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IDE

GeneName

IDE

Summary

IDE, also known as insulin degrading enzyme or insulin protease, is a 118 kDa metalloendopeptidase that is primarily localised to the cytoplasm, but can also be found at the cell surface and in various organelles including the mitochondrion and peroxisomes. It plays a crucial role in the catabolism of insulin and other peptides, facilitating the clearance of amyloid-beta, which is implicated in Alzheimer’s disease. IDE is involved in multiple biological processes such as hormone metabolism, proteolysis, and regulation of protein binding, highlighting its importance in cellular homeostasis and metabolic regulation.

Importance

IDE is relevant to: - The pathophysiology of Alzheimer’s disease through its role in amyloid-beta clearance and metabolism - Diabetes research due to its function in insulin degradation and metabolic regulation - Understanding protein catabolism and recycling mechanisms within cells - Potential therapeutic targets for diseases linked to protein misfolding and aggregation

Top Products

For researchers investigating the Insulin degrading enzyme (IDE), we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-Insulin degrading enzyme / IDE antibody (ab32216), which has garnered 96 citations, reflecting its strong reputation in the field. This antibody is validated for use in Western blotting (WB) and immunohistochemistry (IHC), making it a reliable choice for various applications. Additionally, we offer the recombinant antibody, Anti-Insulin degrading enzyme / IDE antibody [EPR6098(2)] (ab133561). This product is also validated for WB and IHC and has been cited 17 times, indicating its growing acceptance among researchers. Both antibodies have been validated in knockout models, ensuring their effectiveness in specific experimental contexts. These options provide researchers with the flexibility and reliability needed for studying IDE.

Abcam Product Citation Summary

The IDE antibody (ab32216) has been extensively used in various studies focusing on insulin clearance, TUDCA treatment effects, and the role of IDE in conditions such as allergies and Alzheimer's disease. The majority of the experiments were conducted using mouse models, particularly in liver and brain tissues, as well as in human HepG2 cells, indicating a strong interest in understanding IDE's function in metabolic processes and neurodegenerative conditions.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab32216
Mouse
WB
Liver, insulin clearance and activity
31156453
ab32216
Human
WB
HepG2 cells, TUDCA treatment
29093479
ab32216
Mouse
WB
Liver, TUDCA treatment effects on IDE expression
29093479
ab32216
Mouse
WB
Brain, allergy effects on IDE levels
23915208
ab32216
Human
WB
Human samples, allergy effects on IDE levels
23915208
ab32216
Mouse
WB
Brain, allergy effects on IDE levels
23915208
ab32216
Mouse
WB
Hippocampus and cortex
30110883
ab32216
Mouse
WB
Brain, Alzheimer's disease
33182586
ab32216
Mouse
WB
Mouse, theasaponin E1 effects on protein expression
32429462

Domain

The SlyX motif may be involved in the non-conventional secretion of the protein.

Function

Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling (PubMed:10684867, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:21098034, PubMed:2293021, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:26968463, PubMed:29596046). Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (PubMed:23922390, PubMed:26394692, PubMed:29596046). Contributes to the regulation of peptide hormone signaling cascades and regulation of blood glucose homeostasis via its role in the degradation of insulin, glucagon and IAPP (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (Probable) (PubMed:26394692, PubMed:9830016). Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (PubMed:21098034). Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (PubMed:21098034). Involved in antigen processing. Produces both the N terminus and the C terminus of MAGEA3-derived antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T lymphocytes by MHC class I.

(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).

Post-translational modifications

The N-terminus is blocked.

Sequence Similarities

Belongs to the peptidase M16 family.

Tissue Specificity

Detected in brain and in cerebrospinal fluid (at protein level).

Cellular localization

Alternative names

Insulin-degrading enzyme, Abeta-degrading protease, Insulin protease, Insulysin, Insulinase, IDE

swissprot:P14735 entrezGene:3416 omim:146680