Ide insulin degrading enzyme [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Ideprovided by RGD
Official Full Name: insulin degrading enzymeprovided by RGD
Primary source: RGD:2861
See related: EnsemblRapid:ENSRNOG00000016833 AllianceGenome:RGD:2861
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: INSDEGM
Summary: Enables several functions, including ATP binding activity; ATP hydrolysis activity; and amyloid-beta binding activity. Involved in several processes, including amyloid-beta clearance by cellular catabolic process; hormone catabolic process; and negative regulation of proteolysis. Located in cell surface; extracellular space; and peroxisomal matrix. Part of cytosolic proteasome complex. Used to study Alzheimer's disease and type 2 diabetes mellitus. Biomarker of Alzheimer's disease and metabolic dysfunction-associated steatotic liver disease. Human ortholog(s) of this gene implicated in type 2 diabetes mellitus. Orthologous to human IDE (insulin degrading enzyme). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Kidney (RPKM 193.2), Muscle (RPKM 191.3) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 1q53

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	1	NC_086019.1 (244415495..244516925, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	1	NC_051336.1 (235002984..235102448, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	1	NC_005100.4 (255914465..256014168, complement)

Chromosome 1 - NC_086019.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

GLP-1R regulates cell growth, at least partially, through regulating cAMP/PKA/IDE signaling pathway in ABETA(1-42)-treated PC12 cells.
Title: GLP-1 receptor regulates cell growth through regulating IDE expression level in Aβ1-42-treated PC12 cells.
data suggest that insulin deprivation, rather than high glucose, is a significant determinant of IDE regulation; as evidence indicates potential roles for IDE in diabetes and Alzheimer's disease, understanding the mechanisms regulating IDE expression may be important in developing new treatment strategies
Title: Insulin deprivation decreases insulin degrading enzyme levels in primary cultured cortical neurons and in the cerebral cortex of rats with streptozotocin-induced diabetes.
This study concluded that vitamin D3 ameliorated insulin resistance and hyperinsulinemia in diabetic rat model received high fructose water through reduction of insulin-degrading enzyme and activation of insulin receptor phosphorylation.
Title: Vitamin D3 intake as regulator of insulin degrading enzyme and insulin receptor phosphorylation in diabetic rats.
Ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Abeta was reported in Azheimer disease patients.
Title: Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.
Insulin-degrading enzyme is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate.
Title: Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme.
Proteolytically inactive insulin-degrading enzyme inhibits amyloid formation yielding non-neurotoxic abeta peptide aggregates.
Title: Proteolytically inactive insulin-degrading enzyme inhibits amyloid formation yielding non-neurotoxic aβ peptide aggregates.
Ginsenoside Rg1 decreases Abeta(1-42) level by upregulating PPARgamma and IDE expression in the hippocampus of a rat model of Alzheimer's disease.
Title: Ginsenoside Rg1 decreases Aβ(1-42) level by upregulating PPARγ and IDE expression in the hippocampus of a rat model of Alzheimer's disease.
IDE-Met(1) links the mitochondrial biogenesis pathway with mitAbeta levels and organelle functionality.
Title: Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality.
Mutation of each cysteine residue individually revealed cysteine 904 as the key residue required for maximal activity and polyanion activation, although other cysteines affect polyanion binding to a lesser extent.
Title: Cysteine 904 is required for maximal insulin degrading enzyme activity and polyanion activation.
role played by somatostatin in preventing Abeta accumulation by partially restoring IDE activity
Title: Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

