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UniProtKB - P14735 (IDE_HUMAN)

Protein

Insulin-degrading enzyme

Gene

IDE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications
(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).2 Publications

Miscellaneous

ATP-binding induces a conformation change.

Catalytic activityi

Degradation of insulin, glucagon and other polypeptides. No action on proteins.1 Publication

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Activity regulationi

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.By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi108ZincPROSITE-ProRule annotation1
Active sitei111Proton acceptorPROSITE-ProRule annotation1
Metal bindingi112ZincPROSITE-ProRule annotation1
Metal bindingi189ZincPROSITE-ProRule annotation1
Binding sitei429ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi895 – 901ATPBy similarity7

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionAllosteric enzyme, Host cell receptor for virus entry, Hydrolase, Metalloprotease, Protease, Receptor
Biological processHost-virus interaction
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.56 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-9033241 Peroxisomal protein import
SignaLinkiP14735

Protein family/group databases

MEROPSiM16.982

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-degrading enzyme (EC:3.4.24.56)
Alternative name(s):
Abeta-degrading protease
Insulin protease
Short name:
Insulinase
Insulysin
Gene namesi
Name:IDE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000119912.15
HGNCiHGNC:5381 IDE
MIMi146680 gene
neXtProtiNX_P14735

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi111E → Q: Loss of catalytic activity. 1 Publication1
Mutagenesisi132S → C: Increases catalytic rate towards INS and amyloid; when associated with C-817. 1 Publication1
Mutagenesisi184N → C: Increases catalytic rate towards INS and amyloid; when associated with C-828. 1 Publication1
Mutagenesisi426D → C: Increases catalytic rate towards INS and amyloid; when associated with C-899. 2 Publications1
Mutagenesisi817E → C: Increases catalytic rate towards INS and amyloid; when associated with C-132. 1 Publication1
Mutagenesisi828Q → C: Increases catalytic rate towards INS and amyloid; when associated with C-184. 1 Publication1
Mutagenesisi831Y → F: No effect on catalytic activity. 1
Mutagenesisi899K → C: Increases catalytic rate towards INS and amyloid; when associated with C-426. 2 Publications1

Organism-specific databases

DisGeNETi3416
OpenTargetsiENSG00000119912
PharmGKBiPA29629

Chemistry databases

ChEMBLiCHEMBL1293287
DrugBankiDB00626 Bacitracin
DB00030 Insulin Human
DB00071 Insulin Pork
GuidetoPHARMACOLOGYi2371

Polymorphism and mutation databases

BioMutaiIDE
DMDMi215274252

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000744041 – 1019Insulin-degrading enzymeAdd BLAST1019

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei192N6-succinyllysineBy similarity1
Modified residuei697N6-succinyllysineBy similarity1

Post-translational modificationi

The N-terminus is blocked.

Proteomic databases

EPDiP14735
MaxQBiP14735
PaxDbiP14735
PeptideAtlasiP14735
PRIDEiP14735
ProteomicsDBi53079

PTM databases

iPTMnetiP14735
PhosphoSitePlusiP14735

Expressioni

Gene expression databases

BgeeiENSG00000119912 Expressed in 218 organ(s), highest expression level in hair follicle
CleanExiHS_IDE
ExpressionAtlasiP14735 baseline and differential
GenevisibleiP14735 HS

Organism-specific databases

HPAiHPA063478

Interactioni

Subunit structurei

Homodimer. Can form higher oligomers.3 Publications
(Microbial infection) 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 (PubMed:17055432, PubMed:17553876).2 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109642, 90 interactors
DIPiDIP-55771N
IntActiP14735, 29 interactors
MINTiP14735
STRINGi9606.ENSP00000265986

Chemistry databases

BindingDBiP14735

Structurei

Secondary structure

11019
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP14735
SMRiP14735
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14735

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni336 – 342Substrate binding exosite7
Regioni359 – 363Substrate binding5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi853 – 858SlyX motif6

Domaini

The SlyX motif may be involved in the non-conventional secretion of the protein.By similarity

