Insulin-degrading enzyme

Details

Name
Insulin-degrading enzyme
Synonyms
  • 3.4.24.56
  • Abeta-degrading protease
  • Insulin protease
  • Insulinase
  • Insulysin
Gene Name
IDE
Organism
Humans
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
ATP binding / ATPase activity / beta-amyloid binding / beta-endorphin binding / glycoprotein binding / insulin binding / metalloendopeptidase activity / peptide binding / protein homodimerization activity / receptor binding / ubiquitin binding / virus receptor activity / zinc ion binding
Processes
beta-amyloid metabolic process / bradykinin catabolic process / determination of adult lifespan / hormone catabolic process / insulin catabolic process / insulin metabolic process / insulin receptor signaling pathway / negative regulation of proteolysis / positive regulation of protein oligomerization / protein heterooligomerization / protein homooligomerization / protein homotetramerization / protein processing / proteolysis / proteolysis involved in cellular protein catabolic process / ubiquitin homeostasis
Components
cell surface / cytoplasm / cytosol / cytosolic proteasome complex / extracellular space / mitochondrion / nucleoplasm / nucleus / peroxisomal matrix / peroxisome / plasma membrane
General Function
Zinc ion binding
Specific Function
Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
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-q25
External Identifiers
ResourceLink
UniProtKB IDP14735
UniProtKB Entry NameIDE_HUMAN
GenBank Protein ID184556
GenBank Gene IDM21188
GenAtlas IDIDE
HGNC IDHGNC:5381
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. [PubMed:3059494]
  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. [PubMed:2293021]
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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. [PubMed:10684867]
  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. [PubMed:17055432]
  8. Li Q, Krogmann T, Ali MA, Tang WJ, Cohen JI: The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for binding to insulin-degrading enzyme, a VZV receptor. J Virol. 2007 Aug;81(16):8525-32. Epub 2007 Jun 6. [PubMed:17553876]
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  10. Shen Y, Joachimiak A, Rosner MR, Tang WJ: Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature. 2006 Oct 19;443(7113):870-4. Epub 2006 Oct 11. [PubMed:17051221]
  11. Im H, Manolopoulou M, Malito E, Shen Y, Zhao J, Neant-Fery M, Sun CY, Meredith SC, Sisodia SS, Leissring MA, Tang WJ: Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE. J Biol Chem. 2007 Aug 31;282(35):25453-63. Epub 2007 Jul 5. [PubMed:17613531]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00071Insulin PorkapprovedunknownDetails
DB00626Bacitracinapproved, vet_approvedyesinhibitorDetails
DB01593Zincapproved, investigationalunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails
DB00030Insulin Humanapproved, investigationalunknownDetails