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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

IDE Gene

protein-coding GIFtS: 69
GCID: GC10M094201

insulin-degrading enzyme

Explore 37 diseases affiliated with
IDE via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Insulin-Degrading Enzyme¹ ²		Insulinase³
Insulin Protease² ³		Insulinase³
Abeta-Degrading Protease² ³		Insulysin³
EC 3.4.24.56³ ⁸		EC 3.4.24⁸
INSULYSIN²

External Ids:	HGNC: 5381¹	Entrez Gene: 3416²	Ensembl: ENSG00000119912⁷	OMIM: 146680⁵	UniProtKB: P14735³

Export aliases for IDE gene to outside databases

Previous GC identifers: GC10M093095 GC10M093435 GC10M094342 GC10M093878 GC10M087837

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for IDE:

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)

UniProtKB/Swiss-Prot: IDE_HUMAN, P14735

Function: 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

Gene Wiki entry for IDE (Insulin-degrading enzyme)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000010.10 NC_018921.1 NT_030059.13

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the IDE gene promoter:
E2F-4 E2F-5 NF-YC CBF-C CBF-A CBF-B CP1A CP1C NF-Y CBF(2)
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: IDE promoter sequence

Search SABiosciences Chromatin IP Primers for IDE

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat IDE

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q23-q25 Ensembl cytogenetic band: 10q23.33 HGNC cytogenetic band: 10q23-q25

IDE Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
IDE gene location

GeneLoc information about chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10M094201: view genomic region (about GC identifiers)

Start:	94,211,441 bp from pter	End:	94,333,852 bp from pter
Size:	122,412 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: IDE_HUMAN, P14735 (See protein sequence)

Recommended Name: Insulin-degrading enzyme

Size: 1019 amino acids; 117968 Da

Cofactor: Binds 1 zinc ion per subunit

Subunit: Homodimer. Can form higher oligomers. Interacts (via N-terminus) with varicella-zoster virus (VZV) envelope

glycoprotein E (via N-terminus); the membrane-associated isoform may function as an entry receptor for this virus

Subcellular location: Cytoplasm. Cell membrane. Secreted (By similarity). Note=Present at the cell surface of neuron

cells. The membrane-associated isoform is approximately 5 kDa larger than the known cytosolic isoform

Miscellaneous: ATP-binding induces a conformation change

6/21 PDB 3D structures from and Proteopedia for IDE (see all 21):

2G47 (3D)

2G48 (3D)

2G49 (3D)

2G54 (3D)

2G56 (3D)

2JBU (3D)

Secondary accessions: B2R721 B7ZAU2 D3DR35 Q5T5N2

Alternative splicing: 2 isoforms: P14735-1 P14735-2

Explore the universe of human proteins at neXtProt for IDE: NX_P14735

Post-translational modifications:

The N-terminus is blocked¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P14735

4/7 DME Specific Peptides for IDE (P14735) (see all 7)

YYSSNLM

EHMLFLGT

KVLLISDP

KIVPIKDIR

IDE Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001159418.1 NP_004960.2

ENSEMBL proteins:

ENSP00000265986 ENSP00000408850 ENSP00000360637

Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for IDE (Insulysin/IDE)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: IDE OriGene Protein Over-expression Lysate: IDE OriGene Custom Protein Services for IDE
	GenScript Custom Purified and Recombinant Proteins Services for IDE
	Novus Biologicals IDE Proteins Novus Biologicals IDE Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for IDE

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005615	extracellular space	IDA	9830016
GO:0005634	NOT nucleus	IDA	18226493
GO:0005737	cytoplasm	IDA	9830016
GO:0005739	mitochondrion	IDA	15285718
GO:0005777	peroxisome	IDA	9231799

IDE for ontologies About GeneDecksing

IDE Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of IDE
	R&D Systems Antibodies for IDE (Insulysin/IDE)
	OriGene Antibodies (see all 3): IDE OriGene Custom Antibody Services for IDE
	GenScript Superior Antibodies for IDE
	Novus Biologicals IDE Antibodies
	Abcam antibodies for IDE
	Uscn Antibodies for IDE
	ThermoFisher Antibodies for IDE

Assay Products for IDE:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript IDE-Activity-based Protease Assay for Compound Screening
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for IDE

