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IDE insulin degrading enzyme [ Homo sapiens (human) ]

Gene ID: 3416, updated on 8-Oct-2018

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; Vega:OTTHUMG00000018759
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 current GRCh38.p12 (GCF_000001405.38) 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat'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

Pathways from BioSystems

  • Alzheimer's disease, organism-specific biosystem (from KEGG)
    Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimer's disease, conserved biosystem (from KEGG)
    Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
    Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
  • Deubiquitination, organism-specific biosystem (from REACTOME)
    Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Post-translational protein modification, organism-specific biosystem (from REACTOME)
    Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
  • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
    Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

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
 
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 
peptide binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
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 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 
bradykinin catabolic process IDA
Inferred from Direct Assay
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 
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
 
positive regulation of protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
positive regulation of protein oligomerization IDA
Inferred from Direct Assay
more info
PubMed 
protein heterooligomerization IEA
Inferred from Electronic Annotation
more info
 
protein homooligomerization IDA
Inferred from Direct Assay
more info
PubMed 
protein homotetramerization IEA
Inferred from Electronic Annotation
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 
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
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
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
 
cytosolic proteasome complex IEA
Inferred from Electronic Annotation
more info
 
extracellular space IDA
Inferred from Direct Assay
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 
plasma membrane IEA
Inferred from Electronic Annotation
more info
 

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
    5001..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_004969.3NP_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, OTTHUMP00000020097, ENST00000265986.10, OTTHUMT00000049393
    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 Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p12 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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