IDE - insulin degrading enzyme Gene

Also Known as INSULYSIN

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 3416

About IDE

Cytogenetic location: 10q23.33 Genomic coordinates (GRCh38): 10:92,451,684-92,574,093 (from NCBI)

This gene has 38 transcripts (splice variants), 225 orthologues and 6 paralogues. Ubiquitous expression in skin (RPKM 17.4), testis (RPKM 9.9) and 25 other tissues.

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]

IDE Products (8)

mRNA	Protein	Name
NM_001165946.2	NP_001159418.1	insulin-degrading enzyme isoform 2
NM_001322793.2	NP_001309722.1	insulin-degrading enzyme isoform 3
NM_001322794.2	NP_001309723.1	insulin-degrading enzyme isoform 4
NM_001322795.2	NP_001309724.1	insulin-degrading enzyme isoform 5
NM_001322796.1	NP_001309725.1	insulin-degrading enzyme isoform 5
NM_001322797.2	NP_001309726.1	insulin-degrading enzyme isoform 6
NM_001410974.1	NP_001397903.1	insulin-degrading enzyme isoform 7
NM_004969.4	NP_004960.2	insulin-degrading enzyme isoform 1

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	Referencias	Source
enables ATP binding	IDA IDA: Inferred from direct assay	17613531	GOA
enables endopeptidase activity	IDA IDA: Inferred from direct assay	20364150	GOA
enables identical protein binding	IPI IPI: Inferred from physical interaction	17051221	GOA
enables insulin binding	IDA IDA: Inferred from direct assay	17051221	GOA
enables insulin binding	IPI IPI: Inferred from physical interaction	20082125	GOA
enables metalloendopeptidase activity	IDA IDA: Inferred from direct assay	17051221	GOA
enables peptide binding	IPI IPI: Inferred from physical interaction	20082125	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	17051221	GOA
enables protein homodimerization activity	IDA IDA: Inferred from direct assay	17613531	GOA
enables zinc ion binding	IDA IDA: Inferred from direct assay	17613531	GOA

Biological Process GO Annotation	Evidence	Referencias	Source
involved in amyloid-beta clearance	IMP IMP: Inferred from mutant phenotype	10684867	GOA
involved in amyloid-beta clearance by cellular catabolic process	IMP IMP: Inferred from mutant phenotype	23525105	GOA
involved in amyloid-beta metabolic process	IDA IDA: Inferred from direct assay	9830016	GOA
involved in antigen processing and presentation of endogenous peptide antigen via MHC class I	IMP IMP: Inferred from mutant phenotype	20364150	GOA
involved in bradykinin catabolic process	IDA IDA: Inferred from direct assay	17613531	GOA
involved in hormone catabolic process	IDA IDA: Inferred from direct assay	19321446	GOA
involved in insulin catabolic process	IDA IDA: Inferred from direct assay	9231799	GOA
involved in insulin metabolic process	IDA IDA: Inferred from direct assay	18448515	GOA
involved in peptide catabolic process	IDA IDA: Inferred from direct assay	20364150	GOA
involved in positive regulation of protein binding	IDA IDA: Inferred from direct assay	9830016	GOA
involved in protein catabolic process	IMP IMP: Inferred from mutant phenotype	20364150	GOA
involved in proteolysis	IDA IDA: Inferred from direct assay	18602473	GOA
involved in proteolysis involved in protein catabolic process	IDA IDA: Inferred from direct assay	9830016	GOA
involved in regulation of aerobic respiration	IGI IGI: Inferred from genetic interaction	23525105	GOA
involved in ubiquitin recycling	IDA IDA: Inferred from direct assay	21185309	GOA