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

IDE for domains About GeneDecksing

5 InterPro domains/families:

IPR001431 Pept_M16_Zn_BS

IPR011765 Pept_M16_N

IPR011237 Pept_M16_dom

IPR007863 Peptidase_M16_C

IPR011249 Metalloenz_LuxS/M16

Graphical View of Domain Structure for InterPro Entry P14735

ProtoNet protein and cluster: P14735

1 Blocks protein family: IPB001431 Insulinase-like peptidase

UniProtKB/Swiss-Prot: IDE_HUMAN, P14735

Domain: The SlyX motif may be involved in the non-conventional secretion of the protein (By similarity)

Similarity: Belongs to the peptidase M16 family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: IDE_HUMAN, P14735

Function: 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

Catalytic activity: Degradation of insulin, glucagon and other polypeptides. No action on proteins

Enzyme regulation: Activated by small peptides (By similarity). Activated by ATP and GTP, and to a lesser extent by

CTP, TTP and PPPi. Inhibited by bacitracin. Inhibited by S-nitrosylation and oxidation agents

Genatlas biochemistry entry for IDE:

insulin degrading enzyme,cytosolic metalloproteinase (110kDa)

Enzyme Numbers (IUBMB): EC 3.4.24.56¹ ² EC 3.4.24²

miRNA Products:		OriGene 3'-UTR Clone (see all 2): IDE Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat IDE
		8/59 QIAGEN miScript miRNA Assays for microRNAs that regulate IDE (see all 59):
		hsa-miR-576-3p hsa-miR-193a-3p hsa-miR-29a hsa-miR-200a hsa-miR-30d hsa-miR-141 hsa-miR-30a hsa-miR-1184

		SwitchGear 3'UTR luciferase reporter plasmid: IDE 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IDE (see all 7) OriGene shRNA RFP: IDE OriGene siRNA: IDE
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IDE

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for IDE

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IDE (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for IDE (see all 2) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: IDE (NM_001279)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for IDE
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IDE

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for IDE
		Search LifeMap BioReagents cell lines for IDE

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IDE

Gene Ontology (GO): 5/15 molecular function terms (GO ID links to tree view) (see all 15): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001540	beta-amyloid binding	IEA	--
GO:0001948	glycoprotein binding	IPI	17055432
GO:0004222	metalloendopeptidase activity	IDA	17051221
GO:0005102	receptor binding	IPI	--
GO:0005515	protein binding	IPI	17715127

IDE for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for IDE:

Increased resistance to Trastu

Animal Models:
7 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Ide):

behavior/neurological	hematopoietic system	homeostasis/metabolism	immune system	nervous system
other	renal/urinary system

IDE for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Alzheimer's disease

0.43

Alzheimers Disease

0.00

A-beta Uptake & Degradation

A-beta Uptake & Degradation

1.00

Apoptotic Pathways in Synovial Fibroblasts

DHA Signaling

0.70

Pathway sources
See GeneCards unified pathways
Show all pathways

1 R&D Systems Pathway for IDE

A-beta Uptake & Degradation

1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for IDE

DHA Signaling

1 BioSystems Pathway for IDE

Alzheimers Disease

1 Kegg Pathway (Kegg details for IDE):

Alzheimer's disease

IDE for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for IDE

STRING Interaction Network Preview (showing 5 interactants - click image to see 21)

5/38 Interacting proteins for IDE (P14735^{2, 3} ENSP00000265986⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 38)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CCL3	P10147²^,³, ENSP00000225245⁴	MINT-8087623 MINT-8087747 MINT-8087595 I2D: score=1 STRING: ENSP00000225245
CCL4	P13236²^,³, ENSP00000250151⁴	MINT-8087616 I2D: score=1 STRING: ENSP00000250151
IGF1	P05019³, ENSP00000302665⁴	I2D: score=3 STRING: ENSP00000302665
APP	P05067³, ENSP00000284981⁴	I2D: score=2 STRING: ENSP00000284981
IGF2	P01344³, ENSP00000338297⁴	I2D: score=2 STRING: ENSP00000338297