Sequence similaritiesi

Belongs to the peptidase M16 family.Curated

Phylogenomic databases

eggNOGiKOG0959 Eukaryota
COG1025 LUCA
GeneTreeiENSGT00530000063327
HOGENOMiHOG000161331
HOVERGENiHBG106799
InParanoidiP14735
KOiK01408
OMAiGIRIIVQ
OrthoDBiEOG091G0255
PhylomeDBiP14735
TreeFamiTF106275

Family and domain databases

InterProiView protein in InterPro
IPR011249 Metalloenz_LuxS/M16
IPR011765 Pept_M16_N
IPR001431 Pept_M16_Zn_BS
IPR007863 Peptidase_M16_C
IPR032632 Peptidase_M16_M
PfamiView protein in Pfam
PF00675 Peptidase_M16, 1 hit
PF05193 Peptidase_M16_C, 2 hits
PF16187 Peptidase_M16_M, 1 hit
SUPFAMiSSF63411 SSF63411, 4 hits
PROSITEiView protein in PROSITE
PS00143 INSULINASE, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P14735-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRYRLAWLLH PALPSTFRSV LGARLPPPER LCGFQKKTYS KMNNPAIKRI 
        60         70         80         90        100
GNHITKSPED KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP 
       110        120        130        140        150
PNIAGLSHFC EHMLFLGTKK YPKENEYSQF LSEHAGSSNA FTSGEHTNYY 
       160        170        180        190        200
FDVSHEHLEG ALDRFAQFFL CPLFDESCKD REVNAVDSEH EKNVMNDAWR 
       210        220        230        240        250
LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVRQE LLKFHSAYYS 
       260        270        280        290        300
SNLMAVCVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ 
       310        320        330        340        350
LYKIVPIKDI RNLYVTFPIP DLQKYYKSNP GHYLGHLIGH EGPGSLLSEL 
       360        370        380        390        400
KSKGWVNTLV GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK 
       410        420        430        440        450
LRAEGPQEWV FQECKDLNAV AFRFKDKERP RGYTSKIAGI LHYYPLEEVL 
       460        470        480        490        500
TAEYLLEEFR PDLIEMVLDK LRPENVRVAI VSKSFEGKTD RTEEWYGTQY 
       510        520        530        540        550
KQEAIPDEVI KKWQNADLNG KFKLPTKNEF IPTNFEILPL EKEATPYPAL 
       560        570        580        590        600
IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 
       610        620        630        640        650
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKIIEKMA 
       660        670        680        690        700
TFEIDEKRFE IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL 
       710        720        730        740        750
KEALDDVTLP RLKAFIPQLL SRLHIEALLH GNITKQAALG IMQMVEDTLI 
       760        770        780        790        800
EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ QRNEVHNNCG IEIYYQTDMQ 
       810        820        830        840        850
STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA NGIQGLRFII 
       860        870        880        890        900
QSEKPPHYLE SRVEAFLITM EKSIEDMTEE AFQKHIQALA IRRLDKPKKL 
       910        920        930        940        950
SAECAKYWGE IISQQYNFDR DNTEVAYLKT LTKEDIIKFY KEMLAVDAPR 
       960        970        980        990       1000
RHKVSVHVLA REMDSCPVVG EFPCQNDINL SQAPALPQPE VIQNMTEFKR 
      1010 
GLPLFPLVKP HINFMAAKL
Length:1,019
Mass (Da):117,968
Last modified:November 25, 2008 - v4
Checksum:i8A28AEF75EDA0EDA
GO
Isoform 2 (identifier: P14735-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-555: Missing.

