CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004250
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Insulin-degrading enzyme 
Protein Synonyms/Alias
 Abeta-degrading protease; Insulin protease; Insulinase; Insulysin 
Gene Name
 IDE 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
192AVDSEHEKNVMNDAWacetylation[1]
192AVDSEHEKNVMNDAWubiquitination[2, 3, 4, 5, 6, 7, 8]
206WRLFQLEKATGNPKHubiquitination[3, 8]
223SKFGTGNKYTLETRPubiquitination[5]
308LYKIVPIKDIRNLYVacetylation[9]
308LYKIVPIKDIRNLYVubiquitination[2, 5, 7, 8, 10]
425NAVAFRFKDKERPRGacetylation[9]
511AIPDEVIKKWQNADLubiquitination[6]
527GKFKLPTKNEFIPTNubiquitination[5]
542FEILPLEKEATPYPAubiquitination[3, 6]
558IKDTAMSKLWFKQDDubiquitination[5, 8]
657ATFEIDEKRFEIIKEubiquitination[3]
697MTEVAWTKDELKEALubiquitination[3]
713DVTLPRLKAFIPQLLubiquitination[5]
826CFNTLRTKEQLGYIVubiquitination[5, 8, 11]
854RFIIQSEKPPHYLESubiquitination[5]
884MTEEAFQKHIQALAIubiquitination[2, 5, 7]
929NTEVAYLKTLTKEDIubiquitination[2, 3, 4, 6, 7]
933AYLKTLTKEDIIKFYubiquitination[5]
938LTKEDIIKFYKEMLAubiquitination[2, 7]
1018HINFMAAKL******ubiquitination[2, 6, 7, 10]
Reference
 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [11] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 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. 
Sequence Annotation
 NP_BIND 895 901 ATP (By similarity).
 REGION 336 342 Substrate binding exosite.
 REGION 359 363 Substrate binding.
 MOTIF 853 858 SlyX motif.
 ACT_SITE 111 111 Proton acceptor (By similarity).
 METAL 108 108 Zinc (By similarity).
 METAL 112 112 Zinc (By similarity).
 METAL 189 189 Zinc (By similarity).
 BINDING 429 429 ATP (By similarity).  
Keyword
 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Hydrolase; Membrane; Metal-binding; Metalloprotease; Nucleotide-binding; Polymorphism; Protease; Reference proteome; Secreted; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1019 AA 
Protein Sequence
MRYRLAWLLH PALPSTFRSV LGARLPPPER LCGFQKKTYS KMNNPAIKRI GNHITKSPED 60
KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP PNIAGLSHFC EHMLFLGTKK 120
YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLFDESCKD 180
REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVRQE 240
LLKFHSAYYS SNLMAVCVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ 300
LYKIVPIKDI RNLYVTFPIP DLQKYYKSNP GHYLGHLIGH EGPGSLLSEL KSKGWVNTLV 360
GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV 420
AFRFKDKERP RGYTSKIAGI LHYYPLEEVL TAEYLLEEFR PDLIEMVLDK LRPENVRVAI 480
VSKSFEGKTD RTEEWYGTQY KQEAIPDEVI KKWQNADLNG KFKLPTKNEF IPTNFEILPL 540
EKEATPYPAL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 600
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKIIEKMA TFEIDEKRFE 660
IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL 720
SRLHIEALLH GNITKQAALG IMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ 780
QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA 840
NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKSIEDMTEE AFQKHIQALA IRRLDKPKKL 900
SAECAKYWGE IISQQYNFDR DNTEVAYLKT LTKEDIIKFY KEMLAVDAPR RHKVSVHVLA 960
REMDSCPVVG EFPCQNDINL SQAPALPQPE VIQNMTEFKR GLPLFPLVKP HINFMAAKL 1019 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0031597; C:cytosolic proteasome complex; IEA:Compara.
 GO:0005615; C:extracellular space; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005782; C:peroxisomal matrix; IEA:Compara.
 GO:0005777; C:peroxisome; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0016887; F:ATPase activity; IEA:Compara.
 GO:0001540; F:beta-amyloid binding; IEA:Compara.
 GO:0031626; F:beta-endorphin binding; IEA:Compara.
 GO:0043559; F:insulin binding; IDA:UniProtKB.
 GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0050435; P:beta-amyloid metabolic process; IDA:UniProtKB.
 GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB.
 GO:0008340; P:determination of adult lifespan; IDA:UniProtKB.
 GO:0042447; P:hormone catabolic process; IEA:Compara.
 GO:1901143; P:insulin catabolic process; IDA:UniProtKB.
 GO:0008286; P:insulin receptor signaling pathway; NAS:UniProtKB.
 GO:0045861; P:negative regulation of proteolysis; IEA:Compara.
 GO:0032461; P:positive regulation of protein oligomerization; IDA:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
 GO:0051289; P:protein homotetramerization; IEA:Compara.
 GO:0051603; P:proteolysis involved in cellular protein catabolic process; IDA:UniProtKB.
 GO:0010992; P:ubiquitin homeostasis; IDA:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011249; Metalloenz_LuxS/M16.
 IPR011237; Pept_M16_dom.
 IPR011765; Pept_M16_N.
 IPR001431; Pept_M16_Zn_BS.
 IPR007863; Peptidase_M16_C. 
Pfam
 PF00675; Peptidase_M16
 PF05193; Peptidase_M16_C 
SMART
  
PROSITE
 PS00143; INSULINASE 
PRINTS