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Protein

Insulin-degrading enzyme

Gene

Ide

Organism
Rattus norvegicus (Rat)
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.

Catalytic activityi

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

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi108Zinc1
Active sitei111Proton acceptorPROSITE-ProRule annotation1
Metal bindingi112Zinc1
Metal bindingi189Zinc1
Binding sitei429ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi895 – 901ATP7

GO - Molecular functioni

  • ATPase activity Source: RGD
  • ATP binding Source: UniProtKB
  • beta-amyloid binding Source: RGD
  • beta-endorphin binding Source: RGD
  • glycoprotein binding Source: Ensembl
  • insulin binding Source: RGD
  • metalloendopeptidase activity Source: UniProtKB
  • peptidase activity Source: RGD
  • peptide hormone binding Source: RGD
  • protein homodimerization activity Source: RGD
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • beta-amyloid metabolic process Source: UniProtKB
  • bradykinin catabolic process Source: UniProtKB
  • cellular protein catabolic process Source: RGD
  • determination of adult lifespan Source: Ensembl
  • hormone catabolic process Source: RGD
  • insulin catabolic process Source: Ensembl
  • negative regulation of proteolysis Source: RGD
  • peptide catabolic process Source: RGD
  • positive regulation of protein oligomerization Source: Ensembl
  • protein heterooligomerization Source: RGD
  • protein homotetramerization Source: RGD
  • protein processing Source: GO_Central
  • proteolysis involved in cellular protein catabolic process Source: RGD
  • ubiquitin homeostasis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

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

Enzyme and pathway databases

BRENDAi3.4.24.56. 5301.
SABIO-RKP35559.

Protein family/group databases

MEROPSiM16.982.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2861. Ide.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: RGD
  • cytosol Source: RGD
  • cytosolic proteasome complex Source: RGD
  • extracellular space Source: RGD
  • mitochondrion Source: GO_Central
  • nucleoplasm Source: Ensembl
  • nucleus Source: RGD
  • peroxisomal matrix Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi429R → S: Greatly decreased activation by polyphosphate anions. 1 Publication1
Mutagenesisi898K → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-899 and A-901. 1 Publication1
Mutagenesisi899K → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-898 and A-901. 1 Publication1
Mutagenesisi901S → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-898 and A-899. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000744061 – 1019Insulin-degrading enzymeAdd BLAST1019

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei192N6-succinyllysineBy similarity1
Modified residuei697N6-succinyllysineBy similarity1

Proteomic databases

PaxDbiP35559.
PRIDEiP35559.

PTM databases

iPTMnetiP35559.
PhosphoSitePlusiP35559.

Expressioni

Gene expression databases

BgeeiENSRNOG00000016833.
ExpressionAtlasiP35559. baseline and differential.
GenevisibleiP35559. RN.

Interactioni

Subunit structurei

Homodimer. Can form higher oligomers.1 Publication

GO - Molecular functioni

  • insulin binding Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

BioGridi247729. 1 interactor.
STRINGi10116.ENSRNOP00000023342.

Structurei

Secondary structure

11019
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi47 – 51Combined sources5
Beta strandi63 – 69Combined sources7
Beta strandi74 – 79Combined sources6
Beta strandi84 – 93Combined sources10
Helixi96 – 98Combined sources3
Beta strandi101 – 103Combined sources3
Helixi106 – 114Combined sources9
Beta strandi118 – 121Combined sources4
Helixi126 – 132Combined sources7
Turni133 – 135Combined sources3
Beta strandi137 – 142Combined sources6
Beta strandi147 – 154Combined sources8
Helixi155 – 157Combined sources3
Helixi158 – 166Combined sources9
Helixi167 – 169Combined sources3
Helixi176 – 194Combined sources19
Helixi197 – 206Combined sources10
Beta strandi211 – 213Combined sources3
Helixi214 – 216Combined sources3
Helixi223 – 226Combined sources4
Helixi228 – 232Combined sources5
Helixi237 – 248Combined sources12
Helixi251 – 253Combined sources3
Beta strandi254 – 262Combined sources9
Helixi264 – 275Combined sources12
Helixi295 – 297Combined sources3
Beta strandi298 – 305Combined sources8
Beta strandi307 – 309Combined sources3
Beta strandi312 – 320Combined sources9
Helixi323 – 325Combined sources3
Turni326 – 328Combined sources3
Helixi330 – 338Combined sources9
Helixi346 – 352Combined sources7
Beta strandi355 – 367Combined sources13
Beta strandi370 – 379Combined sources10
Helixi381 – 385Combined sources5
Helixi387 – 404Combined sources18
Helixi408 – 423Combined sources16
Helixi430 – 440Combined sources11
Turni441 – 443Combined sources3
Helixi446 – 448Combined sources3
Turni449 – 454Combined sources6
Helixi461 – 470Combined sources10
Helixi473 – 475Combined sources3
Beta strandi477 – 481Combined sources5
Helixi483 – 485Combined sources3
Turni494 – 496Combined sources3
Beta strandi499 – 504Combined sources6
Helixi507 – 514Combined sources8
Beta strandi549 – 553Combined sources5
Beta strandi555 – 563Combined sources9
Beta strandi570 – 579Combined sources10
Helixi581 – 583Combined sources3
Beta strandi584 – 586Combined sources3
Helixi587 – 613Combined sources27
Beta strandi616 – 622Combined sources7
Beta strandi624 – 635Combined sources12
Helixi638 – 650Combined sources13
Helixi656 – 672Combined sources17
Helixi673 – 675Combined sources3
Helixi678 – 690Combined sources13
Beta strandi691 – 693Combined sources3
Helixi697 – 704Combined sources8
Helixi709 – 721Combined sources13
Beta strandi722 – 732Combined sources11
Helixi735 – 753Combined sources19
Helixi760 – 762Combined sources3
Beta strandi775 – 782Combined sources8
Beta strandi787 – 799Combined sources13
Helixi802 – 823Combined sources22
Turni824 – 827Combined sources4
Beta strandi833 – 840Combined sources8
Beta strandi843 – 854Combined sources12
Helixi856 – 875Combined sources20
Helixi879 – 894Combined sources16
Helixi900 – 912Combined sources13
Helixi920 – 929Combined sources10
Helixi933 – 943Combined sources11
Beta strandi952 – 959Combined sources8
Beta strandi990 – 993Combined sources4
Helixi995 – 1000Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P7LX-ray2.08A42-1019[»]
3P7OX-ray2.14A1-1019[»]
3TUVX-ray2.27A1-1019[»]
ProteinModelPortaliP35559.
SMRiP35559.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35559.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi853 – 858SlyX motif6

