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Protein

Insulin-degrading enzyme

Gene

Ide

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

Degradation of insulin, glucagon and other polypeptides. No action on proteins.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Activated by ATP, other nucleotide triphosphates and small peptides. Inhibited by bacitracin (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi108 – 1081ZincPROSITE-ProRule annotation
Active sitei111 – 1111Proton acceptorPROSITE-ProRule annotation
Metal bindingi112 – 1121ZincPROSITE-ProRule annotation
Metal bindingi189 – 1891ZincPROSITE-ProRule annotation
Binding sitei429 – 4291ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi895 – 9017ATPBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. glycoprotein binding Source: MGI
  3. insulin binding Source: MGI
  4. metalloendopeptidase activity Source: UniProtKB
  5. peptide binding Source: MGI
  6. protein homodimerization activity Source: MGI
  7. receptor binding Source: MGI
  8. ubiquitin binding Source: MGI
  9. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-amyloid metabolic process Source: UniProtKB
  2. bradykinin catabolic process Source: UniProtKB
  3. determination of adult lifespan Source: MGI
  4. insulin catabolic process Source: MGI
  5. insulin metabolic process Source: MGI
  6. positive regulation of protein oligomerization Source: MGI
  7. protein homooligomerization Source: MGI
  8. proteolysis Source: MGI
  9. proteolysis involved in cellular protein catabolic process Source: MGI
  10. ubiquitin homeostasis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Protein family/group databases

MEROPSiM16.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-degrading enzyme (EC:3.4.24.56)
Alternative name(s):
Insulin protease
Short name:
Insulinase
Insulysin
Gene namesi
Name:Ide
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:96412. Ide.

Subcellular locationi

Cytoplasm 1 Publication. Cell membrane 1 Publication. Secreted 1 Publication

GO - Cellular componenti

  1. cell surface Source: MGI
  2. cytoplasm Source: MGI
  3. cytosol Source: MGI
  4. extracellular space Source: MGI
  5. mitochondrion Source: MGI
  6. nucleoplasm Source: MGI
  7. peroxisome Source: MGI
  8. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi853 – 8586Missing : Marked decrease in secretion. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10191019Insulin-degrading enzymePRO_0000074405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei192 – 1921N6-succinyllysine1 Publication
Modified residuei697 – 6971N6-succinyllysine1 Publication

Proteomic databases

MaxQBiQ9JHR7.
PaxDbiQ9JHR7.
PRIDEiQ9JHR7.

PTM databases

PhosphoSiteiQ9JHR7.

Expressioni

Inductioni

Expression oscillates diurnally.1 Publication

Gene expression databases

CleanExiMM_IDE.
GenevestigatoriQ9JHR7.

Interactioni

Subunit structurei

Homodimer. Can form higher oligomers (By similarity).By similarity

Protein-protein interaction databases

DIPiDIP-60044N.

Structurei

3D structure databases

ProteinModelPortaliQ9JHR7.
SMRiQ9JHR7. Positions 42-1011.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi853 – 8586SlyX motif

Domaini

The SlyX motif may be involved in the non-conventional secretion of the protein.

Sequence similaritiesi

Belongs to the peptidase M16 family.Curated

Phylogenomic databases

eggNOGiCOG1025.
HOVERGENiHBG106799.
InParanoidiQ9JHR7.

Family and domain databases

Gene3Di3.30.830.10. 4 hits.
InterProiIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 4 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JHR7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRNGLVWLLH PALPGTLRSI LGARPPPAKR LCGFPKQTYS TMSNPAIQRI
60 70 80 90 100
EDQIVKSPED KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP
110 120 130 140 150
PNIPGLSHFC EHMLFLGTKK YPKENEYSQF LSEHAGSSNA FTSGEHTNYY
160 170 180 190 200
FDVSHEHLEG ALDRFAQFFL CPLLDASCKD REVNAVDSEH EKNVMNDAWR
210 220 230 240 250
LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE LLKFHSTYYS
260 270 280 290 300
SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLRQ
310 320 330 340 350
LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GYYLGHLIGH EGPGSLLSEL
360 370 380 390 400
KSKGWVNTLV GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK
410 420 430 440 450
LRAEGPQEWV FQECKDLNAV AFRFKDKERP RGYTSKIAGK LHYYPLNGVL
460 470 480 490 500
TAEYLLEEFR PDLIDMVLDK LRPENVRVAI VSKSFEGKTD RTEQWYGTQY
510 520 530 540 550
KQEAIPEDVI QKWQNADLNG KFKLPTKNEF IPTNFEILSL EKDATPYPAL
560 570 580 590 600
IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL
610 620 630 640 650
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKRYNDKQPI LLKKITEKMA
660 670 680 690 700
TFEIDKKRFE IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL
710 720 730 740 750
KEALDDVTLP RLKAFIPQLL SRLHIEALLH GNITKQAALG VMQMVEDTLI
760 770 780 790 800
EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ QRNEVHNNCG IEIYYQTDMQ
810 820 830 840 850
STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA NGIQGLRFII
860 870 880 890 900
QSEKPPHYLE SRVEAFLITM EKAIEDMTEE AFQKHIQALA IRRLDKPKKL
910 920 930 940 950
SAECAKYWGE IISQQYNYDR DNIEVAYLKT LTKDDIIRFY QEMLAVDAPR
960 970 980 990 1000
RHKVSVHVLA REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR
1010
GLPLFPLVKP HINFMAAKL
Length:1,019
Mass (Da):117,772
Last modified:October 1, 2000 - v1
Checksum:i9443A6886110BE86
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278422 mRNA. Translation: CAC01233.1.
UniGeneiMm.28366.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278422 mRNA. Translation: CAC01233.1.
UniGeneiMm.28366.

3D structure databases

ProteinModelPortaliQ9JHR7.
SMRiQ9JHR7. Positions 42-1011.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60044N.

Protein family/group databases

MEROPSiM16.002.

PTM databases

PhosphoSiteiQ9JHR7.

Proteomic databases

MaxQBiQ9JHR7.
PaxDbiQ9JHR7.
PRIDEiQ9JHR7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:96412. Ide.

Phylogenomic databases

eggNOGiCOG1025.
HOVERGENiHBG106799.
InParanoidiQ9JHR7.

Miscellaneous databases

ChiTaRSiIde. mouse.
PROiQ9JHR7.
SOURCEiSearch...

Gene expression databases

CleanExiMM_IDE.
GenevestigatoriQ9JHR7.

Family and domain databases

Gene3Di3.30.830.10. 4 hits.
InterProiIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 4 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Search for PTS1-containing protein in mammals."
    Van Veldhoven P.P.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Functional relevance of a novel SlyX motif in non-conventional secretion of insulin-degrading enzyme."
    Glebov K., Schutze S., Walter J.
    J. Biol. Chem. 286:22711-22715(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, IDENTIFICATION OF SLYX MOTIF, MUTAGENESIS OF 853-GLU--TYR-858.
  3. "Loss of mPer2 increases plasma insulin levels by enhanced glucose-stimulated insulin secretion and impaired insulin clearance in mice."
    Zhao Y., Zhang Y., Zhou M., Wang S., Hua Z., Zhang J.
    FEBS Lett. 586:1306-1311(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  4. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-192 AND LYS-697, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiIDE_MOUSE
AccessioniPrimary (citable) accession number: Q9JHR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: October 1, 2000
Last modified: March 4, 2015
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

ATP-binding induces a conformation change.By similarity

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.