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

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; AllianceGenome:HGNC:5381
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: mouse all
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Genomic context

Location:: 10q23.33

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (92451684..92574093, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (93330970..93453429, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (94211441..94333850, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Correlation between insulin-degrading enzyme versus total tau and selected cytokines in patients with Alzheimer s disease compared to non-demented controls.
Title: Correlation between insulin-degrading enzyme versus total tau and selected cytokines in patients with Alzheimer´s disease compared to non-demented controls.
Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.
Title: Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.
Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid beta Oligomers by Insulin Degrading Enzyme.
Title: Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid β Oligomers by Insulin Degrading Enzyme.
Link of BIN1, CLU, and IDE Gene Polymorphisms with the Susceptibility of Alzheimer's Disease: Evidence from a Meta-analysis.
Title: Link of BIN1, CLU, and IDE Gene Polymorphisms with the Susceptibility of Alzheimer's Disease: Evidence from a Meta-analysis.
Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.
Title: Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.
Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations.
Title: Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations.
Degradation of Alzheimer's Amyloid-beta by a Catalytically Inactive Insulin-Degrading Enzyme.
Title: Degradation of Alzheimer's Amyloid-β by a Catalytically Inactive Insulin-Degrading Enzyme.
Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: effect of hypoxia and glucose deprivation.
Title: Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: effect of hypoxia and glucose deprivation.
Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.
Title: Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.
Of the 15 variants, 3 variants (rs13405728 in LHCGR; rs13429458 in THADA and rs2209972 IDE genes) were found to be associated with PCOS. The association was successfully replicated in an independent cohort. Insilico analysis categorized two variants (rs13429458-THADA and rs2209972-IDE genes) as deleterious.
Title: Pooled genetic analysis identifies variants that confer enhanced susceptibility to PCOS in Indian ethnicity.

Submit: New GeneRIF Correction See all GeneRIFs (115)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Ide (e-PCR), detects polymorphism
- UniSTS:506987

GDB:193867 (e-PCR)
- UniSTS:155775

D10S2141 (e-PCR)
- UniSTS:20873

RH44800 (e-PCR)
- UniSTS:39586

STS-T88914 (e-PCR)
- UniSTS:12466

IDE (e-PCR)
- UniSTS:502984

STS-D29519 (e-PCR)
- UniSTS:28873

WI-17525 (e-PCR)
- UniSTS:60139

RH80115 (e-PCR)
- UniSTS:92666

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction 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
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 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
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 hormone catabolic process	IBA Inferred from Biological aspect of Ancestor more info
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 peptide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
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	IMP Inferred from Mutant Phenotype 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 protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis involved in 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 symbiont entry into host cell	IEA Inferred from Electronic Annotation more info
involved_in ubiquitin recycling	IDA Inferred from Direct Assay more info	PubMed

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
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
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
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
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
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

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Preferred Names: insulin-degrading enzyme

Names: Abeta-degrading protease; insulin protease; insulinase

NP_001159418.1

EC 3.4.24.56

NP_001309722.1

EC 3.4.24.56

NP_001309723.1

EC 3.4.24.56

NP_001309724.1

EC 3.4.24.56

NP_001309725.1

EC 3.4.24.56

NP_001309726.1

EC 3.4.24.56

NP_001397903.1

EC 3.4.24.56

NP_004960.2

EC 3.4.24.56

XP_016871676.1

EC 3.4.24.56

XP_016871677.1

EC 3.4.24.56

XP_016871679.2

EC 3.4.24.56

XP_047281125.1

EC 3.4.24.56

XP_047281127.1

EC 3.4.24.56

XP_047281128.1

EC 3.4.24.56

XP_047281129.1

EC 3.4.24.56

XP_047281130.1

EC 3.4.24.56

XP_047281131.1

EC 3.4.24.56

XP_054221719.1

EC 3.4.24.56

XP_054221720.1

EC 3.4.24.56

XP_054221721.1

EC 3.4.24.56

XP_054221722.1

EC 3.4.24.56

XP_054221723.1

EC 3.4.24.56

XP_054221724.1

EC 3.4.24.56

XP_054221725.1

EC 3.4.24.56

XP_054221726.1

EC 3.4.24.56

XP_054221727.1

EC 3.4.24.56

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

NG_013012.1 RefSeqGene

Range

5003..127412

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001165946.2 → NP_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/TrEMBL

B7Z7W6

Related

ENSP00000360637.5, ENST00000371581.9

Conserved Domains (1) summary

cl25708
Location:2 → 403

Peptidase_M16; Insulinase (Peptidase family M16)
NM_001322793.2 → NP_001309722.1 insulin-degrading enzyme isoform 3

Status: REVIEWED

Source sequence(s)

