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    IDE insulin degrading enzyme [ Homo sapiens (human) ]

    Gene ID: 3416, updated on 13-Mar-2020

    Summary

    Official Symbol
    IDEprovided by HGNC
    Official Full Name
    insulin degrading enzymeprovided by HGNC
    Primary source
    HGNC:HGNC:5381
    See related
    Ensembl:ENSG00000119912 MIM:146680
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    INSULYSIN
    Summary
    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]
    Expression
    Ubiquitous expression in skin (RPKM 17.4), testis (RPKM 9.9) and 25 other tissues See more
    Orthologs

    Genomic context

    See IDE in Genome Data Viewer
    Location:
    10q23.33
    Exon count:
    34
    Annotation release Status Assembly Chr Location
    109.20200228 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (92451684..92574095, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (94211441..94333852, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene membrane associated ring-CH-type finger 5 Neighboring gene RNY3 pseudogene 12 Neighboring gene microtubule affinity regulating kinase 2 pseudogene 9 Neighboring gene ribosomal protein L11 pseudogene 4 Neighboring gene kinesin family member 11 Neighboring gene RNA, 7SL, cytoplasmic 644, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    NHGRI GWAS Catalog

    Description
    Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.
    NHGRI GWA Catalog
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
    NHGRI GWA Catalog
    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
    NHGRI GWA Catalog

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    • Homologs of the IDE gene: The IDE gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
    • Orthologs from Annotation Pipeline: 300 organisms have orthologs with human gene IDE
    • Orthologs

    Clone Names

    • FLJ35968

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    ATPase activity IEA
    Inferred from Electronic Annotation
    more info
     
    amyloid-beta binding IEA
    Inferred from Electronic Annotation
    more info
     
    beta-endorphin binding IEA
    Inferred from Electronic Annotation
    more info
     
    endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    metalloendopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    peptide binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
     
    ubiquitin-dependent protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    zinc ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    amyloid-beta clearance IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    amyloid-beta clearance ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    amyloid-beta clearance by cellular catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    amyloid-beta clearance by cellular catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    amyloid-beta metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    amyloid-beta metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antigen processing and presentation of endogenous peptide antigen via MHC class I IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    bradykinin catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    determination of adult lifespan IDA
    Inferred from Direct Assay
    more info
    PubMed 
    hormone catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    hormone catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of proteolysis IEA
    Inferred from Electronic Annotation
    more info
     
    peptide catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    peptide catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein catabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    protein targeting to peroxisome TAS
    Traceable Author Statement
    more info
     
    proteolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    proteolysis involved in cellular protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    proteolysis involved in cellular protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of aerobic respiration IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    ubiquitin recycling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    viral entry into host cell IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    basolateral plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cell IEA
    Inferred from Electronic Annotation
    more info
     
    cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell surface ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    cytosolic proteasome complex IEA
    Inferred from Electronic Annotation
    more info
     
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular exosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular space ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    extracellular space TAS
    Traceable Author Statement
    more info
    PubMed 
    mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peroxisomal matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    peroxisomal matrix TAS
    Traceable Author Statement
    more info
     
    peroxisome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peroxisome TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    insulin-degrading enzyme
    Names
    Abeta-degrading protease
    insulin protease
    insulinase
    NP_001159418.1
    NP_001309722.1
    NP_001309723.1
    NP_001309724.1
    NP_001309725.1
    NP_001309726.1
    NP_004960.2
    XP_016871676.1
    XP_016871677.1
    XP_016871678.1
    XP_016871679.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013012.1 RefSeqGene

      Range
      5003..127412
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001165946.1NP_001159418.1  insulin-degrading enzyme isoform 2

      See identical proteins and their annotated locations for NP_001159418.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple exons that are present in the 5' end of variant 1. Variant 2 contains a novel exon at its 5' end and begins translation from a downstream in-frame start codon, compared to variant 1. The encoded protein (isoform 2) lacks 555 amino acids from the N-terminus of isoform 1 but is identical to its C-terminal 464 amino acids. Compared to isoform 1, isoform 2 lacks two of three M16 peptidase domains and the N-terminal catalytic domain. The C-terminus of isoform 2 retains the oligomerization domain and peroxisomal targeting sequence present in isoform 1.
      Source sequence(s)
      AK316407, BX648462, CF780766, CK824565, DA879845, DB445060
      Consensus CDS
      CCDS53554.1
      UniProtKB/Swiss-Prot
      P14735
      Related
      ENSP00000360637.5, ENST00000371581.9
      Conserved Domains (1) summary
      cl25708
      Location:2403
      Peptidase_M16; Insulinase (Peptidase family M16)
    2. NM_001322793.1NP_001309722.1  insulin-degrading enzyme isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL356128
      Related
      ENSP00000497272.1, ENST00000650060.1
      Conserved Domains (4) summary
      COG1025
      Location:52958
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:74212
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:238416
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:422703
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    3. NM_001322794.1NP_001309723.1  insulin-degrading enzyme isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL356128
      Conserved Domains (4) summary
      COG1025
      Location:52919
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:74212
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:218377
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:383664
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    4. NM_001322795.1NP_001309724.1  insulin-degrading enzyme isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) and variant 6 both encode isoform 5.
      Source sequence(s)
      AL356128
      Conserved Domains (4) summary
      COG1025
      Location:11917
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:33171
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:197375
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:381662
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    5. NM_001322796.1NP_001309725.1  insulin-degrading enzyme isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) and variant 5 both encode isoform (5).
      Source sequence(s)
      AL356128, BX648462
      Conserved Domains (4) summary
      COG1025
      Location:11917
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:33171
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:197375
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:381662
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    6. NM_001322797.1NP_001309726.1  insulin-degrading enzyme isoform 6

      Status: REVIEWED

      Source sequence(s)
      AK093287, AL356128
      UniProtKB/TrEMBL
      B3KSB8
      Conserved Domains (2) summary
      pfam05193
      Location:151334
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:1148
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    7. NM_004969.4NP_004960.2  insulin-degrading enzyme isoform 1

      See identical proteins and their annotated locations for NP_004960.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest protein (isoform 1). Alternative translation initiation of this transcript variant produces an isoform that lacks 41 aa from the N-terminus and, purportedly, lacks an N-terminal mitochondrial targeting sequence.
      Source sequence(s)
      BC096337, BX648462, CF780766, CK824565, DA879845, DB219527
      Consensus CDS
      CCDS7421.1
      UniProtKB/Swiss-Prot
      P14735
      Related
      ENSP00000265986.6, ENST00000265986.11
      Conserved Domains (1) summary
      COG1025
      Location:52958
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]

    RNA

    1. NR_136399.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL356128

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p13 Primary Assembly

      Range
      92451684..92574095 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017016190.1XP_016871679.1  insulin-degrading enzyme isoform X2

    2. XM_017016188.1XP_016871677.1  insulin-degrading enzyme isoform X1

      Conserved Domains (4) summary
      COG1025
      Location:11917
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:33171
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:197375
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:381662
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    3. XM_017016189.1XP_016871678.1  insulin-degrading enzyme isoform X1

      Conserved Domains (4) summary
      COG1025
      Location:11917
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:33171
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:197375
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:381662
      Peptidase_M16_M; Middle or third domain of peptidase_M16
    4. XM_017016187.1XP_016871676.1  insulin-degrading enzyme isoform X1

      Conserved Domains (4) summary
      COG1025
      Location:11917
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:33171
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:197375
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:381662
      Peptidase_M16_M; Middle or third domain of peptidase_M16

    RNA

    1. XR_945727.3 RNA Sequence

    2. XR_001747103.2 RNA Sequence

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