Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P14735

- IDE_HUMAN

UniProt

P14735 - IDE_HUMAN

Protein

Insulin-degrading enzyme

Gene

IDE

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 4 (25 Nov 2008)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.3 Publications

    Catalytic activityi

    Degradation of insulin, glucagon and other polypeptides. No action on proteins.1 Publication

    Cofactori

    Binds 1 zinc ion per subunit.1 Publication

    Enzyme regulationi

    Activated by small peptides By similarity. Activated by ATP and GTP, and to a lesser extent by CTP, TTP and PPPi. Inhibited by bacitracin. Inhibited by S-nitrosylation and oxidation agents.By similarity2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi108 – 1081ZincPROSITE-ProRule annotation
    Active sitei111 – 1111Proton acceptorPROSITE-ProRule annotation
    Metal bindingi112 – 1121ZincPROSITE-ProRule annotation
    Metal bindingi189 – 1891ZincPROSITE-ProRule annotation
    Binding sitei429 – 4291ATPBy similarity

    Regions

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

    GO - Molecular functioni

    1. ATPase activity Source: Ensembl
    2. ATP binding Source: UniProtKB
    3. beta-amyloid binding Source: Ensembl
    4. beta-endorphin binding Source: Ensembl
    5. glycoprotein binding Source: UniProtKB
    6. insulin binding Source: UniProtKB
    7. metalloendopeptidase activity Source: UniProtKB
    8. peptide binding Source: UniProtKB
    9. protein binding Source: UniProtKB
    10. protein homodimerization activity Source: UniProtKB
    11. receptor binding Source: UniProtKB
    12. ubiquitin binding Source: UniProtKB
    13. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. beta-amyloid metabolic process Source: UniProtKB
    2. bradykinin catabolic process Source: UniProtKB
    3. determination of adult lifespan Source: UniProtKB
    4. hormone catabolic process Source: Ensembl
    5. insulin catabolic process Source: UniProtKB
    6. insulin metabolic process Source: UniProtKB
    7. insulin receptor signaling pathway Source: UniProtKB
    8. negative regulation of proteolysis Source: Ensembl
    9. positive regulation of protein oligomerization Source: UniProtKB
    10. protein heterooligomerization Source: Ensembl
    11. protein homooligomerization Source: UniProtKB
    12. protein homotetramerization Source: Ensembl
    13. proteolysis Source: UniProtKB
    14. proteolysis involved in cellular protein catabolic process Source: UniProtKB
    15. ubiquitin homeostasis Source: UniProtKB
    16. viral process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Host-virus interaction

    Keywords - Ligandi

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

    Enzyme and pathway databases

    SignaLinkiP14735.

    Protein family/group databases

    MEROPSiM16.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin-degrading enzyme (EC:3.4.24.56)
    Alternative name(s):
    Abeta-degrading protease
    Insulin protease
    Short name:
    Insulinase
    Insulysin
    Gene namesi
    Name:IDE
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:5381. IDE.

    Subcellular locationi

    Cytoplasm. Cell membrane. Secreted By similarity
    Note: Present at the cell surface of neuron cells. The membrane-associated isoform is approximately 5 kDa larger than the known cytosolic isoform.

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: UniProtKB
    4. cytosolic proteasome complex Source: Ensembl
    5. extracellular space Source: UniProtKB
    6. mitochondrion Source: UniProtKB
    7. nucleus Source: UniProtKB
    8. peroxisomal matrix Source: Ensembl
    9. peroxisome Source: UniProtKB
    10. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi111 – 1111E → Q: Loss of catalytic activity. 1 Publication
    Mutagenesisi132 – 1321S → C: Increases catalytic rate towards INS and amyloid; when associated with C-817. 1 Publication
    Mutagenesisi184 – 1841N → C: Increases catalytic rate towards INS and amyloid; when associated with C-828. 1 Publication
    Mutagenesisi426 – 4261D → C: Increases catalytic rate towards INS and amyloid; when associated with C-899. 2 Publications
    Mutagenesisi817 – 8171E → C: Increases catalytic rate towards INS and amyloid; when associated with C-132. 1 Publication
    Mutagenesisi828 – 8281Q → C: Increases catalytic rate towards INS and amyloid; when associated with C-184. 1 Publication
    Mutagenesisi831 – 8311Y → F: No effect on catalytic activity.
    Mutagenesisi899 – 8991K → C: Increases catalytic rate towards INS and amyloid; when associated with C-426. 2 Publications

    Organism-specific databases

    PharmGKBiPA29629.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10191019Insulin-degrading enzymePRO_0000074404Add
    BLAST

    Amino acid modifications

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

    Post-translational modificationi

    The N-terminus is blocked.

