Tchem IDE Insulin-degrading enzyme

Protein Summary

Description

Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia. (Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV). 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]

Uniprot Accession IDs

• P14735
• B2R721
• B7ZAU2
• D3DR35
• Q5T5N2

Gene Name

• IDE

Ensembl ID

• ENST00000265986
• ENSP00000265986
• ENSG00000119912
• ENST00000371581
• ENSP00000360637

Symbol

• INSULYSIN

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
transcription factor perturbation	0.88
cellular component	0.86
kinase perturbation	0.84
biological term	0.83

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Metalloprotease / Insulin-degrading Enzyme

DTO Classes

Protein / Enzyme / Protease / Metalloprotease / Insulin-degrading Enzyme

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 505.25   (req: < 5)

Gene RIFs: 103   (req: <= 3)

Antibodies: 458   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 505.25   (req: >= 5)

Gene RIFs: 103   (req: > 3)

Antibodies: 458   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 38

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (38)

Explore Active Ligands

1 – 10 of 38

Ebselen

IDETchem Enzyme

pKi : 7.03

NTE-1

IDETchem Enzyme

pIC50 : 8.4

NTE-2

IDETchem Enzyme

pIC50 : 7.74

quinoline 2

IDETchem Enzyme

pIC50 : 5.7

CHEMBL2324206

IDETchem Enzyme

pKi : 6.39

CHEMBL2324220

IDETchem Enzyme

pKi : 7.42

CHEMBL4211248

IDETchem Enzyme

pKd : 7.66

CHEMBL2324207

IDETchem Enzyme

pKi : 6.61

CHEMBL2324201

IDETchem Enzyme

pKi : 6.56

CHEMBL2324204

IDETchem Enzyme

pKi : 6.64

Protein-Protein Interactions (183)

Explore Interacting Targets

1 – 10 of 183

• See Interactions on String-DB

LYPD6B

Tdark

Novelty:  0.1409054

p_int:  0.999774099

p_ni:  0.000225901

Data Source:  BioPlex

HOXC9

Tbio

Family:  TF

Novelty:  0.02524418

p_int:  0.997698709

p_ni:  0.002301291

Score:  0.534

Data Source:  BioPlex,STRINGDB

RPGR

Tbio

Family:  Enzyme

Novelty:  0.002733

p_int:  0.993263001

p_ni:  0.006736998

Score:  0.184

Data Source:  BioPlex,STRINGDB

SPINK2

Tdark

Family:  Enzyme

Novelty:  0.06832697

p_int:  0.989303591

p_ni:  0.010696409

Data Source:  BioPlex

PPP1R32

Tdark

Family:  Enzyme

Novelty:  0.38056479

p_int:  0.986172915

p_ni:  0.013827085

Score:  0.237

Data Source:  BioPlex,STRINGDB

FAM19A3

Tdark

Novelty:  0.37183557

p_int:  0.975295547

p_ni:  0.024704453

Data Source:  BioPlex

CTAGE5

Tbio

Novelty:  0.04516631

p_int:  0.969982198

p_ni:  0.030017802

Data Source:  BioPlex

TINAG

Tbio

Novelty:  0.04582927

p_int:  0.964482914

p_ni:  0.035517086

Data Source:  BioPlex

ARSG

Tbio

Family:  Enzyme

Novelty:  0.04412917

p_int:  0.94377418

p_ni:  0.05622582

Data Source:  BioPlex

CCL3L1

Tbio

Novelty:  0.01124082

p_int:  0.93965188

p_ni:  0.06034812

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (8)

Reactome (6)

KEGG (1)

WikiPathways (1)

Deubiquitination (R-HSA-5688426)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Peroxisomal protein import	63 targets	R-HSA-9033241
Reactome	Post-translational protein modification	1450 targets	R-HSA-597592
Reactome	Protein localization	165 targets	R-HSA-9609507

Name	Explore in Pharos	Explore in Source
Deubiquitination	278 targets	R-HSA-5688426
Metabolism of proteins	2050 targets	R-HSA-392499
Peroxisomal protein import	63 targets	R-HSA-9033241
Post-translational protein modification	1450 targets	R-HSA-597592
Protein localization	165 targets	R-HSA-9609507

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (43)

Functions (13)

Components (11)

Processes (19)

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1 – 10 of 13

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
insulin binding	Inferred from Direct Assay (IDA)	UniProtKB
metalloendopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
peptide binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
signaling receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin-dependent protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
amyloid-beta binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (15)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	2	2	2		87.7
eosinophil percentage of leukocytes	EFO_0007991	1	1	1		80.5
childhood onset asthma	EFO_0004591	1	1	0	1.1	72.6
asthma	EFO_0000270	3	3	0	1	71.8
red blood cell density measurement	EFO_0007978	1	1	1		53.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	2		87.7
eosinophil percentage of leukocytes	EFO_0007991	1		80.5
childhood onset asthma	EFO_0004591	0	1.1	72.6
asthma	EFO_0000270	0	1	71.8
red blood cell density measurement	EFO_0007978	1		53.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Allosteric enzyme
Alternative splicing
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Host cell receptor for virus entry
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
asthma
basophil percentage of leukocytes
childhood onset asthma
eosinophil count
eosinophil percentage of leukocytes
HbA1c measurement
Inhalant adrenergic use measurement
intraocular pressure measurement
mean platelet volume
red blood cell density measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cardiovascular system phenotype
craniofacial phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
nervous system phenotype
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	insulin degrading enzyme	VGNC:7230	450608
Macaque	insulin degrading enzyme		698640
Mouse	insulin degrading enzyme	MGI:96412	15925
Rat	insulin degrading enzyme	RGD:2861	25700
Dog	insulin degrading enzyme	VGNC:41863	477768

Species	Name	OMA	EggNOG	Inparanoid
Chimp	insulin degrading enzyme
Macaque	insulin degrading enzyme
Mouse	insulin degrading enzyme
Rat	insulin degrading enzyme
Dog	insulin degrading enzyme

Publication Statistics

PubMed Score 505.25

PubMed score by year

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PubTator Score 509.01

PubTator score by year

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Related Publications

Text Mined References (169)

GeneRif Annotations (103)

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PMID	Year	Title