Insulin-degrading enzyme

Details

Name
Insulin-degrading enzyme
Synonyms
  • 3.4.24.56
  • Abeta-degrading protease
  • Insulin protease
  • Insulinase
  • Insulysin
Gene Name
IDE
UniProtKB Entry
P14735Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037135|Insulin-degrading enzyme
MRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPED
KREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKK
YPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDESCKD
REVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVRQE
LLKFHSAYYSSNLMAVCVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQ
LYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWVNTLV
GGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAV
AFRFKDKERPRGYTSKIAGILHYYPLEEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAI
VSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFEILPL
EKEATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELL
KDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKGYNDKQPILLKKIIEKMATFEIDEKRFE
IIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLL
SRLHIEALLHGNITKQAALGIMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQ
QRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRA
NGIQGLRFIIQSEKPPHYLESRVEAFLITMEKSIEDMTEEAFQKHIQALAIRRLDKPKKL
SAECAKYWGEIISQQYNFDRDNTEVAYLKTLTKEDIIKFYKEMLAVDAPRRHKVSVHVLA
REMDSCPVVGEFPCQNDINLSQAPALPQPEVIQNMTEFKRGLPLFPLVKPHINFMAAKL
Number of residues
1019
Molecular Weight
117967.49
Theoretical pI
6.74
GO Classification
Functions
endopeptidase activity / identical protein binding
Processes
amyloid-beta clearance / amyloid-beta clearance by cellular catabolic process / amyloid-beta metabolic process / antigen processing and presentation of endogenous peptide antigen via MHC class I / peptide catabolic process / positive regulation of protein binding / positive regulation of protein catabolic process / protein catabolic process / proteolysis involved in protein catabolic process / regulation of aerobic respiration / ubiquitin recycling
Components
basolateral plasma membrane / external side of plasma membrane / extracellular exosome
General 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: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
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytosol
Gene sequence
>lcl|BSEQ0016342|Insulin-degrading enzyme (IDE)
ATGAGCAAACTTTGGTTCAAACAAGATGATAAGTTTTTTTTGCCGAAGGCTTGTCTCAAC
TTTGAATTTTTCAGCCCATTTGCTTATGTGGACCCCTTGCACTGTAACATGGCCTATTTG
TACCTTGAGCTCCTCAAAGACTCACTCAACGAGTATGCATATGCAGCAGAGCTAGCAGGC
TTGAGCTATGATCTCCAAAATACCATCTATGGGATGTATCTTTCAGTGAAAGGTTACAAT
GACAAGCAGCCAATTTTACTAAAGAAGATTATTGAGAAAATGGCTACCTTTGAGATTGAT
GAAAAAAGATTTGAAATTATCAAAGAAGCATATATGCGATCTCTTAACAATTTCCGGGCT
GAACAGCCTCACCAGCATGCCATGTACTACCTCCGCTTGCTGATGACTGAAGTGGCCTGG
ACTAAAGATGAGTTAAAAGAAGCTCTGGATGATGTAACCCTTCCTCGCCTTAAGGCCTTC
ATACCTCAGCTCCTGTCACGGCTGCACATTGAAGCCCTTCTCCATGGAAACATAACAAAG
CAGGCTGCATTAGGAATTATGCAGATGGTTGAAGACACCCTCATTGAACATGCTCATACC
