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IDE insulin degrading enzyme [ Homo sapiens (human) ]

Gene ID: 3416, updated on 11-Apr-2024

Summary

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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

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See IDE in Genome Data Viewer
Location:
10q23.33
Exon count:
32
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (92451684..92574093, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (93330970..93453429, complement)
105.20220307 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 uncharacterized LOC124902484 Neighboring gene MARK2 pseudogene 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2617 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3771 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3772 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3774 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:94352873-94353624 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:94357207-94357722 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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins. Yilmaz A, et al. Biomolecules, 2023 May 26. PMID 37371470, Free PMC Article
  2. Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid β Oligomers by Insulin Degrading Enzyme. Abramov-Harpaz K, et al. Biomolecules, 2022 Dec 16. PMID 36551314, Free PMC Article
  3. Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease. Šerý O, et al. Curr Alzheimer Res, 2022. PMID 35236268
  4. Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations. Ghoula M, et al. Int J Mol Sci, 2022 Feb 3. PMID 35163673, Free PMC Article
  5. Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits. Borges DO, et al. Metabolism, 2021 May. PMID 33631143

See all (229) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.
    Title: Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
EBI GWAS Catalog
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ35968

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 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 ubiquitin-modified protein reader activity 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
  
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 
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
NP_001309722.1
NP_001309723.1
NP_001309724.1
NP_001309725.1
NP_001309726.1
NP_001397903.1
NP_004960.2
XP_016871676.1
XP_016871677.1
XP_016871679.2
XP_047281125.1
XP_047281127.1
XP_047281128.1
XP_047281129.1
XP_047281130.1
XP_047281131.1
XP_054221719.1
XP_054221720.1
XP_054221721.1
XP_054221722.1
XP_054221723.1
XP_054221724.1
XP_054221725.1
XP_054221726.1
XP_054221727.1

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_001165946.2 → 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)

  2. 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

  3. 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

  4. 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]

  5. 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]

  6. 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

  7. 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

  8. 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

  1. NR_136399.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL356128
    Related
    ENST00000678844.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    92451684..92574093 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047425171.1 → XP_047281127.1  insulin-degrading enzyme isoform X3

  2. XM_017016190.2 → XP_016871679.2  insulin-degrading enzyme isoform X2

  3. XM_047425169.1 → XP_047281125.1  insulin-degrading enzyme isoform X1

  4. 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]

  5. 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]

  6. XM_047425174.1 → XP_047281130.1  insulin-degrading enzyme isoform X6

    UniProtKB/TrEMBL
    A0A7I2V373
    Related
    ENSP00000503274.1, ENST00000677434.1

  7. XM_047425172.1 → XP_047281128.1  insulin-degrading enzyme isoform X4

  8. XM_047425175.1 → XP_047281131.1  insulin-degrading enzyme isoform X7

  9. XM_047425173.1 → XP_047281129.1  insulin-degrading enzyme isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    93330970..93453429 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054365746.1 → XP_054221721.1  insulin-degrading enzyme isoform X3

  2. XM_054365748.1 → XP_054221723.1  insulin-degrading enzyme isoform X1

  3. XM_054365744.1 → XP_054221719.1  insulin-degrading enzyme isoform X2

  4. XM_054365747.1 → XP_054221722.1  insulin-degrading enzyme isoform X3

  5. XM_054365745.1 → XP_054221720.1  insulin-degrading enzyme isoform X3

  6. XM_054365751.1 → XP_054221726.1  insulin-degrading enzyme isoform X6

    UniProtKB/TrEMBL
    A0A7I2V373

  7. XM_054365749.1 → XP_054221724.1  insulin-degrading enzyme isoform X4

  8. XM_054365752.1 → XP_054221727.1  insulin-degrading enzyme isoform X7

  9. XM_054365750.1 → XP_054221725.1  insulin-degrading enzyme isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P14735.4 GenPept UniProtKB/Swiss-Prot:P14735

Gene LinkOut

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