Tchem IDE Insulin-degrading enzyme

Protein Classes

PANTHER Classes

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

DTO Classes

Protein / Enzyme / Protease / Metalloprotease / 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

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: 422.08   (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: 422.08   (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: 31

Tclin

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

Active Drug: 0

Active Ligands (31)

Explore Active Ligands

1 – 10 of 31

CHEMBL2324201

IDETchem Enzyme

Ki: 7.59

CHEMBL2324207

IDETchem Enzyme

Ki: 7.64

CHEMBL2324206

IDETchem Enzyme

Ki: 8.85

CHEMBL2324220

IDETchem Enzyme

Ki: 8.53

CHEMBL2324205

IDETchem Enzyme

Ki: 7.07

CHEMBL2324204

IDETchem Enzyme

Ki: 7.3

CHEMBL2324203

IDETchem Enzyme

Ki: 7.06

CHEMBL3235416

IDETchem Enzyme

IC50: 7

CHEMBL2324202

IDETchem Enzyme

Ki: 6.99

CHEMBL2324213

IDETchem Enzyme

Ki: 6.3

Protein Data Bank (50)

1 – 5 of 50

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (8)

Reactome (6)

KEGG (1)

WikiPathways (1)

Deubiquitination (R-HSA-5688426)

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Items per page:

5

1 – 5 of 6

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

Gene Ontology Terms (43)

Functions (13)

Components (11)

Processes (19)

Items per page:

10

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

Protein-Protein Interactions (183)

Explore Interacting Targets

1 – 10 of 183

• See Interactions on String-DB

LYPD6B

Tdark

Novelty: 0.28952206

p_int: 0.999774099

p_ni: 0.000225901

Data Source: BioPlex

HOXC9

Tbio

Family: TF

Novelty: 0.03402121

p_int: 0.997698709

p_ni: 0.002301291

Score: 0.534

Data Source: BioPlex,STRINGDB

RPGR

Tbio

Family: Enzyme

Novelty: 0.00353224

p_int: 0.993263001

p_ni: 0.006736998

Score: 0.184

Data Source: BioPlex,STRINGDB

SPINK2

Tdark

Family: Enzyme

Novelty: 0.0882707

p_int: 0.989303591

p_ni: 0.010696409

Data Source: BioPlex

PPP1R32

Tdark

Family: Enzyme

Novelty: 0.4

p_int: 0.986172915

p_ni: 0.013827085

Score: 0.237

Data Source: BioPlex,STRINGDB

FAM19A3

Tdark

Novelty: 0.43478261

p_int: 0.975295547

p_ni: 0.024704453

Data Source: BioPlex

CTAGE5

Tbio

Novelty: 0.06289332

p_int: 0.969982198

p_ni: 0.030017802

Data Source: BioPlex

TINAG

Tbio

Novelty: 0.04045398

p_int: 0.964482914

p_ni: 0.035517086

Data Source: BioPlex

ARSG

Tbio

Family: Enzyme

Novelty: 0.0408666

p_int: 0.94377418

p_ni: 0.05622582

Data Source: BioPlex

CCL3L1

Tbio

Novelty: 0.01605247

p_int: 0.93965188

p_ni: 0.06034812

Data Source: BioPlex

Publication Statistics

PubMed Score  422.08

PubMed score by year

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PubTator Score  509.01

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPEDKREYRGLELA

1-70

NGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNA

70-140

FTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDESCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGN

140-210

PKHPFSKFGTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVCVLGRESLDDLTNLVVKLFSEVEN

210-280

KNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSEL

280-350

KSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAV

350-420

AFRFKDKERPRGYTSKIAGILHYYPLEEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTD

420-490

RTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFEILPLEKEATPYPALIKDTAMSKLW

490-560

FKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLS

560-630

VKGYNDKQPILLKKIIEKMATFEIDEKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDEL

630-700

KEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGIMQMVEDTLIEHAHTKPLLPSQLVRYREVQ

700-770

LPDRGWFVYQQRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRA

770-840

NGIQGLRFIIQSEKPPHYLESRVEAFLITMEKSIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGE

840-910

IISQQYNFDRDNTEVAYLKTLTKEDIIKFYKEMLAVDAPRRHKVSVHVLAREMDSCPVVGEFPCQNDINL

910-980

SQAPALPQPEVIQNMTEFKRGLPLFPLVKPHINFMAAKL

980-1019

MRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDESCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVCVLGRESLDDLTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGILHYYPLEEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFEILPLEKEATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKGYNDKQPILLKKIIEKMATFEIDEKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGIMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQQRNEVHNNCGIEIYYQTDMQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITMEKSIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGEIISQQYNFDRDNTEVAYLKTLTKEDIIKFYKEMLAVDAPRRHKVSVHVLAREMDSCPVVGEFPCQNDINLSQAPALPQPEVIQNMTEFKRGLPLFPLVKPHINFMAAKL

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Uniprot Keyword

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