Cellular Component GO Annotation	Evidence	Referencias	Source
located in basolateral plasma membrane	IMP IMP: Inferred from mutant phenotype	16511862	GOA
located in cell surface	IDA IDA: Inferred from direct assay	16511862	GOA
located in cytoplasm	IDA IDA: Inferred from direct assay	9231799	GOA
located in cytosol	IDA IDA: Inferred from direct assay	9830016	GOA
located in external side of plasma membrane	IDA IDA: Inferred from direct assay	16511862	GOA
located in extracellular space	IDA IDA: Inferred from direct assay	9830016	GOA
located in mitochondrion	IDA IDA: Inferred from direct assay	15285718	GOA
NOT located in nucleus	IDA IDA: Inferred from direct assay	18226493	GOA
located in nucleus	IDA IDA: Inferred from direct assay	9231799	GOA
located in peroxisome	IDA IDA: Inferred from direct assay	9231799	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

IDE Protein Structure

Peptidase_M16

Peptidase_M16_C

0
200
400
600
800
1019 a.a.

Protein Preferred Names	Protein Names
insulin-degrading enzyme	Abeta-degrading protease

IDE Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	Referencias
Intra	IDE	P14735	CCL3	Homo sapiens	P10147	X-Ray Diffraction	20959807
Intra	IDE	P14735	CCL3	Homo sapiens	P10147	Protease Assay	20959807

Cross: Cross-species interaction Intra: Intraspecies interaction

Recombinant IDE Proteins

Referencia número	Nombre del producto	Accession	Pureza
HY-P70291	Insulysin/IDE Protein, Human (HEK293, His)	P14735-1 (M42-L1019)	≥ 95%, as determined by reducing SDS-PAGE.

IDE Antibodies

Referencia número	Nombre del producto	Aplicación	Reactivity
HY-P80191	Insulin degrading enzyme Antibody (YA342)	WB, IHC-P, IHC-F, IF-Tissue	Human, Mouse, Rat
HY-P85666	Insulin degrading enzyme Antibody (YA5358)	WB, IHC-P, ICC/IF,	Human, Hamster

