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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

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi108 – 1081Zinc
Active sitei111 – 1111Proton acceptorPROSITE-ProRule annotation
Metal bindingi112 – 1121Zinc
Metal bindingi189 – 1891Zinc
Binding sitei429 – 4291ATP

Regions

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

GO - Molecular functioni

  1. ATPase activity Source: RGD
  2. ATP binding Source: UniProtKB
  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-KW
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 enzymePRO_0000074406Add
BLAST

Amino acid modifications

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

1
1019
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi47 – 515Combined sources
Beta strandi63 – 697Combined sources
Beta strandi74 – 796Combined sources
Beta strandi84 – 9310Combined sources
Helixi96 – 983Combined sources
Beta strandi101 – 1033Combined sources
Helixi106 – 1149Combined sources
Beta strandi118 – 1214Combined sources
Helixi126 – 1327Combined sources
Turni133 – 1353Combined sources
Beta strandi137 – 1426Combined sources
Beta strandi147 – 1548Combined sources
Helixi155 – 1573Combined sources
Helixi158 – 1669Combined sources
Helixi167 – 1693Combined sources
Helixi176 – 19419Combined sources
Helixi197 – 20610Combined sources
Beta strandi211 – 2133Combined sources
Helixi214 – 2163Combined sources
Helixi223 – 2264Combined sources
Helixi228 – 2325Combined sources
Helixi237 – 24812Combined sources
Helixi251 – 2533Combined sources
Beta strandi254 – 2629Combined sources
Helixi264 – 27512Combined sources
Helixi295 – 2973Combined sources
Beta strandi298 – 3058Combined sources
Beta strandi307 – 3093Combined sources
Beta strandi312 – 3209Combined sources
Helixi323 – 3253Combined sources
Turni326 – 3283Combined sources
Helixi330 – 3389Combined sources
Helixi346 – 3527Combined sources
Beta strandi355 – 36713Combined sources
Beta strandi370 – 37910Combined sources
Helixi381 – 3855Combined sources
Helixi387 – 40418Combined sources
Helixi408 – 42316Combined sources
Helixi430 – 44011Combined sources
Turni441 – 4433Combined sources
Helixi446 – 4483Combined sources
Turni449 – 4546Combined sources
Helixi461 – 47010Combined sources
Helixi473 – 4753Combined sources
Beta strandi477 – 4815Combined sources
Helixi483 – 4853Combined sources
Turni494 – 4963Combined sources
Beta strandi499 – 5046Combined sources
Helixi507 – 5148Combined sources
Beta strandi549 – 5535Combined sources
Beta strandi555 – 5639Combined sources
Beta strandi570 – 57910Combined sources
Helixi581 – 5833Combined sources
Beta strandi584 – 5863Combined sources
Helixi587 – 61327Combined sources
Beta strandi616 – 6227Combined sources
Beta strandi624 – 63512Combined sources
Helixi638 – 65013Combined sources
Helixi656 – 67217Combined sources
Helixi673 – 6753Combined sources
Helixi678 – 69013Combined sources
Beta strandi691 – 6933Combined sources
Helixi697 – 7048Combined sources
Helixi709 – 72113Combined sources
Beta strandi722 – 73211Combined sources
Helixi735 – 75319Combined sources
Helixi760 – 7623Combined sources
Beta strandi775 – 7828Combined sources
Beta strandi787 – 79913Combined sources
Helixi802 – 82322Combined sources
Turni824 – 8274Combined sources
Beta strandi833 – 8408Combined sources
Beta strandi843 – 85412Combined sources
Helixi856 – 87520Combined sources
Helixi879 – 89416Combined sources
Helixi900 – 91213Combined sources
Helixi920 – 92910Combined sources
Helixi933 – 94311Combined sources
Beta strandi952 – 9598Combined sources
Beta strandi990 – 9934Combined sources
Helixi995 – 10006Combined sources

3D structure databases

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

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.Curated

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

« 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 .
PIRi S29509.
RefSeqi NP_037291.1. NM_013159.1.
UniGenei Rn.202992.
Rn.45029.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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: November 26, 2014
This is version 122 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