IDE

Protein identityUniProt · HPA

UniProt accession

P14735

Gene

IDE

Ensembl

ENSG00000119912

Chromosome

10

Canonical length

1019 aa

Protein class

Enzymes, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted in other tissues

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1019 residues, UniProt reviewed canonical sequence.

>P14735|IDE
     1  MRYRLAWLLH PALPSTFRSV LGARLPPPER LCGFQKKTYS KMNNPAIKRI GNHITKSPED
    61  KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP PNIAGLSHFC EHMLFLGTKK
   121  YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLFDESCKD
   181  REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVRQE
   241  LLKFHSAYYS SNLMAVCVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ
   301  LYKIVPIKDI RNLYVTFPIP DLQKYYKSNP GHYLGHLIGH EGPGSLLSEL KSKGWVNTLV
   361  GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV
   421  AFRFKDKERP RGYTSKIAGI LHYYPLEEVL TAEYLLEEFR PDLIEMVLDK LRPENVRVAI
   481  VSKSFEGKTD RTEEWYGTQY KQEAIPDEVI KKWQNADLNG KFKLPTKNEF IPTNFEILPL
   541  EKEATPYPAL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL
   601  KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKIIEKMA TFEIDEKRFE
   661  IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL
   721  SRLHIEALLH GNITKQAALG IMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ
   781  QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA
   841  NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKSIEDMTEE AFQKHIQALA IRRLDKPKKL
   901  SAECAKYWGE IISQQYNFDR DNTEVAYLKT LTKEDIIKFY KEMLAVDAPR RHKVSVHVLA
   961  REMDSCPVVG EFPCQNDINL SQAPALPQPE VIQNMTEFKR GLPLFPLVKP HINFMAAKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IDE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

31 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.41

gnomAD pLI

0.01

gnomAD missense Z

2.08

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance
• amyloid-beta clearance by cellular catabolic process
• amyloid-beta metabolic process
• antigen processing and presentation of endogenous peptide antigen via MHC class I
• bradykinin catabolic process
• hormone catabolic process
• insulin catabolic process
• insulin metabolic process
• insulin receptor signaling pathway
• negative regulation of proteolysis
• peptide catabolic process
• positive regulation of protein binding
• positive regulation of protein catabolic process
• protein catabolic process
• proteolysis
• proteolysis involved in protein catabolic process
• regulation of aerobic respiration
• ubiquitin recycling

Molecular functions

• amyloid-beta binding
• ATP binding
• ATP hydrolysis activity
• endopeptidase activity
• identical protein binding
• insulin binding
• metalloendopeptidase activity
• peptide binding
• protein homodimerization activity
• protein-containing complex binding
• virus receptor activity
• zinc ion binding
• beta-endorphin binding

Cellular components

• basolateral plasma membrane
• cell surface
• cytoplasm
• cytosol
• cytosolic proteasome complex
• external side of plasma membrane
• extracellular exosome
• extracellular space
• mitochondrion
• nucleus
• peroxisomal matrix
• peroxisome

Protein domainsUniProt · Pfam · InterPro

• Peptidase M16, zinc-binding site
• Peptidase M16, C-terminal
• Metalloenzyme, LuxS/M16 peptidase-like
• Peptidase M16, N-terminal
• Peptidase M16, middle/third domain
• Peptidase M16
• Insulinase (Peptidase family M16)
• Peptidase M16 inactive domain
• Middle or third domain of peptidase_M16
• Coenzyme PQQ synthesis protein F-like, C-terminal lobe, domain 4
• PQQ synthase PqqF-like, C-terminal lobe domain 4

KeywordsUniProt

• Allosteric enzyme
• ATP-binding
• Cell membrane
• Cytoplasm
• Host cell receptor for virus entry
• Host-virus interaction
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Nucleotide-binding
• Protease
• Receptor
• Secreted
• Zinc

InteractionsUniProt · HPA

Protein binding partners of IDE in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIRT4
• IAPP
• APP