Q9JHR7 · IDE_MOUSE
- ProteinInsulin-degrading enzyme
- GeneIde
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1019 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
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
Cofactor
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 108 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Active site | 111 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 112 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 189 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 359-363 | substrate | ||||
Sequence: LVGGQ | ||||||
Binding site | 429 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 895-901 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DKPKKLS |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameInsulin-degrading enzyme
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JHR7
Proteomes
Organism-specific databases
Subcellular Location
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 853-858 | Marked decrease in secretion. | ||||
Sequence: Missing |
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000074405 | 1-1019 | Insulin-degrading enzyme | |||
Sequence: MRNGLVWLLHPALPGTLRSILGARPPPAKRLCGFPKQTYSTMSNPAIQRIEDQIVKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIPGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLLDASCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVREELLKFHSTYYSSNLMAICVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLRQLYKIVPIKDIRNLYVTFPIPDLQQYYKSNPGYYLGHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGKLHYYPLNGVLTAEYLLEEFRPDLIDMVLDKLRPENVRVAIVSKSFEGKTDRTEQWYGTQYKQEAIPEDVIQKWQNADLNGKFKLPTKNEFIPTNFEILSLEKDATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKRYNDKQPILLKKITEKMATFEIDKKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGVMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQQRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITMEKAIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGEIISQQYNYDRDNIEVAYLKTLTKDDIIRFYQEMLAVDAPRRHKVSVHVLAREMDSCPVVGEFPSQNDINLSEAPPLPQPEVIHNMTEFKRGLPLFPLVKPHINFMAAKL | ||||||
Modified residue | 192 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 697 | N6-succinyllysine | ||||
Sequence: K |
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 853-858 | SlyX motif | ||||
Sequence: EKPPHY |
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 statusComplete
- Length1,019
- Mass (Da)117,772
- Last updated2000-10-01 v1
- Checksum9443A6886110BE86
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q8CGB9 | Q8CGB9_MOUSE | Ide | 1019 |
Keywords
- Technical term