About this table

Gene Ontology (GO): 5/19 biological process terms (GO ID links to tree view) (see all 19): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006200	ATP catabolic process	--	--
GO:0006508	proteolysis	IDA	--
GO:0008286	insulin receptor signaling pathway	NAS	3059494
GO:0008340	determination of adult lifespan	IDA	18448515
GO:0010815	bradykinin catabolic process	IDA	--

IDE for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

IDE for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for IDE

1 HMDB Compound for IDE About this table

Compound	Synonyms	CAS #	PubMed Ids
Zinc	Zinc (see all 2)	7440-66-6	--

3 DrugBank Compounds for IDE About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Insulin, porcine	--	9004-14-2	target	--	13560210 17016423 17139284 8504733 9643444
Bacitracin	--	1405-87-4	target	inhibitor	8484964 11752352
Insulin recombinant	--	9004-10-8	target	--	17139284 17016423

10/25 Novoseek chemical compound relationships for IDE gene (see all 25) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
thermolysin	59.2	4	7738784 (2), 8104941 (1), 7806544 (1)
chymostatin	53.7	2	7494830 (1), 7596985 (1)
1,10-phenanthroline	48.2	5	7789307 (1), 7494830 (1), 8024692 (1), 7738784 (1) (see all 5)
zinc	46.7	25	7806544 (4), 18621727 (2), 8104941 (1), 9128138 (1) (see all 13)
thimet	46.5	3	11809755 (1)
n-ethylmaleimide	46.3	5	7494830 (1), 8300632 (1), 7596985 (1), 18986166 (1)
triphosphate	40.3	5	15749695 (2), 15494400 (1), 16723115 (1)
p-chloromercuribenzoate	40.2	1	7494830 (1)
leupeptin	37.1	2	7494830 (1), 7596985 (1)
diisopropylfluorophosphate	28.1	1	7494830 (1)

Search CenterWatch for drugs/clinical trials and news about IDE

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for IDE gene (2 alternative transcripts):

NM_001165946.1 NM_004969.3

Unigene Cluster for IDE:

Insulin-degrading enzyme

Hs.500546 [show with all ESTs]

Unigene Representative Sequence: NM_004969

8 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000265986(uc001kia.3) ENST00000496903 ENST00000478361 ENST00000463640

ENST00000462988 ENST00000492362 ENST00000436178 ENST00000371581(uc010qnp.2 uc001khz.3)

miRNA Products:		OriGene 3'-UTR Clone (see all 2): IDE Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat IDE
		8/59 QIAGEN miScript miRNA Assays for microRNAs that regulate IDE (see all 59):
		hsa-miR-576-3p hsa-miR-193a-3p hsa-miR-29a hsa-miR-200a hsa-miR-30d hsa-miR-141 hsa-miR-30a hsa-miR-1184

		SwitchGear 3'UTR luciferase reporter plasmid: IDE 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IDE (see all 7) OriGene shRNA RFP: IDE OriGene siRNA: IDE
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IDE

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IDE (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for IDE (see all 2) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: IDE (NM_001279)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for IDE
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IDE

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for IDE Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat IDE
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat IDE
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat IDE

Additional cDNA sequence:

AB209204.1 AK093287.1 AK302578.1 AK312810.1 AK316407.1 BC036188.1 BC096336.1 BC096337.1

BC096338.1 BC096339.3 BX648462.1 M21188.1

10 DOTS entries:

DT.101980937 DT.99964461 DT.454997 DT.92434686 DT.121290466 DT.121290448 DT.101980938 DT.121290477

DT.313438 DT.95278073

24/208 AceView cDNA sequences (see all 208):

CB854795 CK824565 AA732354 N71793 BQ006777 AI394289 BX648462 AA862928

AA262278 BU568939 AU130876 AI681679 AW665051 AI568916 BM680093 BM723949

BP352517 BM996916 BM701269 BG621145 AW612893 BU178653 AX748033 CK724922

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for IDE About this scheme

ExUns:	1	^	2	^	3	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17	^	18	^	19	^	20	^	21	^	22	^	23	^	24	^	25	^	26	^
SP1:																											-										-
SP2:																																			-
SP3:

ExUns:	27	^	28	^	29a	·	29b
SP1:
SP2:
SP3:

ECgene alternative splicing isoforms for IDE

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

IDE expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TGACACAGCC

About this image

IDE expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

7 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Gut Tube

Midgut

Midgut Endoderm Cells

Endoderm

Kidney

Gut Tube

Kidney

Kidney

Kidney

Reproductive System

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See IDE Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for IDE

SOURCE GeneReport for Unigene cluster: Hs.500546

SABiosciences Expression via Pathway-Focused PCR Arrays including IDE:

Alzheimer's Disease in human mouse rat

Diabetes in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for IDE Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat IDE
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat IDE
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat IDE

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IDE

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for IDE gene from 11/34 species (see all 34) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ide^{1 , 5}	insulin degrading enzyme^{1, 5}	89.04(n)¹ 95.19(a)¹		19 (32.24 cM)⁵ 15925¹ NM_031156.2¹ NP_112419.2¹ 37268743⁵
chicken (Gallus gallus)	Aves	IDE¹	insulin-degrading enzyme	83.84(n) 94.44(a)		423814 XM_421686.3 XP_421686.3
lizard (Anolis carolinensis)	Reptilia	-- --	--	89(a) 88(a)	many → 1 many → 1	GL344649.1(942-8801) GL343262.1(1888869-1946765)
African clawed frog (Xenopus laevis)	Amphibia	BJ098956.1²	--	77.72(n)		BJ098956.1
zebrafish (Danio rerio)	Actinopterygii	Dr.5554²	Transcribed sequence with moderate similarity to protein more	77.81(n)		CF348565.1
fruit fly (Drosophila melanogaster)	Insecta	Ide^{1 , 3}	proteolysis and peptidolysis insulysin³ Insulin degrading metalloproteinase¹	46(a)³ 52.68(n)¹ 46.97(a)¹		77B8³ 40248¹ NM_079458.3¹ NP_524182.3¹
worm (Caenorhabditis elegans)	Secernentea	C28F5.4³ F44E7.4¹	insulinase³ Protein F44E7.4¹	47(a) (best of 4)³ 50.05(n)¹ 43.58(a)¹		II(7520107-7523295)³ 178966¹ NM_171461.2¹ NP_741542.1¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	STE23(YLR389C)⁴ STE23¹	Metalloprotease involved, with homolog Axl1p, in N-terminal more⁴ Ste23p¹	48.83(n)¹ 39.34(a)¹		12(902660-899577)⁴ 851105^{1, 4} NP_013493.2^{1, 4}
thale cress (Arabidopsis thaliana)	eudicotyledons	AT2G41790¹	insulysin	49.34(n) 39.32(a)		818778 NM_129743.3 NP_181710.1
rice (Oryza sativa)	Liliopsida	Os07g0570300¹	hypothetical protein	49.48(n) 40.58(a)		4343659 NM_001066579.1 NP_001060044.1

ENSEMBL Gene Tree for IDE (if available)
TreeFam Gene Tree for IDE (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for IDE gene

NRD1²

1 SIMAP similar gene for IDE using alignment to 2 protein entries: IDE_HUMAN (see all proteins):

NRD1

IDE for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for IDE
PGOHUM00000258502

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 10 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs77670925^1,2	C,F,	--	87837261(+)	`ATGCTG/AACTGT`	2	--	ut3¹		1		NA	120
rs73323652^1,2	C,	--	87837525(+)	`TCTTTG/CTGGGT`	2	--	ut3¹		1		WA	2
rs7896688^1,2	C,F,H,	--	87837713(+)	`ACAATG/AAAAGC`	2	--	ut3¹		10		NS EA NA WA	1210
rs913648^1,2	C,F,O,A,H,	--	87838559(+)	`ATATCG/ATTCTT`	2	--	ut3¹ ese³		19		EA NA MN NS WA	1682
rs5786997^1,2	C	--	87838909(+)	`TATAT-/ATGTTTA`	2	--	ut3¹		0	--	--	--	--
rs77798559^1,2	C,	--	87839381(+)	`GGTAAC/GTCTGT`	2	--	ut3¹		0	--	--	--	--
rs45533535^1,2		--	87839484(+)	`CCTTAT/CATAAC`	2	--	ut3¹		1		NA	120
rs182658923^1,2	C	--	87841274(+)	`NNNNAA/CAAAAA`	2	--	int¹		0	--	--	--	--
rs12356364^1,2	C,F,H	--	87841990(+)	`AGCATC/TTACTG`	4	N D	mis¹		10		NS EA NA	1132
rs11593933^1,2	H	--	87842244(+)	`cctgtC/Ttttac`	2	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for IDE (94211441 - 94333852 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for IDE: --
Human Gene Mutation Database (HGMD): IDE