Related Diseases

Diseases	Alias
Glucose Intolerance	Glucose: Intolerance Glucose: Malabsorption Malabsorption Of Glucose Impaired Glucose Tolerance
Type 2 Diabetes Mellitus	Insulin Resistance NIDDM Type 2 Diabetes Diabetes Mellitus, Non-Insulin-Dependent T2D Noninsulin-Dependent Diabetes Mellitus Diabetes Mellitus, Type Ii Maturity-Onset Diabetes Insulin Resistance, Severe, Digenic Diabetes Mellitus, Type 2 Diabetes Mellitus, Noninsulin-Dependent Diabetes Mellitus, Noninsulin-Dependent, Association With Diabetes Mellitus, Noninsulin-Dependent, Late Onset Hypertension, Insulin Resistance-Related, Susceptibility To Insulin Resistance, Susceptibility To Non-Insulin-Dependent Diabetes Mellitus Type Ii Diabetes Mellitus Adult-Onset Diabetes Mellitus Maturity-Onset Diabetes Mellitus Diabetes Mellitus Type 2 Type Ii Diabetes Type 2 Diabetes Mellitus, Susceptibility To Diabetes, Type 2 Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To Diabetes Mellitus, Type 2, Susceptibility To Diabetes Mellitus, Noninsulin-Dependent, 2 Diabetes Mellitus, Type Ii, Susceptibility To Hypertension, Insulin Resistance-Related Adult-Onset Diabetes Aodm Diabetes Mellitus, Adult-Onset Diabetes Mellitus Type Ii Diabetes Mellitus Type 2, Susceptibility To Diabetes, Type Ii, Susceptibility To Diabetes Type 2 Diabetes Mellitus Adult Onset Diabetes Maturity Onset Diabetes Nonketotic Diabetes Non-Insulin Dependent Diabetes Mellitus T2dm - [Type 2 Diabetes Mellitus] Niddm - [Non Insulin Dependent Diabetes Mellitus] Dm2 Dm Type Ii Diabetic Type 2 Insulin Requiring Type 2 Diabetes Noninsulin Dependent Diabetes Non-Insulin-Dependent Diabetes Mellitus Without Complications Diabetes Due To Insulin Secretory Defect Diabetes Mellitus Due To Insulin Secretory Defect Non-Insulin-Dependent Diabetes Of The Young Senile Diabetes Nonketotic Hyperglycaemia Stable Diabetes
Alzheimer Disease, Familial, 1	Alzheimer Disease Alzheimer'S Disease Presenile And Senile Dementia AD1 Alzheimer Disease, Susceptibility To Alzheimer Disease, Late-Onset, Susceptibility To Alzheimer Disease 1, Familial AD Familial Alzheimer Disease Alzheimer Disease, Late-Onset Alzheimers Dementia Alzheimer Dementia Alzheimer Sclerosis Alzheimer Syndrome Alzheimer-Type Dementia Dat Primary Senile Degenerative Dementia Sdat Alzheimer Disease 1 Autosomal Dominant Alzheimer Disease Early-Onset Alzheimer Disease With Cerebral Amyloid Angiopathy Late Onset Alzheimer Disease Alzheimers Disease Alzheimer Disease, Early-Onset, With Cerebral Amyloid Angiopathy Late-Onset Alzheimers Disease Alzheimer'S Disease Pathway Kegg Dementia Due To Alzheimer'S Disease Alzheimer Disease Type 1 Alzheimers
Alzheimer Disease 6	Ad6 Alzheimer Disease 6, Late-Onset Alzheimer'S Disease 6 Alzheimer Disease 6, Late Onset
Diabetes Mellitus	Diabetes
Amyloidosis	Amyloid Disease Amyloid Amyloid Degeneration Amyloidosis Nos Amyloid Deposition Amyloid Infiltration Idiopathic Amyloidosis Hyaloid Degeneration Lardaceous Degeneration
Cerebral Amyloid Angiopathy, Cst3-Related	Cerebral Amyloid Angiopathy Hereditary Cerebral Hemorrhage With Amyloidosis Hchwa Hereditary Cystatin C Amyloid Angiopathy Cerebral Amyloid Angiopathy, Familial Amyloidosis, Cerebroarterial, Icelandic Type Amyloidosis Vi Cerebral Hemorrhage, Hereditary, With Amyloidosis Cst3-Related Cerebral Amyloid Angiopathy Cerebral Hemorrhage, Hereditary, With Amyloidosis, Icelandic Variant Hereditary Cerebral Hemorrhage With Amyloidosis, Icelandic Variant Caa, Familial Cerebral Amyloid Angiopathy, Genetic Acys Amyloidosis Cst3-Related Amyloidosis Cystatin Amyloidosis Hchwa, Icelandic Type Hereditary Cerebral Hemorrhage With Amyloidosis, Icelandic Type Amyloidosis 6 AMYL6 Acys Caa Cerebral Amyloid Angiopathy Cst3-Related Cerebroarterial Amyloidosis Icelandic Type Cystatin C Amyloidosis Hccaa Hchwai Hchwa-I Hereditary Cerebral Hemorrhage With Amyloidosis Icelandic Type Cerebral Amyloid Angiopathy Familial Angiopathy, Amyloid, Cerebral, Cst3-Related Hereditary Cerebral Amyloid Angiopathy, Icelandic Type Familial Cerebral Amyloid Angiopathy Cerebral Amyloid Angiopathy, Hereditary
