Q9JHR7 · IDE_MOUSE

  • Protein
    Insulin-degrading enzyme
  • Gene
    Ide
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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:12634421, PubMed:12732730, PubMed:24847884, PubMed:26394692, PubMed:9830016).
Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (By similarity).
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 (PubMed:24847884, PubMed:26394692).
Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (PubMed:9830016).
Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (By similarity).
Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (By similarity).
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

Miscellaneous

ATP-binding induces a conformation change.

Catalytic activity

  • Degradation of insulin, glucagon and other polypeptides. No action on proteins.
    EC:3.4.24.56 (UniProtKB | ENZYME | Rhea)

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Activity regulation

Activated by ATP, other nucleotide triphosphates and small peptides. Inhibited by bacitracin.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site108Zn2+ (UniProtKB | ChEBI)
Active site111Proton acceptor
Binding site112Zn2+ (UniProtKB | ChEBI)
Binding site189Zn2+ (UniProtKB | ChEBI)
Binding site359-363substrate
Binding site429ATP (UniProtKB | ChEBI)
Binding site895-901ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcell surface
Cellular Componentcytosol
Cellular Componentcytosolic proteasome complex
Cellular Componentendosome lumen
Cellular Componentextracellular exosome
Cellular Componentextracellular space
Cellular Componentmitochondrion
Cellular Componentperoxisomal matrix
Cellular Componentplasma membrane
Molecular Functionamyloid-beta binding
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functionbeta-endorphin binding
Molecular Functionendopeptidase activity
Molecular Functionidentical protein binding
Molecular Functioninsulin binding
Molecular Functionmetalloendopeptidase activity
Molecular Functionpeptide hormone binding
Molecular Functionprotein homodimerization activity
Molecular Functionprotein-containing complex binding
Molecular Functionzinc ion binding
Biological Processamyloid-beta clearance
Biological Processamyloid-beta clearance by cellular catabolic process
Biological Processamyloid-beta metabolic process
Biological Processantigen processing and presentation of endogenous peptide antigen via MHC class I
Biological Processbradykinin catabolic process
Biological Processhormone catabolic process
Biological Processinsulin catabolic process
Biological Processinsulin receptor recycling
Biological Processnegative regulation of proteolysis
Biological Processpeptide catabolic process
Biological Processprotein catabolic process
Biological Processproteolysis involved in protein catabolic process
Biological Processresponse to oxidative stress

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Insulin-degrading enzyme
  • EC number
  • Alternative names
    • Insulin protease (Insulinase)
    • Insulysin

Gene names

    • Name
      Ide

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9JHR7

Proteomes

Organism-specific databases

Phenotypes & Variants

Disruption phenotype

No visible phenotype, but mice display impaired degradation of insulin and APP-derived peptides (PubMed:12634421, PubMed:12732730).
At 17 to 20 weeks after birth, mutant mice display increased serum insulin levels and decreased glucose tolerance (PubMed:12634421).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis853-858Marked decrease in secretion.

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000744051-1019Insulin-degrading enzyme
Modified residue192N6-succinyllysine
Modified residue697N6-succinyllysine

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in brain and liver (at protein level) (PubMed:12634421, PubMed:12732730).
Detected in liver (PubMed:12732730).

Induction

Expression oscillates diurnally.

Interaction

Subunit

Homodimer. Can also form homotetramers.

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif853-858SlyX motif

Domain

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

Sequence similarities

Belongs to the peptidase M16 family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,019
  • Mass (Da)
    117,772
  • Last updated
    2000-10-01 v1
  • Checksum
    9443A6886110BE86
MRNGLVWLLHPALPGTLRSILGARPPPAKRLCGFPKQTYSTMSNPAIQRIEDQIVKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIPGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLLDASCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVREELLKFHSTYYSSNLMAICVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLRQLYKIVPIKDIRNLYVTFPIPDLQQYYKSNPGYYLGHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGKLHYYPLNGVLTAEYLLEEFRPDLIDMVLDKLRPENVRVAIVSKSFEGKTDRTEQWYGTQYKQEAIPEDVIQKWQNADLNGKFKLPTKNEFIPTNFEILSLEKDATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKRYNDKQPILLKKITEKMATFEIDKKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGVMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQQRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITMEKAIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGEIISQQYNYDRDNIEVAYLKTLTKDDIIRFYQEMLAVDAPRRHKVSVHVLAREMDSCPVVGEFPSQNDINLSEAPPLPQPEVIHNMTEFKRGLPLFPLVKPHINFMAAKL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
Q8CGB9Q8CGB9_MOUSEIde1019

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ278422
EMBL· GenBank· DDBJ
CAC01233.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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