3.4.24.56: insulysin
This is an abbreviated version!
For detailed information about insulysin, go to the full flat file.
Word Map on EC 3.4.24.56
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3.4.24.56
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alzheimer
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neprilysin
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abeta
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hippocampus
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dementia
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mellitus
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cerebral
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morris
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amyloid-beta
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metalloprotease
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maze
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neuroprotective
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amyloidogenic
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tau
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beta-amyloid
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neurodegenerative
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presenilin
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endothelin-converting
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senile
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gamma-secretase
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beta-protein
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125i-insulin
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abeta-degrading
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hyperinsulinemia
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metalloendopeptidase
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bacitracin
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beta-secretase
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late-onset
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amylin
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microglia
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medicine
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adam10
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non-amyloidogenic
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glutathione-insulin
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enzyme-1
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b-chains
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analysis
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ad-like
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anti-ide
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exosite
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beta-peptide
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abeta1-40
- 3.4.24.56
- alzheimer
- neprilysin
- abeta
- hippocampus
- dementia
- mellitus
- cerebral
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morris
- amyloid-beta
- metalloprotease
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maze
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neuroprotective
-
amyloidogenic
- tau
- beta-amyloid
- neurodegenerative
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presenilin
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endothelin-converting
-
senile
- gamma-secretase
- beta-protein
- 125i-insulin
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abeta-degrading
- hyperinsulinemia
- metalloendopeptidase
- bacitracin
- beta-secretase
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late-onset
- amylin
- microglia
- medicine
- adam10
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non-amyloidogenic
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glutathione-insulin
- enzyme-1
- b-chains
- analysis
-
ad-like
-
anti-ide
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exosite
- beta-peptide
- abeta1-40
Reaction
Degradation of insulin, glucagon and other polypeptides. No action on proteins =
Synonyms
ADE, amyloid degrading enzyme, cgd6_5510, EC 3.4.22.11, EC 3.4.99.10, EC 3.4.99.45, gamma-endorphin-generating enzyme, IDE, INS20-19, insulin degrading enzyme, Insulin protease, Insulin proteinase, Insulin-degrading enzyme, Insulin-degrading neutral proteinase, Insulin-glucagon protease, Insulin-specific protease, Insulinase, Insulysin, Metalloinsulinase, More, pitrilysin metallopeptidase 1, Pitrm1
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3.4.24.56 insulysinAdvanced search results
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results (Natural Substrates Products
Natural Substrates Products on EC 3.4.24.56 - insulysin
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NATURAL SUBSTRATE 
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
amyloid beta + H2O
?
role of insulin-degrading enzyme in the intracytosolic clearance of amyloid beta and other amyloid-like peptides
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-
?
amyloid beta42 + H2O
amyloid beta42 peptide fragments
Abeta42, an Alzheimer amyloid beta peptide
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?
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
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?
ATP + H2O
ADP + phosphate
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insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
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?
epidermal growth factor + H2O
epidermal growth factor peptide fragments
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identification of cleavage sites by mass spectrometry and NMR
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?
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
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identification of cleavage sites by mass spectrometry and NMR
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?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
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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
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?
islet amyloid polypeptide + H2O
?
degradation of islet amyloid polypeptide in beta-cells
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?
reduced amylin + H2O
reduced amylin peptide fragments
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identification of cleavage sites by mass spectrometry
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?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
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identification of cleavage sites by mass spectrometry
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?
amylin + H2O
amylin peptide fragments
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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
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?
amyloid beta + H2O
amyloid beta peptide fragments
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?
amyloid beta-peptide + H2O
?
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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
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?
amyloid beta-peptide + H2O
?
degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase
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?
amyloid beta-peptide + H2O
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degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
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?
amyloid beta-peptide + H2O
?
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degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
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?
amyloid beta-peptide + H2O
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IDE is involved in clearance of amyloid-beta pepetide in the brain, enzyme deficiency may participate in the progression of Alzheimer's disease
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?
amyloid beta-peptide + H2O
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degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
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?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
Abeta40, an Alzheimer amyloid beta peptide
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?
Glucagon + H2O
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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
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?
insulin + H2O
?
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insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
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?
insulin + H2O
?
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implicated in the process of membrane fusion and cell development
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?
insulin + H2O
?
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the enzyme may play a general role in hormone metabolism and cellular regulation
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?
insulin + H2O
?
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insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
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?
insulin + H2O
?
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implicated in the process of membrane fusion and cell development
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?
insulin + H2O
?
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the enzyme may play a general role in hormone metabolism and cellular regulation
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?
insulin + H2O
?
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degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
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?
insulin + H2O
?
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degradation, insulin occurs only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland are each insulin-negative, overview
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?
insulin + H2O
?
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degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
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?
insulin + H2O
?
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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
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?
insulin + H2O
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in HEK cells the enzyme has little impact on insulin clearance
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?
insulin + H2O
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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
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?
insulin + H2O
?
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implicated in the process of membrane fusion and cell development
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?
insulin + H2O
?
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the enzyme may play a general role in hormone metabolism and cellular regulation
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?
insulin + H2O
?
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degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
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?
insulin + H2O
?
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degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
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?
insulin + H2O
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the enzyme plays a critical role in both the proteolytic degradation and inactivation of insulin
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?
insulin + H2O
?
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insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
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?
insulin + H2O
?
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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
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?
insulin + H2O
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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
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?
insulin + H2O
?
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implicated in the process of membrane fusion and cell development
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?
insulin + H2O
?
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the enzyme may play a general role in hormone metabolism and cellular regulation
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?
insulin + H2O
?
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degradation, insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
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?
insulin + H2O
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degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
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?
insulin + H2O
?
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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
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?
insulin + H2O
insulin peptide fragments
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?
insulin + H2O
insulin peptide fragments
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rapid degradation into inactive peptide fragments
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?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
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?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
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?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
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?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
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?
additional information
?
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enzyme can degrade cleaved mitochondrial targeting sequences, role of enzyme within mitochondria
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?
additional information
?
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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
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?
additional information
?
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membrane-bound, but not cytosolic, enzyme selectively decreases during hippocampal development from mild cognitive impairment to mild to severe Alzheimer's disease, overview
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?
additional information
?
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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 Alzheimers disease
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?
additional information
?
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regulation of enzyme expression in the liver, overview
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?
additional information
?
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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
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?
additional information
?
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the insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population, overview
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?
additional information
?
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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
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?
additional information
?
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the enzyme selectively degrades biologically important substrates associated with type 2 diabetes and Alzheimer's disease
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?
additional information
?
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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
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?
additional information
?
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enzyme may participate in prostatic and uterine growth
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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