Dementia	Dementias Presenile Dementia Alzheimer Type Dementia Alzheimer Sclerosis Alzheimer Disease Dementia Alzheimer Dementia Primary Degenerative Alzheimer Type Dementia End Stage Alzheimer'S Dementia Alzheimer'S Type Atypical Dementia Alzheimer Type Presenile Dementia Early Onset Alzheimer Dementia Dementia In Alzheimer Disease Type 2 Dementia In Alzheimer Disease With Early Onset Early Onset Alzheimer Type Dementia, Uncomplicated Primary Degenerative Alzheimer Type Dementia, Early Onset Primary Degenerative Alzheimer Type Dementia, Presenile Onset, Uncomplicated Alzheimer Disease Dementia With Early Onset Presenile Sclerosis Presenile Brain Sclerosis Presenile Alzheimer Brain Sclerosis Late Onset Alzheimer Dementia Dementia In Alzheimer Disease Type 1 Dementia In Alzheimer Disease With Late Onset Primary Degenerative Alzheimer Type Dementia, Late Onset Sdat - [Senile Dementia, Alzheimer Type] Alzheimer Disease Dementia With Late Onset Late Onset Alzheimer Brain Sclerosis Senile Alzheimer Brain Disease Senile Alzheimer Brain Sclerosis Senile Primary Degenerative Alzheimer Type Dementia Senile Dementia Of The Alzheimer Type Arteriosclerotic Dementia Strategic-Infarct Dementia Post Stroke Dementia Vascular Cognitive Impairment Vascular Dementia Dementia Of The Lewy Body Type Dementia With Lewy Bodies Sdlt - [Senile Dementia Of The Lewy Body Type] Senile Dementia Of The Lewy Body Type Alcohol-Related Dementia Alcoholic Dementia Nos Alcohol-Induced Dementia Alcoholic Brain Syndrome Chronic Alcoholic Brain Syndrome Alcohol Dementia Late Onset Alcoholic Psychosis Residual And Late-Onset Alcohol-Induced Psychotic Disorder Mental And Behavioural Disorders Due To Use Of Sedatives Or Hypnotics, Residual And Late-Onset Psychotic Disorder Late-Onset Psychoactive Substance-Induced Psychotic Disorder Inhalant Dementia Volatile Solvents Dementia Dementia In Paralysis Agitans Pdd - [Parkinson Disease Dementia] Dementia Syndrome Of Parkinson Disease Dementia In Parkinson Disease Parkinson Related Dementia Dementia In Huntington Chorea Hiv - [Human Immunodeficiency Virus] Dementia Hiv- [Human Immunodeficiency Virus] Associated Cognitive Motor Complex Hiv- [Human Immunodeficiency Virus] Associated Dementia Complex Aids - [Acquired Immunodeficiency Syndrome] Dementia Complex Aids Related Dementia Dementia Due To Niacin Deficiency
Familial Atrial Fibrillation	Atrial Fibrillation, Familial Atfb Atrial Fibrillation Autosomal Dominant Autosomal Dominant Atrial Fibrillation Auricular Fibrillation Atrial Fibrillation Atrial Fibrillation, Familial, 1
Hyperinsulinism	Hyperinsulinemia
Cerebral Amyloid Angiopathy, App-Related	Hchwad Amyloidosis, Cerebroarterial, App-Related Amyloidosis, Hereditary, With Cerebral Hemorrhage, Dutch Variant Cerebral Amyloid Angiopathy, App-Related, Dutch Variant Cerebral Amyloid Angiopathy, App-Related, Iowa Variant Cerebral Amyloid Angiopathy, App-Related, Italian Variant Cerebral Amyloid Angiopathy, App-Related, Flemish Variant Cerebral Amyloid Angiopathy, App-Related, Arctic Variant Cerebral Amyloid Angiopathy, Dutch, Italian, Iowa, Flemish, Arctic Variants App-Related Cerebral Amyloid Angiopathy Abetaa21g Amyloidosis Abeta Amyloidosis, Italian Type Abeta Amyloidosis, Arctic Type Abeta Amyloidosis, Iowa Type Abeta Amyloidosis, Dutch Type Hchwa-D Abeta Amyloidosis, Flemish Type Abetaa21g-Related Amyloidosis Hchwa, Flemish Type Hereditary Cerebral Hemorrhage With Amyloidosis, Flemish Type Abetae22k Amyloidosis Hchwa, Italian Type Hereditary Cerebral Hemorrhage With Amyloidosis, Italian Type Abetae22g Amyloidosis Hchwa, Arctic Type Hereditary Cerebral Hemorrhage With Amyloidosis, Arctic Type Abetad23n Amyloidosis Hchwa, Iowa Type Hereditary Cerebral Hemorrhage With Amyloidosis, Iowa Type Abetal34v Amyloidosis Abeta Amyloidosis, Piedmont Type Abetal34v-Related Amyloidosis Hchwa, Piedmont Type Hereditary Cerebral Hemorrhage With Amyloidosis, Piedmont Type Abetae22q Amyloidosis Hchwa, Dutch Type Hereditary Cerebral Hemorrhage With Amyloidosis, Dutch Type CAA-APP Amyloidosis Cerebroarterial App-Related Amyloidosis Hereditary With Cerebral Hemorrhage Dutch Variant Cerebral Amyloid Angiopathy App-Related Arctic Variant Cerebral Amyloid Angiopathy App-Related Dutch Variant Cerebral Amyloid Angiopathy App-Related Flemish Variant Cerebral Amyloid Angiopathy App-Related Iowa Variant Cerebral Amyloid Angiopathy App-Related Italian Variant Familial Occipital Calcifications With Hemorrhagic Strokes Leukoencephalopathy Arterial Dysplasia Dementia Fochs-Ladd Hereditary Cerebral Amyloid Angiopathy Dutch Type Hereditary Cerebral Hemorrhage With Amyloidosis Dutch Type Hereditary Cerebral Hemorrhage With Amyloidosis Italian Type Cerebral Hemorrhage With Amyloidosis, Hereditary, Dutch Type
Mild Cognitive Impairment
Vascular Dementia	Dementia, Vascular Multi Infarct Dementia Multifocal Dementia Dementia Vascular Vascular Dementia, Susceptibility To Dementia, Multi-Infarct Multi-Infarct Dementia
Nervous System Disease	Abnormality Of The Nervous System Nervous System Diseases Nervous System Disorder