AAACCTCTCCTTCCAAGTCAGCTGGTTCGGTATAGAGAAGTTCAGCTCCCTGACAGAGGA
TGGTTTGTTTATCAGCAGAGAAATGAAGTTCACAATAACTGTGGCATCGAGATATACTAC
CAAACAGACATGCAAAGCACCTCAGAGAATATGTTTCTGGAGCTCTTCTGTCAGATTATC
TCGGAACCTTGCTTCAACACCCTGCGCACCAAGGAGCAGTTGGGCTATATCGTCTTCAGC
GGGCCACGTCGAGCTAATGGCATACAGGGCTTGAGATTCATCATCCAGTCAGAAAAGCCA
CCTCACTACCTAGAAAGCAGAGTGGAAGCTTTCTTAATTACCATGGAAAAGTCCATAGAG
GACATGACAGAAGAGGCCTTCCAAAAACACATTCAGGCATTAGCAATTCGTCGACTAGAC
AAACCAAAGAAGCTATCTGCTGAGTGTGCTAAATACTGGGGAGAAATCATCTCCCAGCAA
TATAATTTTGACAGAGATAACACTGAGGTTGCATATTTAAAGACACTTACCAAGGAAGAT
ATCATCAAATTCTACAAGGAAATGTTGGCAGTAGATGCTCCAAGGAGACATAAGGTATCC
GTCCATGTTCTTGCCAGGGAAATGGATTCTTGTCCTGTTGTTGGAGAGTTCCCATGTCAA
AATGACATAAATTTGTCACAAGCACCAGCCTTGCCACAACCTGAAGTGATTCAGAACATG
ACCGAATTCAAGCGTGGTCTGCCACTGTTTCCCCTTGTGAAACCACATATTAACTTCATG
GCTGCAAAACTCTGA
Chromosome Location
10
Locus
10q23.33
External Identifiers
ResourceLink
UniProtKB IDP14735
UniProtKB Entry NameIDE_HUMAN
GenBank Protein ID184556
GenBank Gene IDM21188
GeneCard IDIDE
GenAtlas IDIDE
HGNC IDHGNC:5381
PDB ID(s)2G47, 2G48, 2G49, 2G54, 2G56, 2JBU, 2JG4, 2WBY, 2WC0, 2WK3, 2YPU, 3CWW, 3E4A, 3E4Z, 3E50, 3H44, 3HGZ, 3N56, 3N57, 3OFI, 3QZ2, 4DTT, 4DWK, 4GS8, 4GSC, 4GSF, 4IFH, 4IOF, 4LTE, 4M1C, 4NXO, 4PES, 4PF7, 4PF9, 4PFC, 4QIA, 4RAL, 4RE9, 5CJO, 5UOE, 5WOB, 6B3Q, 6B70, 6B7Y, 6B7Z, 6BF6, 6BF7, 6BF8, 6BF9, 6BFC, 6BYZ, 6EDS, 6MQ3, 7K1D, 7K1E, 7K1F, 7RZE, 7RZF, 7RZG, 7RZH, 7RZI
KEGG IDhsa:3416
IUPHAR/Guide To Pharmacology ID2371
NCBI Gene ID3416
General References
  1. Affholter JA, Fried VA, Roth RA: Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III. Science. 1988 Dec 9;242(4884):1415-8. [Article]
  2. Affholter JA, Hsieh CL, Francke U, Roth RA: Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes. Mol Endocrinol. 1990 Aug;4(8):1125-35. [Article]
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  6. Vekrellis K, Ye Z, Qiu WQ, Walsh D, Hartley D, Chesneau V, Rosner MR, Selkoe DJ: Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci. 2000 Mar 1;20(5):1657-65. [Article]
  7. Li Q, Ali MA, Cohen JI: Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell. 2006 Oct 20;127(2):305-16. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Insulin-degrading enzyme (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Bacitracinapproved, vet_approvedyestargetinhibitorDetails
Zinc acetateapproved, investigationalunknownenzymeligandDetails
Zinc chlorideapproved, investigationalunknownenzymecofactorDetails
Insulin humanapproved, investigationalunknownenzymesubstratecleavageDetails
Zinc sulfate, unspecified formapproved, experimentalunknownenzymecofactorDetails
Insulin porkapprovedunknownenzymesubstrateDetails
Insulin beefapprovedunknownenzymesubstrateDetails
Insulin lisproapprovedunknownenzymesubstrateDetails
Insulin detemirapprovednoenzymesubstrateDetails
Insulin degludecapprovednoenzymesubstrateDetails
Insulin icodecapproved, investigationalnoenzymesubstrateDetails