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Aliases for IDE Gene

Aliases for IDE Gene

  • Insulin Degrading Enzyme 2 3 5
  • Insulysin 2 3 4
  • Insulin-Degrading Enzyme 2 3
  • Abeta-Degrading Protease 3 4
  • Insulin Protease 3 4
  • EC 3.4.24.56 4 61
  • Insulinase 3 4
  • EC 3.4.24 61

External Ids for IDE Gene

Previous GeneCards Identifiers for IDE Gene

  • GC10M093095
  • GC10M093435
  • GC10M094342
  • GC10M093878
  • GC10M094201
  • GC10M087837
  • GC10M094211

Summaries for IDE Gene

Entrez Gene Summary for IDE Gene

  • This gene encodes a zinc metallopeptidase that degrades intracellular insulin, and thereby terminates insulins activity, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. The preferential affinity of this enzyme for insulin results in insulin-mediated inhibition of the degradation of other peptides such as beta-amyloid. Deficiencies in this protein's function are associated with Alzheimer's disease and type 2 diabetes mellitus but mutations in this gene have not been shown to be causitive for these diseases. This protein localizes primarily to the cytoplasm but in some cell types localizes to the extracellular space, cell membrane, peroxisome, and mitochondrion. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but have not been experimentally verified.[provided by RefSeq, Sep 2009]

GeneCards Summary for IDE Gene

IDE (Insulin Degrading Enzyme) is a Protein Coding gene. Diseases associated with IDE include Alzheimer Disease and Alzheimer Disease-2. Among its related pathways are Deubiquitination and A-beta Pathways: Uptake and Degradation. GO annotations related to this gene include protein homodimerization activity and ATPase activity. An important paralog of this gene is NRDC.

UniProtKB/Swiss-Prot for IDE Gene

  • 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.

  • (Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).

Gene Wiki entry for IDE Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IDE Gene

Genomics for IDE Gene

Regulatory Elements for IDE Gene

Enhancers for IDE Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH10G092688 1.6 Ensembl ENCODE dbSUPER 11.9 -119.5 -119516 10.1 HDGF PKNOX1 FOXA2 MLX ARNT AGO1 ARID4B SIN3A FEZF1 DMAP1 KIF11 HHEX IDE BTAF1 TNKS2 EIF2S2P3 GC10M092666
GH10G092833 1.4 FANTOM5 Ensembl ENCODE dbSUPER 10.7 -260.5 -260474 2.3 PAF1 JUN USF2 MAX CEBPG ZNF121 JUND ATF3 THRAP3 FOS KIF11 IDE MARCH5 EXOC6 GC10M092798
GH10G092644 1.2 Ensembl ENCODE 11.5 -70.5 -70520 1.0 PKNOX1 ARID4B SIN3A FEZF1 ZNF2 YY1 ZNF121 GATA2 FOS REST HHEX KIF11 IDE RN7SL644P GC10P092612
GH10G092544 0.6 ENCODE 12.5 +29.5 29496 0.5 EGR1 CEBPA IKZF1 HMBOX1 MAX REST IKZF2 SPI1 IDE KIF11 GC10M092559 GC10M092442
GH10G092572 1.1 ENCODE 6 +0.3 310 3.2 PKNOX1 CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143 FOS BTAF1 RPL17P34 MARK2P9 IDE EIF2S2P3 GC10M092559
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around IDE on UCSC Golden Path with GeneCards custom track

Promoters for IDE Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000031664 295 2401 PKNOX1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143 FOS ZNF263

Genomic Location for IDE Gene

Chromosome:
10
Start:
92,451,684 bp from pter
End:
92,574,095 bp from pter
Size:
122,412 bases
Orientation:
Minus strand

Genomic View for IDE Gene

Genes around IDE on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IDE Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IDE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IDE Gene

Proteins for IDE Gene

  • Protein details for IDE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P14735-IDE_HUMAN
    Recommended name:
    Insulin-degrading enzyme
    Protein Accession:
    P14735
    Secondary Accessions:
    • B2R721
    • B7ZAU2
    • D3DR35
    • Q5T5N2

    Protein attributes for IDE Gene

    Size:
    1019 amino acids
    Molecular mass:
    117968 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer. Can form higher oligomers.
    • (Microbial infection) 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 (PubMed:17055432, PubMed:17553876).
    Miscellaneous:
    • ATP-binding induces a conformation change.