BE121412 (e-PCR)
- UniSTS:248093

RH135430 (e-PCR)
- UniSTS:218707

AU027754 (e-PCR)
- UniSTS:112998

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

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP binding	IPI Inferred from Physical Interaction more info	PubMed
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-endorphin binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables insulin binding	IEA Inferred from Electronic Annotation more info
enables insulin binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables insulin binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
enables metalloendopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables peptidase activity	TAS Traceable Author Statement more info	PubMed
enables peptide binding	IEA Inferred from Electronic Annotation more info
enables peptide binding	ISO Inferred from Sequence Orthology more info
enables peptide hormone binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta clearance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within amyloid-beta clearance	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta clearance	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta clearance by cellular catabolic process	IEA Inferred from Electronic Annotation 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	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid-beta metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid-beta metabolic process	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I	IEA Inferred from Electronic Annotation more info
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I	ISO Inferred from Sequence Orthology more info
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I	ISS Inferred from Sequence or Structural Similarity more info
involved_in bradykinin catabolic process	IEA Inferred from Electronic Annotation more info
involved_in bradykinin catabolic process	ISO Inferred from Sequence Orthology more info
involved_in bradykinin catabolic process	ISS Inferred from Sequence or Structural Similarity more info
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 hormone catabolic process	IEA Inferred from Electronic Annotation more info
involved_in hormone catabolic process	ISO Inferred from Sequence Orthology more info
involved_in insulin catabolic process	IEA Inferred from Electronic Annotation more info
involved_in insulin catabolic process	ISO Inferred from Sequence Orthology more info
involved_in insulin catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in insulin metabolic process	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor recycling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide catabolic process	IEA Inferred from Electronic Annotation more info
involved_in peptide catabolic process	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptide catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
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	IEA Inferred from Electronic Annotation more info
involved_in proteolysis involved in protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis involved in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of aerobic respiration	IEA Inferred from Electronic Annotation more info
involved_in regulation of aerobic respiration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in ubiquitin recycling	IEA Inferred from Electronic Annotation more info
involved_in ubiquitin recycling	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
part_of cytosolic proteasome complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in endosome lumen	ISO Inferred from Sequence Orthology more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in extracellular exosome	ISO Inferred from Sequence Orthology more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
NOT located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in peroxisomal matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in peroxisomal matrix	IDA Inferred from Direct Assay more info	PubMed
located_in peroxisome	IEA Inferred from Electronic Annotation more info
located_in peroxisome	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: insulin-degrading enzyme

Names: insulin protease; insulinase; insulysin

NP_037291.1

EC 3.4.24.56

XP_006231375.1

EC 3.4.24.56

XP_038958052.1

EC 3.4.24.56

XP_038958055.1

EC 3.4.24.56

XP_063138239.1

EC 3.4.24.56

XP_063138241.1

EC 3.4.24.56

XP_063138244.1

EC 3.4.24.56

XP_063138247.1

EC 3.4.24.56

XP_063138251.1

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.

mRNA and Protein(s)

NM_013159.2 → NP_037291.1 insulin-degrading enzyme

See identical proteins and their annotated locations for NP_037291.1

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000001

UniProtKB/Swiss-Prot

P35559

UniProtKB/TrEMBL

A0A0G2K7Q7, A6I165

Related

ENSRNOP00000074304.3, ENSRNOT00000085303.3

Conserved Domains (1) summary

COG1025
Location:54 → 958

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

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086019.1 Reference GRCr8

Range

244415495..244516925 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006231313.5 → XP_006231375.1 insulin-degrading enzyme isoform X3

UniProtKB/TrEMBL

A0A0G2K7Q7, A0A8I6A860

Related

ENSRNOP00000088595.1, ENSRNOT00000119683.2

Conserved Domains (4) summary

COG1025
Location:54 → 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
XM_063282171.1 → XP_063138241.1 insulin-degrading enzyme isoform X2

UniProtKB/TrEMBL

A0A0G2K7Q7
XM_063282169.1 → XP_063138239.1 insulin-degrading enzyme isoform X1

UniProtKB/TrEMBL

A0A0G2K7Q7
XM_063282181.1 → XP_063138251.1 insulin-degrading enzyme isoform X8

UniProtKB/TrEMBL

A0A0G2K7Q7
XM_039102127.2 → XP_038958055.1 insulin-degrading enzyme isoform X7

UniProtKB/TrEMBL

A0A0G2K7Q7, A0A8I6A841

Related

ENSRNOP00000087605.1, ENSRNOT00000098836.2

Conserved Domains (1) summary

COG1025
Location:23 → 927

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
XM_063282177.1 → XP_063138247.1 insulin-degrading enzyme isoform X5

UniProtKB/TrEMBL

A0A0G2K7Q7
XM_039102124.2 → XP_038958052.1 insulin-degrading enzyme isoform X6

UniProtKB/TrEMBL

A0A0G2K7Q7, A0A8I6A841

Related

ENSRNOP00000089992.1, ENSRNOT00000110995.2

Conserved Domains (1) summary

COG1025
Location:23 → 927

Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
XM_063282174.1 → XP_063138244.1 insulin-degrading enzyme isoform X4

UniProtKB/TrEMBL

A0A0G2K7Q7