AL356128

Consensus CDS

CCDS91301.1

UniProtKB/TrEMBL

A0A3B3ISG5, A0A7I2V3E3

Related

ENSP00000497272.1, ENST00000650060.2

Conserved Domains (4) summary

COG1025
Location:52 → 958

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]

pfam00675
Location:74 → 212

Peptidase_M16; Insulinase (Peptidase family M16)

pfam05193
Location:238 → 416

Peptidase_M16_C; Peptidase M16 inactive domain

pfam16187
Location:422 → 703

Peptidase_M16_M; Middle or third domain of peptidase_M16
NM_001322794.2 → NP_001309723.1 insulin-degrading enzyme isoform 4

Status: REVIEWED

Source sequence(s)

AL356128

UniProtKB/TrEMBL

A0A7I2V3E3

Conserved Domains (4) summary

COG1025
Location:52 → 919

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]

pfam00675
Location:74 → 212

Peptidase_M16; Insulinase (Peptidase family M16)

pfam05193
Location:218 → 377

Peptidase_M16_C; Peptidase M16 inactive domain

pfam16187
Location:383 → 664

Peptidase_M16_M; Middle or third domain of peptidase_M16
NM_001322795.2 → NP_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

UniProtKB/TrEMBL

A0A7I2V3E3

Conserved Domains (1) summary

COG1025
Location:11 → 917

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
NM_001322796.1 → NP_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

UniProtKB/TrEMBL

A0A7I2V3E3

Conserved Domains (1) summary

COG1025
Location:11 → 917

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
NM_001322797.2 → NP_001309726.1 insulin-degrading enzyme isoform 6

Status: REVIEWED

Source sequence(s)

AK093287, AL356128

Consensus CDS

CCDS91299.1

UniProtKB/TrEMBL

B3KSB8, B7Z7W6

Related

ENSP00000504053.1, ENST00000496903.5

Conserved Domains (2) summary

pfam05193
Location:151 → 334

Peptidase_M16_C; Peptidase M16 inactive domain

pfam16187
Location:1 → 148

Peptidase_M16_M; Middle or third domain of peptidase_M16
NM_001410974.1 → NP_001397903.1 insulin-degrading enzyme isoform 7

Status: REVIEWED

Source sequence(s)

AL356128

Consensus CDS

CCDS91300.1

UniProtKB/TrEMBL

A0A7I2V2P6

Related

ENSP00000503025.1, ENST00000678715.1
NM_004969.4 → NP_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

B2R721, B7ZAU2, D3DR35, P14735, Q5T5N2

UniProtKB/TrEMBL

A0A7I2V3E3

Related

ENSP00000265986.6, ENST00000265986.11

Conserved Domains (1) summary

COG1025
Location:52 → 958

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]

RNA

NR_136399.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL356128

Related

ENST00000678844.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

92451684..92574093 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047425171.1 → XP_047281127.1 insulin-degrading enzyme isoform X3
XM_017016190.2 → XP_016871679.2 insulin-degrading enzyme isoform X2
XM_047425169.1 → XP_047281125.1 insulin-degrading enzyme isoform X1
XM_017016188.2 → XP_016871677.1 insulin-degrading enzyme isoform X3

UniProtKB/TrEMBL

A0A7I2V3E3

Conserved Domains (1) summary

COG1025
Location:11 → 917

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
XM_017016187.2 → XP_016871676.1 insulin-degrading enzyme isoform X3

UniProtKB/TrEMBL

A0A7I2V3E3

Related

ENST00000678458.1

Conserved Domains (1) summary

COG1025
Location:11 → 917

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
XM_047425174.1 → XP_047281130.1 insulin-degrading enzyme isoform X6

UniProtKB/TrEMBL

A0A7I2V373

Related

ENSP00000503274.1, ENST00000677434.1
XM_047425172.1 → XP_047281128.1 insulin-degrading enzyme isoform X4
XM_047425175.1 → XP_047281131.1 insulin-degrading enzyme isoform X7
XM_047425173.1 → XP_047281129.1 insulin-degrading enzyme isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

93330970..93453429 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054365746.1 → XP_054221721.1 insulin-degrading enzyme isoform X3
XM_054365748.1 → XP_054221723.1 insulin-degrading enzyme isoform X1
XM_054365744.1 → XP_054221719.1 insulin-degrading enzyme isoform X2
XM_054365747.1 → XP_054221722.1 insulin-degrading enzyme isoform X3
XM_054365745.1 → XP_054221720.1 insulin-degrading enzyme isoform X3
XM_054365751.1 → XP_054221726.1 insulin-degrading enzyme isoform X6

UniProtKB/TrEMBL

A0A7I2V373
XM_054365749.1 → XP_054221724.1 insulin-degrading enzyme isoform X4
XM_054365752.1 → XP_054221727.1 insulin-degrading enzyme isoform X7
XM_054365750.1 → XP_054221725.1 insulin-degrading enzyme isoform X5