, deletion of this sequence leads to loss of binding ability, overview, the secondary structure of the IDE binding domain is likely important for its interaction with IDE Homo sapiens ? - ? 89 3.4.24.56 additional information the insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population, overview Homo sapiens ? - ? 89 3.4.24.56 additional information IDE has a preference for basic or hydrophobic amino acids at the carboxyl side of cleavage sites, overview, the catalytic domain of IDE is located in the amino subunit Homo sapiens ? - ? 89 3.4.24.56 additional information the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH Mus musculus ? - ? 89 3.4.24.56 additional information the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH Homo sapiens ? - ? 89 3.4.24.56 additional information the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH Rattus norvegicus ? - ? 89 3.4.24.56 additional information IDE interacts with vimentin and nestin, vimentin binds IDE with a higher affinity than nestin in vitro. A nestin tail fragment interacts with insulin-degrading enzyme in Xenopus egg extracts, overview. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview Xenopus laevis ? - ? 89 3.4.24.56 additional information IDE interacts with vimentin and with nestin during mitosis, vimentin binds IDE with a higher affinity than nestin in vitro. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview Rattus norvegicus ? - ? 89 3.4.24.56 additional information IDE is a neutral thiol metalloprotease Homo sapiens ? - ? 89 3.4.24.56 additional information IDE is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid beta, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor-II and transforming growth factor-alpha, TGF-alpha, over IGF-I and epidermal growth factor, respectively. IDE cleaves its substrates at multiple sites in a biased stochastic manner Homo sapiens ? - ? 89 3.4.24.56 additional information active site structure of IDE, overview. Interactions of the two full-length Alzheimer amyloid beta peptides, Abeta40 and Abeta42, with the fully active form of IDE through unrestrained, all-atom molecular dynamics simulations, using free and small fragment-bound, Asp1-Glu3 and Lys16-Asp23 of Abeta40 and Asp1-Glu3 and Lys16-Glu22 of Abeta42, mutated forms of IDE and NMR structures of the full-length Abeta40 and Abeta42, overview. In comparison to Abeta40, Abeta42 is more flexible and interacts through a smaller number, 17-22, of hydrogen bonds in the catalytic chamber of IDE. Both the substrates adopt more beta-sheet character in the IDE environment. Hydrogen bonding interactions between IDE and substrates amyloidbeta40 and amyloidbeta42, overview Homo sapiens ? - ? 89 3.4.24.56 additional information IDE shows catalytic activity toward two peptides of different length, simulating a portion of B chain of insulin, analysis by density functional theory method and the hybrid exchange-correlation functional B3LYP in gas phase and in the protein environment, modelling, reaction mechanism, overview. The proteolysis reaction is exothermic and proceeds quickly as the barrier in the rate-limiting step falls widely within the range of values expected for an enzymatic catalysis Homo sapiens ? - ? 89 3.4.24.56 additional information the putative ATP-binding domain is a key modulator of IDE proteolytic activity Homo sapiens ? - ? 89 3.4.24.56 additional information the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. IDE is an allosteric enzyme Mus musculus ? - ? 89 3.4.24.56 additional information the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. Regulatory mechanism, overview. IDE is an allosteric enzyme Rattus norvegicus ? - ? 89 3.4.24.56 additional information the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. Tyr831 is also involved in substrate positioning, enzyme-substrate interactions required for the regulation of the enzyme with open and closed stages, mechanism, overview. The closed stage in absence of substrate is unstable. IDE is an allosteric enzyme Homo sapiens ? - ? 89 3.4.24.56 additional information the enzyme selectively degrades biologically important substrates associated with type 2 diabetes and Alzheimer's disease Homo sapiens ? - ? 