    Proteomic databases

    MaxQBiP14735.
    PaxDbiP14735.
    PRIDEiP14735.

    PTM databases

    PhosphoSiteiP14735.

    Expressioni

    Gene expression databases

    ArrayExpressiP14735.
    BgeeiP14735.
    CleanExiHS_IDE.
    GenevestigatoriP14735.

    Organism-specific databases

    HPAiCAB012303.

    Interactioni

    Subunit structurei

    Homodimer. Can form higher oligomers. Interacts (via N-terminus) with varicella-zoster virus (VZV) envelope glycoprotein E (via N-terminus); the membrane-associated isoform may function as an entry receptor for this virus.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCL3P101473EBI-2556886,EBI-8459634

    Protein-protein interaction databases

    BioGridi109642. 27 interactions.
    DIPiDIP-55771N.
    IntActiP14735. 5 interactions.
    MINTiMINT-2801173.
    STRINGi9606.ENSP00000265986.

    Structurei

    Secondary structure

    1
    1019
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi47 – 504
    Beta strandi63 – 697
    Beta strandi74 – 796
    Beta strandi84 – 9310
    Helixi96 – 983
    Beta strandi101 – 1033
    Helixi106 – 1138
    Helixi114 – 1163
    Beta strandi118 – 1214
    Helixi126 – 1327
    Turni133 – 1353
    Beta strandi137 – 1426
    Beta strandi147 – 1548
    Helixi155 – 1573
    Helixi158 – 1669
    Helixi167 – 1693
    Helixi176 – 19419
    Helixi197 – 20711
    Helixi214 – 2163
    Helixi223 – 2264
    Helixi228 – 2325
    Helixi237 – 24812
    Helixi251 – 2533
    Beta strandi254 – 2629
    Helixi264 – 27512
    Helixi295 – 2973
    Beta strandi298 – 3047
    Beta strandi307 – 3093
    Beta strandi312 – 3198
    Helixi323 – 3253
    Turni326 – 3283
    Helixi330 – 3389
    Helixi346 – 3527
    Beta strandi359 – 3679
    Beta strandi370 – 3789
    Helixi381 – 3855
    Helixi387 – 40418
    Helixi408 – 42316
    Helixi430 – 44011
    Turni441 – 4433
    Helixi446 – 4483
    Turni449 – 4546
    Helixi461 – 4688
    Helixi473 – 4753
    Beta strandi477 – 4815
    Helixi483 – 4853
    Turni486 – 4883
    Turni494 – 4963
    Beta strandi499 – 5046
    Helixi507 – 5148
    Beta strandi549 – 5535
    Beta strandi555 – 5639
    Beta strandi565 – 5673
    Beta strandi570 – 57910
    Helixi581 – 5833
    Beta strandi584 – 5863
    Helixi587 – 61327
    Beta strandi616 – 6238
    Beta strandi626 – 63510
    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 strandi831 – 84010
    Beta strandi843 – 85412
    Helixi856 – 87621
    Helixi879 – 89416
    Helixi900 – 91213
    Helixi920 – 9289
    Helixi933 – 94311
    Beta strandi952 – 9598
    Beta strandi990 – 9923
    Helixi995 – 10006

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2G47X-ray2.10A/B42-1019[»]
    2G48X-ray2.60A/B42-1019[»]
    2G49X-ray2.50A/B42-1019[»]
    2G54X-ray2.25A/B42-1019[»]
    2G56X-ray2.20A/B42-1019[»]
    2JBUX-ray3.00A/B42-1019[»]
    2JG4X-ray2.80A/B43-1019[»]
    2WBYX-ray2.60A/B42-1019[»]
    2WC0X-ray2.80A/B42-1019[»]
    2WK3X-ray2.59A/B1-1019[»]
    2YPUX-ray2.80A/B42-1019[»]
    3CWWX-ray1.96A/B42-1019[»]
    3E4AX-ray2.60A/B1-1019[»]
    3E4ZX-ray2.28A/B42-1019[»]
    3E50X-ray2.30A/B42-1019[»]
    3H44X-ray3.00A/B42-1019[»]
    3HGZX-ray2.91A/B43-1011[»]
    3N56X-ray3.10A/B42-1019[»]
    3N57X-ray3.03A/B42-1019[»]
    3OFIX-ray2.35A/B42-1019[»]
    3QZ2X-ray3.20A/B42-1019[»]
    4DTTX-ray3.22A/B42-1019[»]
    4DWKX-ray3.00A/B42-1019[»]
    4GS8X-ray2.99A/B42-1019[»]
    4GSCX-ray2.81A/B42-1019[»]
    4GSFX-ray2.70A/B42-1019[»]
    4IFHX-ray3.29A/B42-1019[»]
    4IOFX-ray3.35A/B42-1019[»]
    4LTEX-ray2.70A/B42-1019[»]
    ProteinModelPortaliP14735.
    SMRiP14735. Positions 43-1016.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14735.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni336 – 3427Substrate binding exosite
    Regioni359 – 3635Substrate binding