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Clinical Phase
Pre-clinical Phase

Clinical Phase

Bioactive Molecules (2)

Referencia número	Nombre del producto	Efecto	Pureza	Phase
HY-101569	Darovasertib	Inhibitor	99.78%	Phase 3
HY-169422	GSK4418959	Inhibitor	99.07%	Phase 2

Pre-clinical Phase

Bioactive Molecules (17)

Referencia número	Nombre del producto	Efecto	Pureza	Rare Diseases
HY-N7135	Tropolone	Inhibitor	99.98%	Unkown
HY-100533	IDE1		99.13%	Unkown
HY-110197	6bK TFA	Inhibitor	99.68%	Unkown
HY-100534	IDE 2	Agonist	99.00%	Unkown
HY-117878	ML345	Inhibitor	99.37%	Unkown
HY-W157689	IDE-IN-2	Inhibitor	98.04%	Unkown
HY-169422A	GSK4418959 (enantiomer)		95.0%	Unkown
HY-W038421	1,3-Bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene		≥98.0%	Unkown
HY-110197A	6bK formate	Inhibitor	97.02%	Unkown
HY-114611	BDM44768		/	Unkown
HY-12655	IDE-IN-1	Inhibitor	/	Unkown
HY-143401	Hit 1	Activator	/	Unkown
HY-182280	BDM71230		/	Unkown
HY-RS06526	IDE Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-W616806	Sodium 6-oxo-3,6-dihydropurin-7-ide		/	Unkown
HY-RS16920	Ide Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS23363	Ide Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Inhibitory Antibodies (1)

Referencia número	Nombre del producto	Efecto	Pureza	Rare Diseases
HY-P992056	Anti-Human/Mouse LY6E Antibody (9B12)		/	Unkown