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FLASH GENE

Symbol

IDE

contributors: mct/npt - updated : 12-10-2016

HGNC name	insulin-degrading enzyme
HGNC id	5381

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10q23.33      Physical location : 94.211.440 - 94.333.852
Synonym name	insulinase
	insulysin
	insulin protease
Synonym symbol(s)	INSULYSIN, FLJ35968
EC.number	3.4.24.56

DNA

TYPE	functioning gene
STRUCTURE	120.25 kb     25 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see IFIT1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004969 25 - 5896 NP_004960 110 1018 widely Farris (2005) also called 15a or variant 1 exon 15a NM_001165946 - - 4480 NP_001159418 - 464 in brain and non-neural tissues Farris (2005) also called 15b or variant 2 exon 15b located in both cytosol and mitochondria 15b-IDE can exist as a heterodimer with the 15a isoform or as a homodimer decreased ability to degrade insulin and amyloid beta-protein

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Reproductive female system uterus     highly   male system testis     highly Respiratory respiratory tract larynx     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N terminal catalytic domain
	a C terminus facilitating substrate recognition as well as playing a key role in the oligomerization of IDE

conjugated

MetalloP

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

peptidase M16 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,cytosolic
text	zinc metalloprotease found in the cytosol of all cells (Carpenter 2010)

basic FUNCTION	may play a role in the cellular processing of insulin
	may be involved in intercellular peptide signaling
	involved in the termination of the insulin response
	involved in the clearance of insulin and amyloid-beta
	acting as a zinc metalloprotease involved in the degradation of the amyloid beta-peptide (Carpenter 2010)
	exhibits a remarkable specificity to degrade insulin without breaking the disulfide bonds that hold the insulin A and B chains together (Manolopoulou 2009)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

complex with four substrates (insulin B chain, amyloid-beta peptide (1-40), amylin and glucagon)

INTERACTION

DNA

RNA

small molecule	metal binding,
	one zinc ion per subunit

protein	binds to the nonglycosylated precursor of varicella-zoster virus gE protein found in the endoplasmic reticulum (Carpenter 2010)
	IAPP is also a known substrate of the protease insulin-degrading enzyme (IDE)

cell & other

REGULATION

inhibited by

potently by physiologically relevant concentrations of S-nitrosylation and oxidation agents (Malito 2008)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function reduction in MME and IDE activity is not the primary cause of APP accumulation in Alzheimer disease, but rather a late-stage phenomenon secondary to neurodegeneration

Susceptibility

to type 2 diabetes

Variant & Polymorphism other	polymorphisms increasing the risk of type 2 diabetes
	association of IDE polymorphisms with T2DM (Rudovich 2009)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   inhibition of IDE may represent an approach to improve glucose metabolism in human type 2 diabetes, without inducing amyloid deposition and its deleterious effects

ANIMAL & CELL MODELS