    Three dimensional structures from OCA and Proteopedia for IDE Gene

    Alternative splice isoforms for IDE Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IDE Gene

Selected DME Specific Peptides for IDE Gene

P14735:
  • KVLLISDP
  • EDKREYRGLELANGIKVLL
  • EHMLFLGT
  • GALDRFAQFF
  • YYSSNLM
  • HLIGHEGPGSLLSELK
  • KIVPIKDIR

Post-translational modifications for IDE Gene

  • The N-terminus is blocked.
  • Ubiquitination at isoforms=192, isoforms=308, posLast=884884, isoforms=2929, isoforms=2938, and isoforms=21018
  • Modification sites at PhosphoSitePlus

Antibody Products

Domains & Families for IDE Gene

Graphical View of Domain Structure for InterPro Entry

P14735

UniProtKB/Swiss-Prot:

IDE_HUMAN :
  • The SlyX motif may be involved in the non-conventional secretion of the protein.
  • Belongs to the peptidase M16 family.
Domain:
  • The SlyX motif may be involved in the non-conventional secretion of the protein.
Family:
  • Belongs to the peptidase M16 family.
genes like me logo Genes that share domains with IDE: view

No data available for Gene Families for IDE Gene

Function for IDE Gene

Molecular function for IDE Gene

GENATLAS Biochemistry:
insulin degrading enzyme,cytosolic metalloproteinase (110kDa)
UniProtKB/Swiss-Prot CatalyticActivity:
Degradation of insulin, glucagon and other polypeptides. No action on proteins.
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Function:
(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).

Enzyme Numbers (IUBMB) for IDE Gene

Gene Ontology (GO) - Molecular Function for IDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 beta-amyloid binding IEA --
GO:0001618 virus receptor activity IEA --
GO:0001948 glycoprotein binding IPI 17055432
GO:0003824 catalytic activity IEA --
GO:0004222 metalloendopeptidase activity IDA 17051221
genes like me logo Genes that share ontologies with IDE: view
genes like me logo Genes that share phenotypes with IDE: view

Animal Models for IDE Gene

MGI Knock Outs for IDE:
  • Ide tm1a(EUCOMM)Wtsi

Animal Model Products

  • Taconic Biosciences Mouse Models for IDE

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for IDE Gene

Localization for IDE Gene

Subcellular locations from UniProtKB/Swiss-Prot for IDE Gene

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

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IDE gene
Compartment Confidence
extracellular 5
mitochondrion 5
peroxisome 5
nucleus 5
cytosol 5
plasma membrane 4
lysosome 2
endosome 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for IDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 9830016
GO:0005634 NOT nucleus IDA 18226493
GO:0005737 cytoplasm IEA,IDA 9231799
GO:0005739 mitochondrion IDA 15285718
genes like me logo Genes that share ontologies with IDE: view

Pathways & Interactions for IDE Gene

genes like me logo Genes that share pathways with IDE: view

Pathways by source for IDE Gene

1 BioSystems pathway for IDE Gene
1 KEGG pathway for IDE Gene
1 Qiagen pathway for IDE Gene

Gene Ontology (GO) - Biological Process for IDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IDA 20082125
GO:0008152 metabolic process IEA --
GO:0008286 insulin receptor signaling pathway NAS 3059494
GO:0008340 determination of adult lifespan IDA 18448515
GO:0010815 bradykinin catabolic process IDA 17613531
genes like me logo Genes that share ontologies with IDE: view

No data available for SIGNOR curated interactions for IDE Gene

Drugs & Compounds for IDE Gene

(19) Drugs for IDE Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bacitracin Approved, Vet_approved Pharma Target, inhibitor 40
Zinc Approved Pharma 2296
Insulin Human Approved, Investigational Pharma Target 0
Insulin Pork Approved Pharma Target 0

(9) Additional Compounds for IDE Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IDE: view

Transcripts for IDE Gene

Unigene Clusters for IDE Gene

Insulin-degrading enzyme:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IDE Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^ 26 ^
SP1: - -
SP2: -
SP3:

ExUns: 27 ^ 28 ^ 29a · 29b
SP1:
SP2:
SP3:

Relevant External Links for IDE Gene

GeneLoc Exon Structure for
IDE
ECgene alternative splicing isoforms for
IDE

Expression for IDE Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for IDE Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for IDE Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x4.2).

Protein differential expression in normal tissues from HIPED for IDE Gene

This gene is overexpressed in Lymph node (9.0) and Stomach (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for IDE Gene



Protein tissue co-expression partners for IDE Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of IDE Gene:

IDE

SOURCE GeneReport for Unigene cluster for IDE Gene:

Hs.500546

Evidence on tissue expression from TISSUES for IDE Gene

  • Nervous system(3.1)
  • Liver(2.7)
  • Muscle(2.4)
  • Blood(2)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with IDE: view

