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FLASH GENE
Symbol IDE contributors: mct/npt - updated : 12-10-2016
HGNC name insulin-degrading enzyme
HGNC id 5381
Location 10q23.33      Physical location : 94.211.440 - 94.333.852
Synonym name
  • insulinase
  • insulysin
  • insulin protease
  • Synonym symbol(s) INSULYSIN, FLJ35968
    EC.number 3.4.24.56
    DNA
    TYPE functioning gene
    STRUCTURE 120.25 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see IFIT1
    Physical map
    LOC119358 10q23.32 similar to Small nuclear ribonucleoprotein Sm D2 (snRNP core protein D2) (Sm-D2) HTR7 10q22-q24 5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled) RPP30 10q23.32-q23.33 ribonuclease P (30kD) ANKRD1 10q23.33 ankyrin repeat domain 1 (cardiac muscle) LOC387701 10 LOC387701 MGC34007 10q23.33 hypothetical protein MGC34007 MGC16202 10q23.33 hypothetical protein MGC16202 FLJ37306 10q23.32 hypothetical protein FLJ37306 LOC387702 10 similar to hypothetical protein FLJ25224 PPP1R3C 10q23-q24 protein phosphatase 1, regulatory (inhibitor) subunit 3C LOC389995 10 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) TNKS2 10q23.3 tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase 2 C10orf13 10q23.33 chromosome 10 open reading frame 13 BTAF1 10q22-q23 BTAF1 RNA polymerase II, B-TFIID transcription factor-associated, 170kDa (Mot1 homolog, S. cerevisiae) CPEB3 10q23.33 cytoplasmic polyadenylation element binding protein 3 FLJ20445 10q23.33 hypothetical protein FLJ20445 LOC389996 10 similar to MAP/microtubule affinity-regulating kinase 2 isoform a; ELKL motif kinase 1; ELKL motif kinase IDE 10q24 insulin-degrading enzyme KIF11 10q24.1 kinesin family member 11 LOC283014 10q23.33 similar to eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa; eukaryotic translation initiation factor 2, subunit 2 (beta, 38kD ); eukaryotic initiation factor 2-beta HHEX 10q24 hematopoietically expressed homeobox SEC15L1 10q23.33 SEC15-like 1 (S. cerevisiae) CYP26C1 10q23.33 cytochrome P450, family 26, subfamily C, polypeptide 1 CYP26A1 10q23-q24 cytochrome P450, family 26, subfamily A, polypeptide 1 LOC389997 10 similar to Saccharomyces cerevisiae Nip7p homolog LOC387703 10 similar to ATP-dependent DNA helicase II, 70 kDa subunit (Lupus Ku autoantigen protein p70) (Ku70) (70 kDa subunit of Ku antigen) (Thyroid-lupus autoantigen) (TLAA) (CTC box binding factor 75 kDa subunit) (CTCBF) (CTC75) LOC389998 10 similar to 60S ribosomal protein L17 (L23) FER1L3 10q23.3 fer-1-like 3, myoferlin (C. elegans) C10orf3 10q23.33 chromosome 10 open reading frame 3 GPR120 10q23.33 G protein-coupled receptor 120 RBP4 10q24 retinol binding protein 4, plasma PDE6C 10q24 phosphodiesterase 6C, cGMP-specific, cone, alpha prime C10orf4 10q23.33 chromosome 10 open reading frame 4 LGI1 10q24 leucine-rich, glioma inactivated 1 FLJ33990 10q23.33 hypothetical protein FLJ33990 PSMD4P2 10q23.33 proteasome (prosome, macropain) 26S subunit, non-ATPase, 4, pseudogene 2 PLCE1 10q23 phospholipase C, epsilon 1 AD24 10q23.33 AD24 protein KIAA0608 10q23.33 KIAA0608 protein HELLS 10q23-q24 helicase, lymphoid-specific CYP2C18 10q24 cytochrome P450, family 2, subfamily C, polypeptide 18 CYP2C19 10q24 cytochrome P450, family 2, subfamily C, polypeptide 19
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 5896 110 1018 widely Farris (2005)
  • also called 15a or variant 1
  • exon 15a
  • - - 4480 - 464 in brain and non-neural tissues Farris (2005)
  • also called 15b or variant 2
  • exon 15b
  • located in both cytosol and mitochondria
  • 15b-IDE can exist as a heterodimer with the 15a isoform or as a homodimer
  • decreased ability to degrade insulin and amyloid beta-protein
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuterus  highly
     male systemtestis  highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N terminal catalytic domain
  • a C terminus facilitating substrate recognition as well as playing a key role in the oligomerization of IDE
  • conjugated MetalloP
    mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • peptidase M16 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,cytosolic
    text zinc metalloprotease found in the cytosol of all cells (Carpenter 2010)
    basic FUNCTION
  • may play a role in the cellular processing of insulin
  • may be involved in intercellular peptide signaling
  • involved in the termination of the insulin response
  • involved in the clearance of insulin and amyloid-beta
  • acting as a zinc metalloprotease involved in the degradation of the amyloid beta-peptide (Carpenter 2010)
  • exhibits a remarkable specificity to degrade insulin without breaking the disulfide bonds that hold the insulin A and B chains together (Manolopoulou 2009)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complex with four substrates (insulin B chain, amyloid-beta peptide (1-40), amylin and glucagon)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • one zinc ion per subunit
  • protein
  • binds to the nonglycosylated precursor of varicella-zoster virus gE protein found in the endoplasmic reticulum (Carpenter 2010)
  • IAPP is also a known substrate of the protease insulin-degrading enzyme (IDE)
  • cell & other
    REGULATION
    inhibited by potently by physiologically relevant concentrations of S-nitrosylation and oxidation agents (Malito 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    reduction in MME and IDE activity is not the primary cause of APP accumulation in Alzheimer disease, but rather a late-stage phenomenon secondary to neurodegeneration
    Susceptibility to type 2 diabetes
    Variant & Polymorphism other
  • polymorphisms increasing the risk of type 2 diabetes
  • association of IDE polymorphisms with T2DM (Rudovich 2009)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    inhibition of IDE may represent an approach to improve glucose metabolism in human type 2 diabetes, without inducing amyloid deposition and its deleterious effects
    ANIMAL & CELL MODELS