Show »
Length:464
Mass (Da):54,240
Checksum:iD51C435A02BA4932
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T5N3Q5T5N3_HUMAN
Insulin-degrading enzyme
IDE
257Annotation score:
R4GN65R4GN65_HUMAN
Insulin-degrading enzyme
IDE
61Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti78I → M in AAA52712 (PubMed:2293021).Curated1
Sequence conflicti472R → G in BAG35668 (PubMed:14702039).Curated1
Sequence conflicti555A → V in AAA52712 (PubMed:2293021).Curated1
Sequence conflicti567 – 569FFL → KKK in AAA52712 (PubMed:2293021).Curated3
Sequence conflicti586D → G in BAG35668 (PubMed:14702039).Curated1
Sequence conflicti845G → S in AAA52712 (PubMed:2293021).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443031 – 555Missing in isoform 2. 1 PublicationAdd BLAST555

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21188 mRNA Translation: AAA52712.1
AK312810 mRNA Translation: BAG35668.1
AK316407 mRNA Translation: BAH14778.1
AL356128 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW50090.1
CH471066 Genomic DNA Translation: EAW50091.1
BC096336 mRNA Translation: AAH96336.1
BC096337 mRNA Translation: AAH96337.1
BC096339 mRNA Translation: AAH96339.1
CCDSiCCDS53554.1 [P14735-2]
CCDS7421.1 [P14735-1]
PIRiA40119 SNHUIN
RefSeqiNP_001159418.1, NM_001165946.1 [P14735-2]
NP_004960.2, NM_004969.3 [P14735-1]
UniGeneiHs.500546

Genome annotation databases

EnsembliENST00000265986; ENSP00000265986; ENSG00000119912 [P14735-1]
ENST00000371581; ENSP00000360637; ENSG00000119912 [P14735-2]
GeneIDi3416
KEGGihsa:3416
UCSCiuc001kia.4 human [P14735-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21188 mRNA Translation: AAA52712.1
AK312810 mRNA Translation: BAG35668.1
AK316407 mRNA Translation: BAH14778.1
AL356128 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW50090.1
CH471066 Genomic DNA Translation: EAW50091.1
BC096336 mRNA Translation: AAH96336.1
BC096337 mRNA Translation: AAH96337.1
BC096339 mRNA Translation: AAH96339.1
CCDSiCCDS53554.1 [P14735-2]
CCDS7421.1 [P14735-1]
PIRiA40119 SNHUIN
RefSeqiNP_001159418.1, NM_001165946.1 [P14735-2]
NP_004960.2, NM_004969.3 [P14735-1]
UniGeneiHs.500546

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2G47X-ray2.10A/B42-1019[»]
2G48X-ray2.60A/B42-1019[»]
2G49X-ray2.50A/B42-1019[»]
2G54X-ray2.25A/B42-1019[»]
2G56X-ray2.20A/B42-1019[»]
2JBUX-ray3.00A/B42-1019[»]
2JG4X-ray2.80A/B43-1019[»]
2WBYX-ray2.60A/B42-1019[»]
2WC0X-ray2.80A/B42-1019[»]
2WK3X-ray2.59A/B1-1019[»]
2YPUX-ray2.80A/B42-1019[»]
3CWWX-ray1.96A/B42-1019[»]
3E4AX-ray2.60A/B1-1019[»]
3E4ZX-ray2.28A/B42-1019[»]
3E50X-ray2.30A/B42-1019[»]
3H44X-ray3.00A/B42-1019[»]
3HGZX-ray2.91A/B43-1011[»]
3N56X-ray3.10A/B42-1019[»]
3N57X-ray3.03A/B42-1019[»]
3OFIX-ray2.35A/B42-1019[»]
3QZ2X-ray3.20A/B42-1019[»]
4DTTX-ray3.22A/B42-1019[»]
4DWKX-ray3.00A/B42-1019[»]
4GS8X-ray2.99A/B42-1019[»]
4GSCX-ray2.81A/B42-1019[»]
4GSFX-ray2.70A/B42-1019[»]
4IFHX-ray3.29A/B42-1019[»]
4IOFX-ray3.35A/B42-1019[»]
4LTEX-ray2.70A/B42-1019[»]
4M1CX-ray3.50A/B42-1019[»]
4NXOX-ray2.73A/B42-1019[»]
4PESX-ray2.21A/B42-1019[»]
4PF7X-ray2.33A/B42-1019[»]
4PF9X-ray2.50A/B42-1019[»]
4PFCX-ray2.21A/B42-1019[»]
4QIAX-ray3.20A/B42-1019[»]
4RALX-ray3.15A/B42-1019[»]
4RE9X-ray2.91A/B42-1019[»]
5CJOX-ray3.29A42-1019[»]
5UOEX-ray3.80A/B/C/D/E42-1019[»]
5WOBX-ray3.95A/B/C/D/E/F/G/H42-1019[»]
6B3Qelectron microscopy3.70A/B42-1019[»]
6B70electron microscopy3.70A/B46-1011[»]
6B7Yelectron microscopy6.50A/B46-1011[»]
6B7Zelectron microscopy6.50A/B46-1011[»]
6BF6electron microscopy6.50A/B46-1011[»]
6BF7electron microscopy6.50A/B46-1011[»]
6BF8electron microscopy4.20A/B46-1011[»]
6BF9electron microscopy7.20A/B46-1011[»]
6BFCelectron microscopy3.70A/B46-1011[»]
ProteinModelPortaliP14735
SMRiP14735
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109642, 90 interactors
DIPiDIP-55771N
IntActiP14735, 29 interactors
MINTiP14735
STRINGi9606.ENSP00000265986

