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IDE insulin degrading enzyme [ Homo sapiens (human) ]

Gene ID: 3416, updated on 6-Sep-2021

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
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Genomic context

See IDE in Genome Data Viewer
Location:
10q23.33
Exon count:
34
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (92451684..92574093, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (94211441..94333850, 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

Associated conditions

Description Tests
Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.
GeneReviews: Not available
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
GeneReviews: Not available
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
GeneReviews: Not available

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: 403 organisms have orthologs with human gene IDE
  • Orthologs

Clone Names

  • FLJ35968

Gene Ontology Provided by GOA

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

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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_001165946.2NP_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, AL356128, 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_001322793.2NP_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_001322794.2NP_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_001322795.2NP_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 (1) summary
    COG1025
    Location:11917
    Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
  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 (1) summary
    COG1025
    Location:11917
    Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
  6. NM_001322797.2NP_001309726.1  insulin-degrading enzyme isoform 6

    Status: REVIEWED

    Source sequence(s)
    AK093287, AL356128
    UniProtKB/TrEMBL
    B3KSB8
    Related
    ENSP00000504053.1, ENST00000496903.5
    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_136399.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL356128
    Related
    ENST00000678844.1

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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..92574093 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    Related
    ENSP00000503025.1, ENST00000678715.1
  2. XM_017016188.1XP_016871677.1  insulin-degrading enzyme isoform X1

    Conserved Domains (1) summary
    COG1025
    Location:11917
    Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
  3. XM_017016189.1XP_016871678.1  insulin-degrading enzyme isoform X1

    Related
    ENST00000678458.1
    Conserved Domains (1) summary
    COG1025
    Location:11917
    Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
  4. XM_017016187.1XP_016871676.1  insulin-degrading enzyme isoform X1

    Conserved Domains (1) summary
    COG1025
    Location:11917
    Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]

RNA

  1. XR_945727.3 RNA Sequence

  2. XR_001747103.2 RNA Sequence

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