    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.
    HOGENOMiHOG000161331.
    HOVERGENiHBG106799.
    InParanoidiP14735.
    KOiK01408.
    OMAiSIFHIIK.
    OrthoDBiEOG7HHWRD.
    PhylomeDBiP14735.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P14735-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRYRLAWLLH PALPSTFRSV LGARLPPPER LCGFQKKTYS KMNNPAIKRI     50
    GNHITKSPED KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP 100
    PNIAGLSHFC EHMLFLGTKK YPKENEYSQF LSEHAGSSNA FTSGEHTNYY 150
    FDVSHEHLEG ALDRFAQFFL CPLFDESCKD REVNAVDSEH EKNVMNDAWR 200
    LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVRQE LLKFHSAYYS 250
    SNLMAVCVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ 300
    LYKIVPIKDI RNLYVTFPIP DLQKYYKSNP GHYLGHLIGH EGPGSLLSEL 350
    KSKGWVNTLV GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK 400
    LRAEGPQEWV FQECKDLNAV AFRFKDKERP RGYTSKIAGI LHYYPLEEVL 450
    TAEYLLEEFR PDLIEMVLDK LRPENVRVAI VSKSFEGKTD RTEEWYGTQY 500
    KQEAIPDEVI KKWQNADLNG KFKLPTKNEF IPTNFEILPL EKEATPYPAL 550
    IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 600
    KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKIIEKMA 650
    TFEIDEKRFE IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL 700
    KEALDDVTLP RLKAFIPQLL SRLHIEALLH GNITKQAALG IMQMVEDTLI 750
    EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ QRNEVHNNCG IEIYYQTDMQ 800
    STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA NGIQGLRFII 850
    QSEKPPHYLE SRVEAFLITM EKSIEDMTEE AFQKHIQALA IRRLDKPKKL 900
    SAECAKYWGE IISQQYNFDR DNTEVAYLKT LTKEDIIKFY KEMLAVDAPR 950
    RHKVSVHVLA REMDSCPVVG EFPCQNDINL SQAPALPQPE VIQNMTEFKR 1000
    GLPLFPLVKP HINFMAAKL 1019
    Length:1,019
    Mass (Da):117,968
    Last modified:November 25, 2008 - v4
    Checksum:i8A28AEF75EDA0EDA
    GO
    Isoform 2 (identifier: P14735-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-555: Missing.

    Show »
    Length:464
    Mass (Da):54,240
    Checksum:iD51C435A02BA4932
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti78 – 781I → M in AAA52712. (PubMed:2293021)Curated
    Sequence conflicti472 – 4721R → G in BAG35668. (PubMed:14702039)Curated
    Sequence conflicti555 – 5551A → V in AAA52712. (PubMed:2293021)Curated
    Sequence conflicti567 – 5693FFL → KKK in AAA52712. (PubMed:2293021)Curated
    Sequence conflicti586 – 5861D → G in BAG35668. (PubMed:14702039)Curated
    Sequence conflicti845 – 8451G → S in AAA52712. (PubMed:2293021)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti612 – 6121E → K.
    Corresponds to variant rs2229708 [ dbSNP | Ensembl ].
    VAR_051571

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 555555Missing in isoform 2. 1 PublicationVSP_044303Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21188 mRNA. Translation: AAA52712.1.
    AK312810 mRNA. Translation: BAG35668.1.
    AK316407 mRNA. Translation: BAH14778.1.
    AL356128 Genomic DNA. Translation: CAI13670.1.
    CH471066 Genomic DNA. Translation: EAW50090.1.
    CH471066 Genomic DNA. Translation: EAW50091.1.
    BC096336 mRNA. Translation: AAH96336.1.
    BC096337 mRNA. Translation: AAH96337.1.
    BC096339 mRNA. Translation: AAH96339.1.
    CCDSiCCDS53554.1. [P14735-2]
    CCDS7421.1. [P14735-1]
    PIRiA40119. SNHUIN.
    RefSeqiNP_001159418.1. NM_001165946.1. [P14735-2]
    NP_004960.2. NM_004969.3. [P14735-1]
    UniGeneiHs.500546.

