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P35559

- IDE_RAT

UniProt

P35559 - IDE_RAT

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Protein
Insulin-degrading enzyme
Gene
Ide
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

Binds 1 zinc ion per subunit.1 Publication

Enzyme regulationi

Activated by ATP, other nucleotide triphosphates and small peptides. Inhibited by bacitracin By similarity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi108 – 1081Zinc
Active sitei111 – 1111Proton acceptor By similarity
Metal bindingi112 – 1121Zinc
Metal bindingi189 – 1891Zinc
Binding sitei429 – 4291ATP

Regions

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

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. ATPase activity Source: RGD
  3. beta-amyloid binding Source: RGD
  4. beta-endorphin binding Source: RGD
  5. insulin binding Source: RGD
  6. metalloendopeptidase activity Source: UniProtKB
  7. peptidase activity Source: RGD
  8. peptide hormone binding Source: RGD
  9. protein homodimerization activity Source: RGD
  10. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. beta-amyloid metabolic process Source: UniProtKB
  3. bradykinin catabolic process Source: UniProtKB
  4. cellular protein catabolic process Source: RGD
  5. determination of adult lifespan Source: Ensembl
  6. hormone catabolic process Source: RGD
  7. insulin catabolic process Source: Ensembl
  8. negative regulation of proteolysis Source: RGD
  9. peptide catabolic process Source: RGD
  10. positive regulation of protein oligomerization Source: Ensembl
  11. protein heterooligomerization Source: RGD
  12. protein homotetramerization Source: RGD
  13. proteolysis involved in cellular protein catabolic process Source: RGD
  14. 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

SABIO-RKP35559.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 1

Organism-specific databases

RGDi2861. Ide.

Subcellular locationi

Cytoplasm. Cell membrane By similarity. Secreted By similarity

GO - Cellular componenti

  1. cell surface Source: RGD
  2. cytosol Source: RGD
  3. cytosolic proteasome complex Source: RGD
  4. extracellular space Source: RGD
  5. mitochondrion Source: Ensembl
  6. nucleus Source: RGD
  7. peroxisomal matrix Source: RGD
  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
Mutagenesisi429 – 4291R → S: Greatly decreased activation by polyphosphate anions. 1 Publication
Mutagenesisi898 – 8981K → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-899 and A-901. 1 Publication
Mutagenesisi899 – 8991K → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-898 and A-901. 1 Publication
Mutagenesisi901 – 9011S → A: Greatly decreased activation by polyphosphate anions, and deficient in activation by small peptides; when associated with A-898 and A-899. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10191019Insulin-degrading enzyme
PRO_0000074406Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei192 – 1921N6-succinyllysine By similarity
Modified residuei697 – 6971N6-succinyllysine By similarity

Proteomic databases

PaxDbiP35559.
PRIDEiP35559.

PTM databases

PhosphoSiteiP35559.

Expressioni

Gene expression databases

GenevestigatoriP35559.

Interactioni

Subunit structurei

Homodimer. Can form higher oligomers.1 Publication

Protein-protein interaction databases

BioGridi247729. 1 interaction.
STRINGi10116.ENSRNOP00000023342.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi47 – 515
Beta strandi63 – 697
Beta strandi74 – 796
Beta strandi84 – 9310
Helixi96 – 983
Beta strandi101 – 1033
Helixi106 – 1149
Beta strandi118 – 1214
Helixi126 – 1327
Turni133 – 1353
Beta strandi137 – 1426
Beta strandi147 – 1548
Helixi155 – 1573
Helixi158 – 1669
Helixi167 – 1693
Helixi176 – 19419
Helixi197 – 20610
Beta strandi211 – 2133
Helixi214 – 2163
Helixi223 – 2264
Helixi228 – 2325
Helixi237 – 24812
Helixi251 – 2533
Beta strandi254 – 2629
Helixi264 – 27512
Helixi295 – 2973
Beta strandi298 – 3058
Beta strandi307 – 3093
Beta strandi312 – 3209
Helixi323 – 3253
Turni326 – 3283
Helixi330 – 3389
Helixi346 – 3527
Beta strandi355 – 36713
Beta strandi370 – 37910
Helixi381 – 3855
Helixi387 – 40418
Helixi408 – 42316
Helixi430 – 44011
Turni441 – 4433
Helixi446 – 4483
Turni449 – 4546
Helixi461 – 47010
Helixi473 – 4753
Beta strandi477 – 4815
Helixi483 – 4853
Turni494 – 4963
Beta strandi499 – 5046
Helixi507 – 5148
Beta strandi549 – 5535
Beta strandi555 – 5639
Beta strandi570 – 57910
Helixi581 – 5833
Beta strandi584 – 5863
Helixi587 – 61327
Beta strandi616 – 6227
Beta strandi624 – 63512
Helixi638 – 65013
Helixi656 – 67217
Helixi673 – 6753
Helixi678 – 69013
Beta strandi691 – 6933
Helixi697 – 7048
Helixi709 – 72113
Beta strandi722 – 73211
Helixi735 – 75319
Helixi760 – 7623
Beta strandi775 – 7828
Beta strandi787 – 79913
Helixi802 – 82322
Turni824 – 8274
Beta strandi833 – 8408
Beta strandi843 – 85412
Helixi856 – 87520
Helixi879 – 89416
Helixi900 – 91213
Helixi920 – 92910
Helixi933 – 94311
Beta strandi952 – 9598
Beta strandi990 – 9934
Helixi995 – 10006

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3P7LX-ray2.08A42-1019[»]
3P7OX-ray2.14A1-1019[»]
3TUVX-ray2.27A1-1019[»]
ProteinModelPortaliP35559.
SMRiP35559. Positions 43-1016.

