| IED ID | IndEnz0002015937 |
| Enzyme Type ID | protease015937 |
| Protein Name |
Insulin-degrading enzyme EC 3.4.24.56 Insulin protease Insulinase Insulysin |
| Gene Name | Ide |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MRNGLVWLLHPALPSTLHSILGARPPPVKRLCGFPKQIYSTMNNPAIQRIEDHIVKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIPGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDASCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVREELLKFHSTYYSSNLMAICVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQQYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGKLHYYPLNGVLTAEYLLEEFRPDLIDMVLDKLRPENVRVAIVSKSFEGKTDRTEQWYGTQYKQEAIPEDVIQKWQNADLNGKFKLPTKNEFIPTNFEILALEKDATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKGYNDKQPILLKKITEKMATFEIDKKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGVMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQRRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITMEKAIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGEIISQQYNYDRDNIEVAYLKTLSKDDIIKFYKEMLAVDAPRRHKVSVHVLAREMDSCPVVGEFPSQNDINLSEAPPLPQPEVIHNMTEFKRGLPLFPLVKPHINFMAAKL |
| Enzyme Length | 1019 |
| Uniprot Accession Number | P35559 |
| Absorption | |
| Active Site | ACT_SITE 111; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU10096 |
| Activity Regulation | ACTIVITY REGULATION: Activated by ATP, other nucleotide triphosphates and small peptides (PubMed:14527953, PubMed:21731629, PubMed:22049080). Inhibited by bacitracin (PubMed:12941771). {ECO:0000269|PubMed:12941771, ECO:0000269|PubMed:14527953, ECO:0000269|PubMed:21731629, ECO:0000269|PubMed:22049080}. |
| Binding Site | BINDING 429; /note="ATP"; /evidence="ECO:0000269|PubMed:22049080, ECO:0007744|PDB:3TUV" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Degradation of insulin, glucagon and other polypeptides. No action on proteins.; EC=3.4.24.56; Evidence={ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:1445854, ECO:0000269|PubMed:14527953, ECO:0000269|PubMed:1836994, ECO:0000269|PubMed:21731629, ECO:0000269|PubMed:22049080}; |
| DNA Binding | |
| EC Number | 3.4.24.56 |
| Enzyme 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:1836994, PubMed:1445854, PubMed:10684867, PubMed:12941771, PubMed:14527953, PubMed:22049080). 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 (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (PubMed:10684867). 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. {ECO:0000250|UniProtKB:P14735, ECO:0000250|UniProtKB:Q9JHR7, ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:12941771, ECO:0000269|PubMed:1445854, ECO:0000269|PubMed:14527953, ECO:0000269|PubMed:1836994, ECO:0000269|PubMed:22049080}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 895..901; /note="ATP"; /evidence="ECO:0000269|PubMed:22049080, ECO:0007744|PDB:3TUV" |
| Features | Active site (1); Beta strand (31); Binding site (1); Chain (1); Helix (44); Metal binding (3); Modified residue (2); Motif (1); Mutagenesis (10); Nucleotide binding (1); Region (1); Turn (6) |
| Keywords | 3D-structure;ATP-binding;Allosteric enzyme;Cell membrane;Cytoplasm;Direct protein sequencing;Hydrolase;Membrane;Metal-binding;Metalloprotease;Nucleotide-binding;Protease;Reference proteome;Secreted;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:1836994}. Cell membrane {ECO:0000269|PubMed:10684867}. Secreted {ECO:0000269|PubMed:10684867}. |
| Modified Residue | MOD_RES 192; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9JHR7; MOD_RES 697; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9JHR7 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 3P7L; 3P7O; 3TUV; |
| Mapped Pubmed ID | 10958757; 11235899; 15494400; 15749695; 15985623; 17259336; 18411275; 18941241; 19406747; 26576191; 28157092; 28447730; 28553348; 29940507; 29948724; 9000694; |
| Motif | MOTIF 853..858; /note=SlyX motif; /evidence=ECO:0000250|UniProtKB:Q9JHR7 |
| Gene Encoded By | |
| Mass | 117,710 |
| Kinetics | |
| Metal Binding | METAL 108; /note="Zinc"; /evidence="ECO:0000269|PubMed:21731629, ECO:0007744|PDB:3P7L"; METAL 112; /note="Zinc"; /evidence="ECO:0000269|PubMed:21731629, ECO:0007744|PDB:3P7L"; METAL 189; /note="Zinc"; /evidence="ECO:0000269|PubMed:21731629, ECO:0007744|PDB:3P7L" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.56; |