    Genome annotation databases

    EnsembliENST00000265986; ENSP00000265986; ENSG00000119912. [P14735-1]
    ENST00000371581; ENSP00000360637; ENSG00000119912. [P14735-2]
    GeneIDi3416.
    KEGGihsa:3416.
    UCSCiuc001kia.3. human. [P14735-1]
    uc010qnp.2. human. [P14735-2]

    Polymorphism databases

    DMDMi215274252.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21188 mRNA. Translation: AAA52712.1 .
    AK312810 mRNA. Translation: BAG35668.1 .
    AK316407 mRNA. Translation: BAH14778.1 .
    AL356128 Genomic DNA. Translation: CAI13670.1 .
    CH471066 Genomic DNA. Translation: EAW50090.1 .
    CH471066 Genomic DNA. Translation: EAW50091.1 .
    BC096336 mRNA. Translation: AAH96336.1 .
    BC096337 mRNA. Translation: AAH96337.1 .
    BC096339 mRNA. Translation: AAH96339.1 .
    CCDSi CCDS53554.1. [P14735-2 ]
    CCDS7421.1. [P14735-1 ]
    PIRi A40119. SNHUIN.
    RefSeqi NP_001159418.1. NM_001165946.1. [P14735-2 ]
    NP_004960.2. NM_004969.3. [P14735-1 ]
    UniGenei Hs.500546.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2G47 X-ray 2.10 A/B 42-1019 [» ]
    2G48 X-ray 2.60 A/B 42-1019 [» ]
    2G49 X-ray 2.50 A/B 42-1019 [» ]
    2G54 X-ray 2.25 A/B 42-1019 [» ]
    2G56 X-ray 2.20 A/B 42-1019 [» ]
    2JBU X-ray 3.00 A/B 42-1019 [» ]
    2JG4 X-ray 2.80 A/B 43-1019 [» ]
    2WBY X-ray 2.60 A/B 42-1019 [» ]
    2WC0 X-ray 2.80 A/B 42-1019 [» ]
    2WK3 X-ray 2.59 A/B 1-1019 [» ]
    2YPU X-ray 2.80 A/B 42-1019 [» ]
    3CWW X-ray 1.96 A/B 42-1019 [» ]
    3E4A X-ray 2.60 A/B 1-1019 [» ]
    3E4Z X-ray 2.28 A/B 42-1019 [» ]
    3E50 X-ray 2.30 A/B 42-1019 [» ]
    3H44 X-ray 3.00 A/B 42-1019 [» ]
    3HGZ X-ray 2.91 A/B 43-1011 [» ]
    3N56 X-ray 3.10 A/B 42-1019 [» ]
    3N57 X-ray 3.03 A/B 42-1019 [» ]
    3OFI X-ray 2.35 A/B 42-1019 [» ]
    3QZ2 X-ray 3.20 A/B 42-1019 [» ]
    4DTT X-ray 3.22 A/B 42-1019 [» ]
    4DWK X-ray 3.00 A/B 42-1019 [» ]
    4GS8 X-ray 2.99 A/B 42-1019 [» ]
    4GSC X-ray 2.81 A/B 42-1019 [» ]
    4GSF X-ray 2.70 A/B 42-1019 [» ]
    4IFH X-ray 3.29 A/B 42-1019 [» ]
    4IOF X-ray 3.35 A/B 42-1019 [» ]
    4LTE X-ray 2.70 A/B 42-1019 [» ]
    ProteinModelPortali P14735.
    SMRi P14735. Positions 43-1016.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109642. 27 interactions.
    DIPi DIP-55771N.
    IntActi P14735. 5 interactions.
    MINTi MINT-2801173.
    STRINGi 9606.ENSP00000265986.

    Chemistry

    BindingDBi P14735.
    ChEMBLi CHEMBL1293287.
    DrugBanki DB00626. Bacitracin.
    DB00047. Insulin Glargine recombinant.
    DB00046. Insulin Lyspro recombinant.
    DB00030. Insulin recombinant.
    DB00071. Insulin, porcine.