Miscellaneous databases

EvolutionaryTraceiP35559.

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 By similarity.

Sequence similaritiesi

Belongs to the peptidase M16 family.

Phylogenomic databases

eggNOGiCOG1025.
GeneTreeiENSGT00530000063327.
HOGENOMiHOG000161331.
HOVERGENiHBG106799.
InParanoidiP35559.
KOiK01408.
OMAiSIFHIIK.
OrthoDBiEOG7HHWRD.
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.
[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.

P35559-1 [UniParc]FASTAAdd to Basket

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MRNGLVWLLH PALPSTLHSI LGARPPPVKR LCGFPKQIYS TMNNPAIQRI     50
EDHIVKSPED KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP 100
PNIPGLSHFC EHMLFLGTKK YPKENEYSQF LSEHAGSSNA FTSGEHTNYY 150
FDVSHEHLEG ALDRFAQFFL CPLFDASCKD REVNAVDSEH EKNVMNDAWR 200
LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE LLKFHSTYYS 250
SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ 300
LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GHYLGHLIGH EGPGSLLSEL 350
KSKGWVNTLV GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK 400
LRAEGPQEWV FQECKDLNAV AFRFKDKERP RGYTSKIAGK LHYYPLNGVL 450
TAEYLLEEFR PDLIDMVLDK LRPENVRVAI VSKSFEGKTD RTEQWYGTQY 500
KQEAIPEDVI QKWQNADLNG KFKLPTKNEF IPTNFEILAL EKDATPYPAL 550
IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 600
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKITEKMA 650
TFEIDKKRFE IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL 700
KEALDDVTLP RLKAFIPQLL SRLHIEALLH GNITKQAALG VMQMVEDTLI 750
EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ RRNEVHNNCG IEIYYQTDMQ 800
STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA NGIQGLRFII 850
QSEKPPHYLE SRVEAFLITM EKAIEDMTEE AFQKHIQALA IRRLDKPKKL 900
SAECAKYWGE IISQQYNYDR DNIEVAYLKT LSKDDIIKFY KEMLAVDAPR 950
RHKVSVHVLA REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR 1000
GLPLFPLVKP HINFMAAKL 1019
Length:1,019
Mass (Da):117,710
Last modified:June 1, 1994 - v1
Checksum:i9DB297A7F1877CEC
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
X67269 mRNA. Translation: CAA47689.1 .
S53721 mRNA. Translation: AAB25205.1 .
PIRi S29509.
RefSeqi NP_037291.1. NM_013159.1.
UniGenei Rn.202992.
Rn.45029.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3P7L X-ray 2.08 A 42-1019 [» ]
3P7O X-ray 2.14 A 1-1019 [» ]
3TUV X-ray 2.27 A 1-1019 [» ]
ProteinModelPortali P35559.
SMRi P35559. Positions 43-1016.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247729. 1 interaction.
STRINGi 10116.ENSRNOP00000023342.

Protein family/group databases

MEROPSi M16.002.

PTM databases

PhosphoSitei P35559.

Proteomic databases

PaxDbi P35559.
PRIDEi P35559.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000023342 ; ENSRNOP00000023342 ; ENSRNOG00000016833 .
GeneIDi 25700.
KEGGi rno:25700.
UCSCi RGD:2861. rat.

Organism-specific databases

CTDi 3416.
RGDi 2861. Ide.

Phylogenomic databases

eggNOGi COG1025.
GeneTreei ENSGT00530000063327.
HOGENOMi HOG000161331.
HOVERGENi HBG106799.
InParanoidi P35559.
KOi K01408.
OMAi SIFHIIK.
OrthoDBi EOG7HHWRD.
PhylomeDBi P35559.
TreeFami TF106275.

Enzyme and pathway databases

SABIO-RK P35559.

Miscellaneous databases

EvolutionaryTracei P35559.
NextBioi 607727.
PROi P35559.

Gene expression databases

Genevestigatori P35559.

Family and domain databases

Gene3Di 3.30.830.10. 4 hits.
InterProi IPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view ]
Pfami PF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view ]
SUPFAMi SSF63411. SSF63411. 4 hits.
PROSITEi PS00143. INSULINASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "The rat insulin-degrading enzyme. Molecular cloning and characterization of tissue-specific transcripts."
    Baumeister H., Mueller D., Rehbein M., Richter D.
    FEBS Lett. 317:250-254(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Brain.
  2. "Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues."
    Kuo W.L., Montag A.G., Rosner M.R.
    Endocrinology 132:604-611(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 898-995.
    Strain: Sprague-Dawley.
  3. "Atrial natriuretic peptide (ANP) is a high-affinity substrate for rat insulin-degrading enzyme."
    Mueller D., Baumeister H., Buck F., Richter D.
    Eur. J. Biochem. 202:285-292(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE, ACTIVITY ON ANP.
  4. "Rat insulin-degrading enzyme: cleavage pattern of the natriuretic peptide hormones ANP, BNP, and CNP revealed by HPLC and mass spectrometry."
    Mueller D., Schulze C., Baumeister H., Buck F., Richter D.
    Biochemistry 31:11138-11143(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACTIVITY ON ANP; BNP AND CNP.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 42-1019 OF WILD TYPE AND MUTANT PHE-111, SUBUNIT, COFACTOR, ZINC-BINDING SITES, ENZYME REGULATION, ALLOSTERIC REGULATION.
  6. Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS), ATP-BINDING SITE, MUTAGENESIS OF ARG-429; LYS-898; LYS-899 AND SER-901.

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: September 3, 2014
This is version 119 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

External Data

Dasty 3

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