Chemistry databases

BindingDBiP14735
ChEMBLiCHEMBL1293287
DrugBankiDB00626 Bacitracin
DB00030 Insulin Human
DB00071 Insulin Pork
GuidetoPHARMACOLOGYi2371

Protein family/group databases

MEROPSiM16.982

PTM databases

iPTMnetiP14735
PhosphoSitePlusiP14735

Polymorphism and mutation databases

BioMutaiIDE
DMDMi215274252

Proteomic databases

EPDiP14735
MaxQBiP14735
PaxDbiP14735
PeptideAtlasiP14735
PRIDEiP14735
ProteomicsDBi53079

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265986; ENSP00000265986; ENSG00000119912 [P14735-1]
ENST00000371581; ENSP00000360637; ENSG00000119912 [P14735-2]
GeneIDi3416
KEGGihsa:3416
UCSCiuc001kia.4 human [P14735-1]

Organism-specific databases

CTDi3416
DisGeNETi3416
EuPathDBiHostDB:ENSG00000119912.15
GeneCardsiIDE
H-InvDBiHIX0009042
HGNCiHGNC:5381 IDE
HPAiHPA063478
MIMi146680 gene
neXtProtiNX_P14735
OpenTargetsiENSG00000119912
PharmGKBiPA29629
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0959 Eukaryota
COG1025 LUCA
GeneTreeiENSGT00530000063327
HOGENOMiHOG000161331
HOVERGENiHBG106799
InParanoidiP14735
KOiK01408
OMAiGIRIIVQ
OrthoDBiEOG091G0255
PhylomeDBiP14735
TreeFamiTF106275

Enzyme and pathway databases

BRENDAi3.4.24.56 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-9033241 Peroxisomal protein import
SignaLinkiP14735

Miscellaneous databases

ChiTaRSiIDE human
EvolutionaryTraceiP14735
GeneWikiiInsulin-degrading_enzyme
GenomeRNAii3416
PROiPR:P14735
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119912 Expressed in 218 organ(s), highest expression level in hair follicle
CleanExiHS_IDE
ExpressionAtlasiP14735 baseline and differential
GenevisibleiP14735 HS

Family and domain databases

InterProiView protein in InterPro
IPR011249 Metalloenz_LuxS/M16
IPR011765 Pept_M16_N
IPR001431 Pept_M16_Zn_BS
IPR007863 Peptidase_M16_C
IPR032632 Peptidase_M16_M
PfamiView protein in Pfam
PF00675 Peptidase_M16, 1 hit
PF05193 Peptidase_M16_C, 2 hits
PF16187 Peptidase_M16_M, 1 hit
SUPFAMiSSF63411 SSF63411, 4 hits
PROSITEiView protein in PROSITE
PS00143 INSULINASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIDE_HUMAN
AccessioniPrimary (citable) accession number: P14735
Secondary accession number(s): B2R721
, B7ZAU2, D3DR35, Q5T5N2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 25, 2008
Last modified: November 7, 2018
This is version 193 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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