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
- FunctionsATP 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 bindingProcessesbeta-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 homeostasisComponentscell 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
Resource Link UniProtKB ID P14735 UniProtKB Entry Name IDE_HUMAN GenBank Protein ID 184556 GenBank Gene ID M21188 GenAtlas ID IDE HGNC ID HGNC:5381 - General References
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- 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]
- 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]
- 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. [Article]
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- 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. [Article]
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- Malito E, Ralat LA, Manolopoulou M, Tsay JL, Wadlington NL, Tang WJ: Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme. Biochemistry. 2008 Dec 2;47(48):12822-34. doi: 10.1021/bi801192h. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00626 Bacitracin approved, vet_approved yes inhibitor Details DB14487 Zinc acetate approved, investigational unknown ligand Details DB14533 Zinc chloride approved, investigational unknown cofactor Details DB00030 Insulin human approved, investigational unknown substratecleavage Details DB14548 Zinc sulfate, unspecified form approved, experimental unknown cofactor Details DB00071 Insulin pork approved unknown substrate Details DB09456 Insulin beef approved unknown substrate Details DB00046 Insulin lispro approved unknown substrate Details DB01307 Insulin detemir approved no substrate Details DB09564 Insulin degludec approved no substrate Details