89 3.4.24.56 additional information a functional requirement for active site residues F115, A140, F141, Y150, W199, F202, F820, and Y831 is established, and specific contributions of residue charge, size, and hydrophobicity to substrate binding, specificity, and proteolysis are demonstrated Homo sapiens ? - ? 89 3.4.24.56 o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O - Homo sapiens ? - ? 394461 3.4.24.56 Oxidatively damaged hemoglobin + H2O - Drosophila melanogaster ? - ? 17184 3.4.24.56 Oxidatively damaged hemoglobin + H2O - Mammalia ? - ? 17184 3.4.24.56 Oxidatively damaged hemoglobin + H2O - Homo sapiens ? - ? 17184 3.4.24.56 Oxidatively damaged hemoglobin + H2O - Rattus norvegicus ? - ? 17184 3.4.24.56 peptide containing the mitochondrial targeting sequence of E1alpha subunit of human pyruvate dehydrogenase + H2O hydrolysis occurs at several sites Homo sapiens ? - ? 385516 3.4.24.56 peptide V + H2O a bradykinin-mimetic fluorogenic peptide substrate V Homo sapiens ? - ? 412669 3.4.24.56 peptide V + H2O a bradykinin-mimetic fluorogenic peptide substrate V Rattus norvegicus ? - ? 412669 3.4.24.56 peptide V + H2O a bradykinin-mimetic fluorogenic peptide substrate V Xenopus laevis ? - ? 412669 3.4.24.56 Porcine proinsulin intermediates + H2O cleaved proinsulin, desdipeptide-proinsulin, desnonapeptide-proinsulin, destridecapeptide-proinsulin, desalanine-insulin, monoarginine-insulin and diarginine-proinsulin are degraded at 19.8%, 25.6%, 63.5%, 73.7%, 101.5%, 98% and 98% of the activity of insulin, respectively Rattus norvegicus ? - ? 17185 3.4.24.56 Proinsulin + H2O 15fold greater rate of insulin destruction over that for proinsulin Rattus norvegicus Hydrolyzed proinsulin - ? 17179 3.4.24.56 protein ANP + H2O - Homo sapiens ? - ? 421229 3.4.24.56 protein BNP + H2O - Homo sapiens ? - ? 421230 3.4.24.56 protein CNP + H2O - Homo sapiens ? - ? 421231 3.4.24.56 protein DNP + H2O - Homo sapiens ? - ? 421232 3.4.24.56 reduced amylin + H2O identification of cleavage sites by mass spectrometry Homo sapiens reduced amylin peptide fragments - ? 410985 3.4.24.56 relaxin + H2O - Rattus norvegicus relaxin fragments - ? 410986 3.4.24.56 relaxin + H2O procine substrate, degradation Rattus norvegicus relaxin fragments - ? 410986 3.4.24.56 relaxin-3 + H2O - Rattus norvegicus relaxin-3 fragments - ? 410987 3.4.24.56 relaxin-3 + H2O human substrate, degradation Rattus norvegicus relaxin-3 fragments - ? 410987 3.4.24.56 somatostatin + H2O cleavage at Phe6-Phe7 bond Homo sapiens ? - ? 366788 3.4.24.56 somatostatin + H2O somatostatin in addition to being a substrate, is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the catalytic cleft of the enzyme. One exosite, which displays high affinity for somatostatin, regulates only the interaction of insulin-degrading-enzyme with larger substrates (such as insulin and beta-amyloid1-40) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by the enzyme of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself), probably acts through the alteration of an open-closed equilibrium Homo sapiens ? - ? 366788 3.4.24.56 Transforming growth factor + H2O - Drosophila melanogaster ? - ? 17183 3.4.24.56 Transforming growth factor + H2O - Mammalia ? - ? 17183 3.4.24.56 Transforming growth factor + H2O - Homo sapiens ? - ? 17183 3.4.24.56 Transforming growth factor + H2O - Rattus norvegicus ? - ? 17183 3.4.24.56 transforming growth factor alpha + H2O - Homo sapiens ? - ? 355684 3.4.24.56 transforming growth factor-alpha + H2O identification of cleavage sites by mass spectrometry Homo sapiens transforming growth factor-alpha peptide fragments - ? 411036 3.4.24.56 Tryptic fragment of bovine serum albumin + H2O Leu503-Lys518 Sus scrofa Hydrolyzed tryptic fragment of bovine serum albumin cleaved at Phe506-His507 ? 17186 3.4.24.56 ubiquitin + H2O IDE cleaves ubiquitin in a biphasic manner, first, by rapidly removing the two C-terminal glycines (kcat = 2/sec) followed by a slow cleavage between residues 72-73 (kcat = 0.07/sec), thereby producing the inactive Ub1-74 and Ub1-72 Homo sapiens ? - ? 355649 3.4.24.56 urodilatin + H2O - Homo sapiens ? - ? 421693 3.4.24.56 [(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O - Homo sapiens [(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH - ir 450858 3.4.24.56 [(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O - Mus musculus [(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH - ir 450858