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing IDE

DNA2.0 Custom Variant and Variant Library Synthesis for IDE

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

IDE for disorders           About GeneDecksing

OMIM gene information: 146680    OMIM disorders: --

20/37 diseases for IDE (see all 37):    About MalaCards

type 2 diabetes mellitus alzheimer disease type 2 diabetes mellitus alzheimer's disease

degenerative disc disease glucose intolerance cerebral amyloid angiopathy polycystic ovary syndrome

insulin resistance liver cirrhosis down syndrome gestational diabetes

amyloidosis alzheimer disease familial brain disease colon adenocarcinoma

hyperglycemia neurodegeneration dementia insulinoma

1 disease from the University of Copenhagen DISEASES database for IDE:

Alzheimer's disease

10/18 Novoseek disease relationships for IDE gene (see all 18) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
alzheimers disease	78.8	100	10213160 (2), 15277615 (2), 16894402 (2), 16876916 (2) (see all 51)
senile plaques	67.5	9	10213160 (1), 16876916 (1), 17244626 (1), 19770104 (1) (see all 6)
late onset alzheimer disease	61.9	1	20098734 (1)
amyloid deposition	49.7	6	12941771 (1), 17047308 (1), 19073193 (1), 15750394 (1)
neurodegeneration	40.1	1	19606063 (1)
hyperinsulinemia	37.9	7	12634421 (3), 19396426 (1), 11306609 (1), 15850385 (1)
insulin resistance	37.6	10	16380485 (2), 16930758 (1), 16894402 (1), 17026490 (1) (see all 7)
niddm	34.8	17	18621727 (1), 12634421 (1), 2246195 (1), 15850385 (1) (see all 8)
hypofunction	33.3	6	12634421 (2), 15850385 (1)
dementia	28.4	12	17192720 (5), 19415148 (3), 18644361 (1)

Genetic Association Database (GAD): IDE
Human Genome Epidemiology (HuGE) Navigator: IDE (102 documents)

Export disorders for IDE gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for IDE gene, integrated from 9 sources (see all 305):
(articles sorted by number of sources associating them with IDE)

Utopia: connect your pdf to the dynamic
world of online information

Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes. (PubMed id 2293021)^{1, 2, 3, 9} Affholter J.A.... Roth R.A. (1990)
Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE. (PubMed id 17613531)^{1, 2, 9} Im H....Tang W.J. (2007)
Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. (PubMed id 17051221)^{1, 2, 9} Shen Y....Tang W.J. (2006)
Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels. (PubMed id 15277398)^{1, 4, 9} Gu H.F....Prince J.A. (2004)
Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme. (PubMed id 18986166)^{1, 2, 9} Malito E....Tang W.-J. (2008)
High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people. (PubMed id 16380485)^{1, 4, 9} Florez J.C....Groop L. (2006)
Insulin degrading enzyme is a cellular receptor mediating varicella- zoster virus infection and cell-to-cell spread. (PubMed id 17055432)^{1, 2, 9} Li Q.... Cohen J.I. (2006)
Insulin-degrading enzyme and Alzheimer disease: a genetic association study in the Han Chinese. (PubMed id 15277615)^{1, 4, 9} Bian L....He L. (2004)
Lack of association between IDE genetic variability and Down's syndrome. (PubMed id 15911128)^{1, 4, 9} Arpino C....Curatolo P. (2005)
Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzyme. (PubMed id 15858813)^{1, 4, 9} Nowotny P....Goate A. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 3416	HGNC: 5381	AceView: IDE	Ensembl:ENSG00000119912	euGenes: HUgn3416
ECgene: IDE	Kegg: 3416	H-InvDB: IDE

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for IDE	Pharmacogenomics, SNPs, Pathways

Intellectual Property for IDE gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for IDE gene:
Search GeneIP for patents involving IDE

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
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	EMD Millipore Mono- and Polyclonal Antibodies for the study of IDE
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insulin-degrading enzyme

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