Hmdb loader
Survey
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP10019
Secondary Accession Numbers
  • 15958
Name Insulin-degrading enzyme
Synonyms
  1. Abeta-degrading protease
  2. Insulin protease
  3. Insulinase
  4. Insulysin
Gene Name IDE
Protein Type Enzyme
Biological Properties
General Function Involved in catalytic activity
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
Pathways Not Available
Reactions Not Available
GO Classification
Function
endopeptidase activity
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
transition metal ion binding
zinc ion binding
metalloendopeptidase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Cytoplasm
  2. Cell surface
Gene Properties
Chromosome Location Chromosome:1
Locus 10q23-q25
SNPs IDE
Gene Sequence
>3060 bp
ATGCGGTACCGGCTAGCGTGGCTTCTGCACCCCGCACTGCCCAGCACCTTCCGCTCAGTC
CTCGGCGCCCGCCTGCCGCCTCCGGAGCGCCTGTGTGGTTTCCAAAAAAAGACTTACAGC
AAAATGAATAATCCAGCCATCAAGAGAATAGGAAATCACATTACCAAGTCTCCTGAAGAC
AAGCGAGAATATCGAGGGCTAGAGCTGGCCAATGGTATCAAAGTACTTCTTATGAGTGAT
CCCACCACGGATAAGTCATCAGCAGCACTTGATGTGCACATAGGTTCATTGTCGGATCCT
CCAAATATTGCTGGCTTAAGTCATTTTTGTGAACATATGCTTTTTTTGGGAACAAAGAAA
TACCCTAAAGAAAATGAATACAGCCAGTTTCTCAGTGAGCATGCAGGAAGTTCAAATGCC
TTTACTAGTGGAGAGCATACCAATTACTATTTTGATGTTTCTCATGAACACCTAGAAGGT
GCCCTAGACAGGTTTGCACAGTTTTTTCTGTGCCCCTTGTTCGATGAAAGTTGCAAAGAC
AGAGAGGTGAATGCAGTTGATTCAGAACATGAGAAGAATGTGATGAATGATGCCTGGAGA
CTCTTTCAATTGGAAAAAGCTACAGGGAATCCTAAACACCCCTTCAGTAAATTTGGGACA
GGTAACAAATATACTCTGGAGACTAGACCAAACCAAGAAGGCATTGATGTAAGACAAGAG
CTACTGAAATTCCATTCTGCTTACTATTCATCCAACTTAATGGCTGTTTGTGTTTTAGGT
CGAGAATCTTTAGATGACTTGACTAATCTGGTGGTAAAGTTATTTTCTGAAGTAGAGAAC
AAAAATGTTCCATTGCCAGAATTTCCTGAACACCCTTTCCAAGAAGAACATCTTAAACAA
CTTTACAAAATAGTACCCATTAAAGATATTAGGAATCTCTATGTGACATTTCCCATACCT
GACCTTCAGAAATACTACAAATCAAATCCTGGTCATTATCTTGGTCATCTCATTGGGCAT
GAAGGTCCTGGAAGTCTGTTATCAGAACTTAAGTCAAAGGGCTGGGTTAATACTCTTGTT
GGTGGGCAGAAGGAAGGAGCCCGAGGTTTTATGTTTTTTATCATTAATGTGGACTTGACC
GAGGAAGGATTATTACATGTTGAAGATATAATTTTGCACATGTTTCAATACATTCAGAAG
TTACGTGCAGAAGGACCTCAAGAATGGGTTTTCCAAGAGTGCAAGGACTTGAATGCTGTT
GCTTTTAGGTTTAAAGACAAAGAGAGGCCACGGGGCTATACATCTAAGATTGCAGGAATA
TTGCATTATTATCCCCTAGAAGAGGTGCTCACAGCGGAATATTTACTGGAAGAATTTAGA
CCTGACTTAATAGAGATGGTTCTCGATAAACTCAGACCAGAAAATGTCCGGGTTGCCATA
GTTTCTAAATCTTTTGAAGGAAAAACTGATCGCACAGAAGAGTGGTATGGAACCCAGTAC
AAACAAGAAGCTATACCGGATGAAGTCATCAAGAAATGGCAAAATGCTGACCTGAATGGG
AAATTTAAACTTCCTACAAAGAATGAATTTATTCCTACGAATTTTGAGATTTTACCGTTA
GAAAAAGAGGCGACACCATACCCTGCTCTTATTAAGGATACAGTCATGAGCAAACTTTGG
TTCAAACAAGATGATAAGAAAAAAAAGCCGAAGGCTTGTCTCAACTTTGAATTTTTCAGC
CCATTTGCTTATGTGGACCCCTTGCACTGTAACATGGCCTATTTGTACCTTGAGCTCCTC
AAAGACTCACTCAACGAGTATGCATATGCAGCAGAGCTAGCAGGCTTGAGCTATGATCTC
CAAAATACCATCTATGGGATGTATCTTTCAGTGAAAGGTTACAATGACAAGCAGCCAATT
