Cloned (Comment) | Organism |
---|---|
genotyping, IDE shows a large genetic variability | Mus musculus |
genotyping, IDE shows a large genetic variability | Homo sapiens |
genotyping, IDE shows a large genetic variability | Rattus norvegicus |
Crystallization (Comment) | Organism |
---|---|
IDE in closed conformation | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | IDE knockout mice show decreased insulin degradation and associated hyperinsulinemia | Mus musculus |
additional information | silencing of IDE in Hep-Ge cells by siRNA inhibits insulin degradation by up to 76% | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1,10-phenanthroline | - |
Homo sapiens | |
1,10-phenanthroline | - |
Mus musculus | |
1,10-phenanthroline | - |
Rattus norvegicus | |
ATP | interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state | Homo sapiens | |
ATP | interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state | Mus musculus | |
ATP | interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state | Rattus norvegicus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0001 | - |
Insulin | pH not specified in the publication, temperature not specified in the publication | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cell surface | - |
Mus musculus | 9986 | - |
cell surface | - |
Rattus norvegicus | 9986 | - |
cytosol | mainly | Mus musculus | 5829 | - |
cytosol | mainly | Rattus norvegicus | 5829 | - |
endosome | - |
Mus musculus | 5768 | - |
endosome | - |
Rattus norvegicus | 5768 | - |
extracellular | secreted | Mus musculus | - |
- |
extracellular | secreted | Rattus norvegicus | - |
- |
mitochondrion | - |
Mus musculus | 5739 | - |
mitochondrion | - |
Rattus norvegicus | 5739 | - |
peroxisome | - |
Mus musculus | 5777 | - |
peroxisome | - |
Rattus norvegicus | 5777 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | dependent on | Mus musculus | |
Zn2+ | dependent on | Homo sapiens | |
Zn2+ | dependent on | Rattus norvegicus |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
110000 | - |
- |
Mus musculus |
110000 | - |
- |
Homo sapiens |
110000 | - |
- |
Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
amylin + H2O | Homo sapiens | - |
amylin peptide fragments | - |
? | |
glucagon + H2O | Homo sapiens | - |
glucagon peptide fragments | - |
? | |
insulin + H2O | Mus musculus | - |
insulin peptide fragments | - |
? | |
insulin + H2O | Rattus norvegicus | - |
insulin peptide fragments | - |
? | |
insulin + H2O | Homo sapiens | rapid degradation into inactive peptide fragments | insulin peptide fragments | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
adipose tissue | - |
Rattus norvegicus | - |
adrenal gland | - |
Rattus norvegicus | - |
brain | - |
Rattus norvegicus | - |
heart | - |
Rattus norvegicus | - |
kidney | - |
Rattus norvegicus | - |
liver | - |
Rattus norvegicus | - |
lung | - |
Rattus norvegicus | - |
additional information | IDE activity levels in decreasing order in liver, pancreas, kidney, testis, adrenal gland, spleen, ovary, lung, heart, muscle, brain, and adipose tissue | Rattus norvegicus | - |
muscle | - |
Rattus norvegicus | - |
ovary | - |
Rattus norvegicus | - |
pancreas | - |
Rattus norvegicus | - |
spleen | - |
Rattus norvegicus | - |
testis | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
amylin + H2O | - |
Homo sapiens | amylin peptide fragments | - |
? | |
glucagon + H2O | - |
Homo sapiens | glucagon peptide fragments | - |
? | |
insulin + H2O | - |
Mus musculus | insulin peptide fragments | - |
? | |
insulin + H2O | - |
Rattus norvegicus | insulin peptide fragments | - |
? | |
insulin + H2O | rapid degradation into inactive peptide fragments | Homo sapiens | insulin peptide fragments | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? | |
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 | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | the two domains of the monomer form a crypt to enclose the substrate and prevent entry or escape of the substrates | Mus musculus |
More | the two domains of the monomer form a crypt to enclose the substrate and prevent entry or escape of the substrates | Homo sapiens |
More | the two domains of the monomer form a crypt to enclose the substrate and prevent entry or escape of the substrates | Rattus norvegicus |
oligomer | monomeric IDE is composed of two domains, N- and C-terminal domain, of about 55000 Da, can occur as tetramer or dimer | Mus musculus |
oligomer | monomeric IDE is composed of two domains, N- and C-terminal domain, of about 55000 Da, can occur as tetramer or dimer | Homo sapiens |
oligomer | monomeric IDE is composed of two domains, N- and C-terminal domain, of about 55000 Da, can occur as tetramer or dimer | Rattus norvegicus |
Synonyms | Comment | Organism |
---|---|---|
IDE | - |
Mus musculus |
IDE | - |
Homo sapiens |
IDE | - |
Rattus norvegicus |
Insulin-degrading enzyme | - |
Mus musculus |
Insulin-degrading enzyme | - |
Homo sapiens |
Insulin-degrading enzyme | - |
Rattus norvegicus |
Insulinase | - |
Mus musculus |
Insulinase | - |
Homo sapiens |
Insulinase | - |
Rattus norvegicus |
More | IDE belongs to the family of cryptidases | Mus musculus |
More | IDE belongs to the family of cryptidases | Homo sapiens |
More | IDE belongs to the family of cryptidases | Rattus norvegicus |
General Information | Comment | Organism |
---|---|---|
malfunction | susceptibility of Goto-Kakizaki rats to diabetes due to IDE polymorphisms | Rattus norvegicus |
physiological function | IDE is important in maintaining insulin levels | Mus musculus |
physiological function | IDE is important in maintaining insulin levels and in insulin catabolism | Rattus norvegicus |
physiological function | IDE is important in maintaining insulin levels. IDE is involved in Alzheimer's disease, diabetes, and cardiovascular disease via oxidation and nitrosylation of IDE in oxidative stress. Reduced IDE activity, e.g. due to genetic dysfunction, leads to hyperinsulinemia and type 2 diabetes mellitus | Homo sapiens |