Domaini

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

Sequence similaritiesi

Belongs to the peptidase M16 family.Curated

Phylogenomic databases

eggNOGiKOG0959. Eukaryota.
COG1025. LUCA.
GeneTreeiENSGT00530000063327.
HOGENOMiHOG000161331.
HOVERGENiHBG106799.
InParanoidiP35559.
KOiK01408.
OMAiLINQVME.
OrthoDBiEOG091G0255.
PhylomeDBiP35559.
TreeFamiTF106275.

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.
IPR032632. Peptidase_M16_M.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
PF16187. Peptidase_M16_M. 1 hit.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 4 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35559-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRNGLVWLLH PALPSTLHSI LGARPPPVKR LCGFPKQIYS TMNNPAIQRI
60 70 80 90 100
EDHIVKSPED KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP
110 120 130 140 150
PNIPGLSHFC EHMLFLGTKK YPKENEYSQF LSEHAGSSNA FTSGEHTNYY
160 170 180 190 200
FDVSHEHLEG ALDRFAQFFL CPLFDASCKD REVNAVDSEH EKNVMNDAWR
210 220 230 240 250
LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE LLKFHSTYYS
260 270 280 290 300
SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ
310 320 330 340 350
LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GHYLGHLIGH 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 IPTNFEILAL EKDATPYPAL
560 570 580 590 600
IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL
610 620 630 640 650
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI 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 RRNEVHNNCG 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 LSKDDIIKFY KEMLAVDAPR
960 970 980 990 1000
RHKVSVHVLA REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR
1010
GLPLFPLVKP HINFMAAKL
Length:1,019
Mass (Da):117,710
Last modified:June 1, 1994 - v1
Checksum:i9DB297A7F1877CEC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67269 mRNA. Translation: CAA47689.1.
S53721 mRNA. Translation: AAB25205.1.
PIRiS29509.
RefSeqiNP_037291.1. NM_013159.1.
UniGeneiRn.202992.
Rn.45029.

Genome annotation databases

EnsembliENSRNOT00000023342; ENSRNOP00000023342; ENSRNOG00000016833.
GeneIDi25700.
KEGGirno:25700.
UCSCiRGD:2861. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67269 mRNA. Translation: CAA47689.1.
S53721 mRNA. Translation: AAB25205.1.
PIRiS29509.
RefSeqiNP_037291.1. NM_013159.1.
UniGeneiRn.202992.
Rn.45029.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P7LX-ray2.08A42-1019[»]
3P7OX-ray2.14A1-1019[»]
3TUVX-ray2.27A1-1019[»]
ProteinModelPortaliP35559.
SMRiP35559.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247729. 1 interactor.
STRINGi10116.ENSRNOP00000023342.

Protein family/group databases

MEROPSiM16.982.

PTM databases

iPTMnetiP35559.
PhosphoSitePlusiP35559.

Proteomic databases

PaxDbiP35559.
PRIDEiP35559.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000023342; ENSRNOP00000023342; ENSRNOG00000016833.
GeneIDi25700.
KEGGirno:25700.
UCSCiRGD:2861. rat.

Organism-specific databases

CTDi3416.
RGDi2861. Ide.

Phylogenomic databases

eggNOGiKOG0959. Eukaryota.
COG1025. LUCA.
GeneTreeiENSGT00530000063327.
HOGENOMiHOG000161331.
HOVERGENiHBG106799.
InParanoidiP35559.
KOiK01408.
OMAiLINQVME.
OrthoDBiEOG091G0255.
PhylomeDBiP35559.
TreeFamiTF106275.

Enzyme and pathway databases

BRENDAi3.4.24.56. 5301.
SABIO-RKP35559.

Miscellaneous databases

EvolutionaryTraceiP35559.
PROiP35559.

Gene expression databases

BgeeiENSRNOG00000016833.
ExpressionAtlasiP35559. baseline and differential.
GenevisibleiP35559. RN.

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.
IPR032632. Peptidase_M16_M.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
PF16187. Peptidase_M16_M. 1 hit.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 4 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIDE_RAT
AccessioniPrimary (citable) accession number: P35559
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 139 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

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.