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Details on Person UniProt:P14735 IDE

Class:IdReferenceGeneProduct:57060
_chainChangeLogchain:1-1019 added on Fri February 6 2015
_displayNameUniProt:P14735 IDE
_timestamp2024-11-03 19:36:49
chainchain:1-1019
checksum8A28AEF75EDA0EDA
commentFUNCTION 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.FUNCTION (Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).CATALYTIC ACTIVITY Degradation of insulin, glucagon and other polypeptides. No action on proteins.COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Activated by small peptides (By similarity). Activated by ATP and GTP, and to a lesser extent by CTP, TTP and PPPi (PubMed:17613531). Inhibited by bacitracin (PubMed:17055432, PubMed:17613531). In vitro modification of Cys residues impairs enzyme activity (PubMed:18986166).SUBUNIT Homodimer (Probable) (PubMed:17051221, PubMed:19321446, PubMed:23922390, PubMed:26394692, PubMed:29596046). Can also form homotetramers (By similarity).SUBUNIT (Microbial infection) Interacts (via N-terminus) with varicella-zoster virus (VZV) envelope glycoprotein E (via N-terminus); the membrane-associated isoform may function as an entry receptor for this virus (PubMed:17055432, PubMed:17553876).INTERACTION Present at the cell surface of neuron cells. The membrane-associated isoform is approximately 5 kDa larger than the known cytosolic isoform.ALTERNATIVE PRODUCTS Detected in brain and in cerebrospinal fluid (at protein level).DOMAIN The SlyX motif may be involved in the non-conventional secretion of the protein.PTM The N-terminus is blocked.MISCELLANEOUS ATP-binding induces a conformation change.SIMILARITY Belongs to the peptidase M16 family.
descriptionrecommendedName: fullName evidence="22"Insulin-degrading enzyme ecNumber evidence="5 6 13 14"3.4.24.56 alternativeName: Abeta-degrading protease alternativeName: fullName evidence="22"Insulin protease shortName evidence="22"Insulinase alternativeName: fullName evidence="22"Insulysin
geneNameIDE
identifierP14735
isSequenceChangedFALSE
keyword3D-structure
Allosteric enzyme
Alternative splicing
ATP-binding
Cell membrane
Cytoplasm
Direct protein sequencing
Host cell receptor for virus entry
Host-virus interaction
Hydrolase
Membrane
Metal-binding
Metalloprotease
Nucleotide-binding
Protease
Proteomics identification
Receptor
Reference proteome
Secreted
Zinc
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
nameIDE
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8997751] ENSEMBL:ENSG00000119912 IDE [Homo sapiens]
secondaryIdentifierIDE_HUMAN
B2R721
B7ZAU2
D3DR35
Q5T5N2
sequenceLength1019
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8971483] UniProt:P14735-1 IDE [Homo sapiens]
[ReferenceIsoform:8971484] UniProt:P14735-2 IDE [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:5696861] IDE [mitochondrial outer membrane] [Homo sapiens]
[EntityWithAccessionedSequence:6783095] PolyUb-IDE [mitochondrial outer membrane] [Homo sapiens]
[EntityWithAccessionedSequence:9033133] IDE [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:9033157] IDE [peroxisomal matrix] [Homo sapiens]
[EntityWithAccessionedSequence:9794504] IDE [endosome lumen] [Homo sapiens]
(referenceSequence)[GroupModifiedResidue:6783191] ubiquitinylated lysine (PolyUb [mitochondrial outer membrane]) at unknown position
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No pathways have been reviewed or authored by UniProt:P14735 IDE (57060)