Primer Products

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for IDE Gene

Orthologs for IDE Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for IDE Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IDE 34 35
  • 99.8 (n)
cow
(Bos Taurus)
Mammalia IDE 34 35
  • 94.41 (n)
dog
(Canis familiaris)
Mammalia IDE 34 35
  • 94.24 (n)
oppossum
(Monodelphis domestica)
Mammalia IDE 35
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia IDE 35
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ide 34
  • 89.7 (n)
mouse
(Mus musculus)
Mammalia Ide 34 16 35
  • 89.01 (n)
chicken
(Gallus gallus)
Aves -- 35
  • 98 (a)
OneToMany
-- 35
  • 92 (a)
OneToMany
IDE 34
  • 82.7 (n)
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 88 (a)
OneToMany
-- 35
  • 87 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia ide 34
  • 78.88 (n)
zebrafish
(Danio rerio)
Actinopterygii ide 34 35
  • 76.48 (n)
Dr.5554 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010351 34
  • 53.65 (n)
fruit fly
(Drosophila melanogaster)
Insecta Ide 36 34 35
  • 52.85 (n)
worm
(Caenorhabditis elegans)
Secernentea F44E7.4 34 35
  • 49.98 (n)
C28F5.4 36 35
  • 47 (a)
C02G6.2 36 35
  • 41 (a)
C02G6.1 36 35
  • 38 (a)
Y70C5C.1 36 35
  • 33 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E05105g 34
  • 49.37 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes STE23 34 35 37
  • 49.2 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AER053C 34
  • 47.3 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G41790 34
  • 49.34 (n)
rice
(Oryza sativa)
Liliopsida Os07g0570300 34
  • 49.48 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 55 (a)
OneToMany
-- 35
  • 52 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU00481 34
  • 49.14 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes mug138 34
  • 47.94 (n)
Species where no ortholog for IDE was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for IDE Gene

ENSEMBL:
Gene Tree for IDE (if available)
TreeFam:
Gene Tree for IDE (if available)

Paralogs for IDE Gene

Paralogs for IDE Gene

(1) SIMAP similar genes for IDE Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with IDE: view

Variants for IDE Gene

Sequence variations from dbSNP and Humsavar for IDE Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type
rs1000015730 -- 92,559,885(+) GGCAC(A/G)TGCCT intron-variant
rs1000017365 -- 92,514,432(+) CTTTG(C/T)CCTTT intron-variant
rs1000026378 -- 92,513,274(+) TGCAG(A/C)CTCCA intron-variant
rs1000071119 -- 92,560,234(+) TTAAC(C/T)GTGTA intron-variant
rs1000072128 -- 92,514,616(+) ATTTT(C/T)TTTGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for IDE Gene

Variant ID Type Subtype PubMed ID
dgv1349n54 CNV loss 21841781
esv3431710 CNV insertion 20981092
esv3546688 CNV deletion 23714750
esv3624226 CNV loss 21293372
nsv1046258 CNV gain 25217958
nsv1122547 CNV deletion 24896259
nsv1127132 CNV deletion 24896259
nsv508600 CNV deletion 20534489

Variation tolerance for IDE Gene

Residual Variation Intolerance Score: 3.78% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.75; 33.09% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for IDE Gene

Human Gene Mutation Database (HGMD)
IDE
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IDE

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IDE Gene

Disorders for IDE Gene

MalaCards: The human disease database

(3) MalaCards diseases for IDE Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • alzheimer disease, late-onset
alzheimer disease-2
  • alzheimer's disease 2
diabetes mellitus, noninsulin-dependent
  • diabetes, type 2
- elite association - COSMIC cancer census association via MalaCards
Search IDE in MalaCards View complete list of genes associated with diseases

Relevant External Links for IDE

Genetic Association Database (GAD)
IDE
Human Genome Epidemiology (HuGE) Navigator
IDE
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
IDE
genes like me logo Genes that share disorders with IDE: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IDE Gene

Publications for IDE Gene

  1. Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes. (PMID: 2293021) Affholter J.A. … Roth R.A. (Mol. Endocrinol. 1990) 2 3 4 22 64
  2. Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Abeta, and Alzheimer's disease. (PMID: 20098734) Carrasquillo M.M. … Morgan K. (PLoS ONE 2010) 3 22 46 64
  3. Promoter polymorphisms which modulate insulin degrading enzyme expression may increase susceptibility to Alzheimer's disease. (PMID: 18996360) Zuo X. … Jia J. (Brain Res. 2009) 3 22 46 64
  4. Variants in the insulin-degrading enzyme gene are associated with metabolic syndrome in Chinese elders. (PMID: 19592050) Lu X. … Shi X. (Metab. Clin. Exp. 2009) 3 22 46 64
  5. Polymorphisms within insulin-degrading enzyme (IDE) gene determine insulin metabolism and risk of type 2 diabetes. (PMID: 19809796) Rudovich N. … Pfeiffer A.F. (J. Mol. Med. 2009) 3 22 46 64

Products for IDE Gene

Sources for IDE Gene

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