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IDE insulin-degrading enzyme [ Homo sapiens (human) ]

Gene ID: 3416, updated on 5-Apr-2015
Official Symbol
IDEprovided by HGNC
Official Full Name
insulin-degrading enzymeprovided by HGNC
Primary source
HGNC:HGNC:5381
See related
Ensembl:ENSG00000119912; HPRD:00894; 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]
Orthologs
See IDE in MapViewer
Location:
10q23-q25
Exon count:
28
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 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 finger (C3HC4) 5 Neighboring gene MAP/microtubule affinity-regulating kinase 2 pseudogene 9 Neighboring gene uncharacterized LOC105378434 Neighboring gene ribosomal protein L11 pseudogene 4 Neighboring gene kinesin family member 11 Neighboring gene eukaryotic translation initiation factor 2, subunit 2 beta pseudogene 3

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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
  • 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...
Products Interactant Other Gene Complex Source Pubs Description

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
 
beta-amyloid binding IEA
Inferred from Electronic Annotation
more info
 
beta-endorphin binding IEA
Inferred from Electronic Annotation
more info
 
glycoprotein binding IPI
Inferred from Physical Interaction
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 
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 
receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin binding IPI
Inferred from Physical Interaction
more info
PubMed 
zinc ion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
beta-amyloid 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 IEA
Inferred from Electronic Annotation
more info
 
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 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
 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis involved in cellular protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
viral process 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
 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosolic proteasome complex IEA
Inferred from Electronic Annotation
more info
 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
NOT nucleus IDA
Inferred from Direct Assay
more info
PubMed 
peroxisomal matrix IEA
Inferred from Electronic Annotation
more info
 
peroxisome IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
insulin-degrading enzyme
Names
insulin-degrading enzyme
Abeta-degrading protease
insulin protease
insulinase
NP_001159418.1
NP_004960.2

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, ENST00000371581
    Conserved Domains (1) summary
    pfam05193
    Location:151334
    Peptidase_M16_C; Peptidase M16 inactive domain
  2. 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) represents the longer transcript and encodes the longer 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, OTTHUMP00000020097, ENST00000265986, OTTHUMT00000049393
    Conserved Domains (3) 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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p2 Primary Assembly

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

mRNA and Protein(s)

  1. XM_005269766.2XP_005269823.1  

    Conserved Domains (3) 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
  2. XM_005269769.3XP_005269826.1  

    Conserved Domains (2) summary
    pfam00675
    Location:74212
    Peptidase_M16; Insulinase (Peptidase family M16)
    pfam05193
    Location:238416
    Peptidase_M16_C; Peptidase M16 inactive domain

RNA

  1. XR_945727.1 RNA Sequence

Alternate CHM1_1.1

Genomic

  1. NC_018921.2 Alternate CHM1_1.1

    Range
    94493176..94615858
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)