    Protein family/group databases

    MEROPSi M16.002.

    PTM databases

    PhosphoSitei P14735.

    Polymorphism databases

    DMDMi 215274252.

    Proteomic databases

    MaxQBi P14735.
    PaxDbi P14735.
    PRIDEi P14735.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000265986 ; ENSP00000265986 ; ENSG00000119912 . [P14735-1 ]
    ENST00000371581 ; ENSP00000360637 ; ENSG00000119912 . [P14735-2 ]
    GeneIDi 3416.
    KEGGi hsa:3416.
    UCSCi uc001kia.3. human. [P14735-1 ]
    uc010qnp.2. human. [P14735-2 ]

    Organism-specific databases

    CTDi 3416.
    GeneCardsi GC10M094211.
    H-InvDB HIX0009042.
    HGNCi HGNC:5381. IDE.
    HPAi CAB012303.
    MIMi 146680. gene.
    neXtProti NX_P14735.
    PharmGKBi PA29629.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1025.
    HOGENOMi HOG000161331.
    HOVERGENi HBG106799.
    InParanoidi P14735.
    KOi K01408.
    OMAi SIFHIIK.
    OrthoDBi EOG7HHWRD.
    PhylomeDBi P14735.
    TreeFami TF106275.

    Enzyme and pathway databases

    SignaLinki P14735.

    Miscellaneous databases

    EvolutionaryTracei P14735.
    GeneWikii Insulin-degrading_enzyme.
    GenomeRNAii 3416.
    NextBioi 13466.
    PROi P14735.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P14735.
    Bgeei P14735.
    CleanExi HS_IDE.
    Genevestigatori P14735.

    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. "Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III."
      Affholter J.A., Fried V.A., Roth R.A.
      Science 242:1415-1418(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
    2. "Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes."
      Affholter J.A., Hsieh C.L., Francke U., Roth R.A.
      Mol. Endocrinol. 4:1125-1135(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Testis.
    4. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. "Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme."
      Vekrellis K., Ye Z., Qiu W.Q., Walsh D., Hartley D., Chesneau V., Rosner M.R., Selkoe D.J.
      J. Neurosci. 20:1657-1665(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    8. "Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread."
      Li Q., Ali M.A., Cohen J.I.
      Cell 127:305-316(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH VZV GLYCOPROTEIN E.
    9. "The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for binding to insulin-degrading enzyme, a VZV receptor."
      Li Q., Krogmann T., Ali M.A., Tang W.-J., Cohen J.I.
      J. Virol. 81:8525-8532(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH VZV GLYCOPROTEIN E.
    10. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism."
      Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.
      Nature 443:870-874(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 42-1019 OF MUTANT GLN-111 IN COMPLEXES WITH ZINC IONS; IAPP; INSULIN; AMYLOID AND GLUCAGON, MUTAGENESIS OF GLU-111; SER-132; ASN-184; ASP-426; GLU-817; GLN-828 AND LYS-899, COFACTOR, SUBUNIT, ACTIVE SITE.
    14. "Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE."
      Im H., Manolopoulou M., Malito E., Shen Y., Zhao J., Neant-Fery M., Sun C.-Y., Meredith S.C., Sisodia S.S., Leissring M.A., Tang W.-J.
      J. Biol. Chem. 282:25453-25463(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 43-1018 OF MUTANT PHE-831 IN COMPLEX WITH ZINC IONS AND SUBSTRATE PEPTIDE, CATALYTIC ACTIVITY, ENZYME REGULATION, ATP-BINDING, SUBUNIT, MUTAGENESIS OF ASP-426 AND LYS-899, FUNCTION.
    15. "Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme."
      Malito E., Ralat L.A., Manolopoulou M., Tsay J.L., Wadlington N.L., Tang W.-J.
      Biochemistry 47:12822-12834(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 42-1019 OF MUTANT GLN-111 IN COMPLEX WITH BRADYKININ, FUNCTION, ENZYME REGULATION.

    Entry informationi

    Entry nameiIDE_HUMAN
    AccessioniPrimary (citable) accession number: P14735
    Secondary accession number(s): B2R721
    , B7ZAU2, D3DR35, Q5T5N2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: November 25, 2008
    Last modified: October 1, 2014
    This is version 150 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    ATP-binding induces a conformation change.

    Keywords - Technical termi

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

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3