TTACTAAAGAAGATTATTGAGAAAATGGCTACCTTTGAGATTGATGAAAAAAGATTTGAA
ATTATCAAAGAAGCATATATGCGATCTCTTAACAATTTCCGGGCTGAACAGCCTCACCAG
CATGCCATGTACTACCTCCGCTTGCTGATGACTGAAGTGGCCTGGACTAAAGATGAGTTA
AAAGAAGCTCTGGATGATGTAACCCTTCCTCGCCTTAAGGCCTTCATACCTCAGCTCCTG
TCACGGCTGCACATTGAAGCCCTTCTCCATGGAAACATAACAAAGCAGGCTGCATTAGGA
ATTATGCAGATGGTTGAAGACACCCTCATTGAACATGCTCATACCAAACCTCTCCTTCCA
AGTCAGCTGGTTCGGTATAGAGAAGTTCAGCTCCCTGACAGAGGATGGTTTGTTTATCAG
CAGAGAAATGAAGTTCACAATAACTGTGGCATCGAGATATACTACCAAACAGACATGCAA
AGCACCTCAGAGAATATGTTTCTGGAGCTCTTCTGTCAGATTATCTCGGAACCTTGCTTC
AACACCCTGCGCACCAAGGAGCAGTTGGGCTATATCGTCTTCAGCGGGCCACGTCGAGCT
AATGGCATACAGAGCTTGAGATTCATCATCCAGTCAGAAAAGCCACCTCACTACCTAGAA
AGCAGAGTGGAAGCTTTCTTAATTACCATGGAAAAGTCCATAGAGGACATGACAGAAGAG
GCCTTCCAAAAACACATTCAGGCATTAGCAATTCGTCGACTAGACAAACCAAAGAAGCTA
TCTGCTGAGTGTGCTAAATACTGGGGAGAAATCATCTCCCAGCAATATAATTTTGACAGA
GATAACACTGAGGTTGCATATTTAAAGACACTTACCAAGGAAGATATCATCAAATTCTAC
AAGGAAATGTTGGCAGTAGATGCTCCAAGGAGACATAAGGTATCCGTCCATGTTCTTGCC
AGGGAAATGGATTCTTGTCCTGTTGTTGGAGAGTTCCCATGTCAAAATGACATAAATTTG
TCACAAGCACCAGCCTTGCCACAACCTGAAGTGATTCAGAACATGACCGAATTCAAGCGT
GGTCTGCCACTGTTTCCCCTTGTGAAACCACATATTAACTTCATGGCTGCAAAACTCTGA
Protein Properties
Number of Residues 1019
Molecular Weight 117967.5
Theoretical pI 6.59
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Insulin-degrading enzyme
MRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPED
KREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKK
YPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDESCKD
REVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVRQE
LLKFHSAYYSSNLMAVCVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQ
LYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWVNTLV
GGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAV
AFRFKDKERPRGYTSKIAGILHYYPLEEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAI
VSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFEILPL
EKEATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELL
KDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKGYNDKQPILLKKIIEKMATFEIDEKRFE
IIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLL
SRLHIEALLHGNITKQAALGIMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQ
QRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRA
NGIQGLRFIIQSEKPPHYLESRVEAFLITMEKSIEDMTEEAFQKHIQALAIRRLDKPKKL
SAECAKYWGEIISQQYNFDRDNTEVAYLKTLTKEDIIKFYKEMLAVDAPRRHKVSVHVLA
REMDSCPVVGEFPCQNDINLSQAPALPQPEVIQNMTEFKRGLPLFPLVKPHINFMAAKL
GenBank ID Protein 184556
UniProtKB/Swiss-Prot ID P14735
UniProtKB/Swiss-Prot Entry Name IDE_HUMAN
PDB IDs Not Available
GenBank Gene ID M21188
GeneCard ID IDE
GenAtlas ID IDE
HGNC ID HGNC:5381
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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. [PubMed:18986166 ]