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P35559

- IDE_RAT

UniProt

P35559 - IDE_RAT

Protein

Insulin-degrading enzyme

Gene

Ide

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    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.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

    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

    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 – 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.
    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

    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: October 1, 2014
    This is version 120 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