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Q9JHR7 (IDE_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-degrading enzyme

EC=3.4.24.56
Alternative name(s):
Insulin protease
Short name=Insulinase
Insulysin
Gene names
Name:Ide
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1019 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity.

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

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

Subunit structure

Homodimer. Can form higher oligomers By similarity.

Subcellular location

Cytoplasm. Cell membrane. Secreted Ref.2.

Induction

Expression oscillates diurnally. Ref.3

Domain

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

Miscellaneous

ATP-binding induces a conformation change By similarity.

Sequence similarities

Belongs to the peptidase M16 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10191019Insulin-degrading enzyme
PRO_0000074405

Regions

Nucleotide binding895 – 9017ATP By similarity
Motif853 – 8586SlyX motif

Sites

Active site1111Proton acceptor By similarity
Metal binding1081Zinc By similarity
Metal binding1121Zinc By similarity
Metal binding1891Zinc By similarity
Binding site4291ATP By similarity

Amino acid modifications

Modified residue1921N6-succinyllysine Ref.4
Modified residue6971N6-succinyllysine Ref.4

Experimental info

Mutagenesis853 – 8586Missing: Marked decrease in secretion. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9JHR7 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 9443A6886110BE86

FASTA1,019117,772
        10         20         30         40         50         60 
MRNGLVWLLH PALPGTLRSI LGARPPPAKR LCGFPKQTYS TMSNPAIQRI EDQIVKSPED 

        70         80         90        100        110        120 
KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP PNIPGLSHFC EHMLFLGTKK 

       130        140        150        160        170        180 
YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLLDASCKD 

       190        200        210        220        230        240 
REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE 

       250        260        270        280        290        300 
LLKFHSTYYS SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLRQ 

       310        320        330        340        350        360 
LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GYYLGHLIGH EGPGSLLSEL KSKGWVNTLV 

       370        380        390        400        410        420 
GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV 

       430        440        450        460        470        480 
AFRFKDKERP RGYTSKIAGK LHYYPLNGVL TAEYLLEEFR PDLIDMVLDK LRPENVRVAI 

       490        500        510        520        530        540 
VSKSFEGKTD RTEQWYGTQY KQEAIPEDVI QKWQNADLNG KFKLPTKNEF IPTNFEILSL 

       550        560        570        580        590        600 
EKDATPYPAL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 

       610        620        630        640        650        660 
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKRYNDKQPI LLKKITEKMA TFEIDKKRFE 

       670        680        690        700        710        720 
IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL 

       730        740        750        760        770        780 
SRLHIEALLH GNITKQAALG VMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ 

       790        800        810        820        830        840 
QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA 

       850        860        870        880        890        900 
NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKAIEDMTEE AFQKHIQALA IRRLDKPKKL 

       910        920        930        940        950        960 
SAECAKYWGE IISQQYNYDR DNIEVAYLKT LTKDDIIRFY QEMLAVDAPR RHKVSVHVLA 

       970        980        990       1000       1010 
REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR GLPLFPLVKP HINFMAAKL 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ278422 mRNA. Translation: CAC01233.1.
UniGeneMm.28366.

3D structure databases

ProteinModelPortalQ9JHR7.
SMRQ9JHR7. Positions 42-1011.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-60044N.

Protein family/group databases

MEROPSM16.002.

PTM databases

PhosphoSiteQ9JHR7.

Proteomic databases

MaxQBQ9JHR7.
PaxDbQ9JHR7.
PRIDEQ9JHR7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:96412. Ide.

Phylogenomic databases

eggNOGCOG1025.
HOVERGENHBG106799.
InParanoidQ9JHR7.

Gene expression databases

CleanExMM_IDE.
GenevestigatorQ9JHR7.

Family and domain databases

Gene3D3.30.830.10. 4 hits.
InterProIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
SUPFAMSSF63411. SSF63411. 4 hits.
PROSITEPS00143. INSULINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIDE. mouse.
PROQ9JHR7.
SOURCESearch...

Entry information

Entry nameIDE_MOUSE
AccessionPrimary (citable) accession number: Q9JHR7
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot