Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P14735

- IDE_HUMAN

UniProt

P14735 - IDE_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Insulin-degrading enzyme

Gene

IDE

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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

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

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi108 – 1081ZincPROSITE-ProRule annotation
Active sitei111 – 1111Proton acceptorPROSITE-ProRule annotation
Metal bindingi112 – 1121ZincPROSITE-ProRule annotation
Metal bindingi189 – 1891ZincPROSITE-ProRule annotation
Binding sitei429 – 4291ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi895 – 9017ATPBy similarity

GO - Molecular functioni

  1. ATPase activity Source: Ensembl
  2. ATP binding Source: UniProtKB
  3. beta-amyloid binding Source: Ensembl
  4. beta-endorphin binding Source: Ensembl
  5. glycoprotein binding Source: UniProtKB
  6. insulin binding Source: UniProtKB
  7. metalloendopeptidase activity Source: UniProtKB
  8. peptide binding Source: UniProtKB
  9. protein homodimerization activity Source: UniProtKB
  10. receptor binding Source: UniProtKB
  11. ubiquitin binding Source: UniProtKB
  12. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-amyloid metabolic process Source: UniProtKB
  2. bradykinin catabolic process Source: UniProtKB
  3. determination of adult lifespan Source: UniProtKB
  4. hormone catabolic process Source: Ensembl
  5. insulin catabolic process Source: UniProtKB
  6. insulin metabolic process Source: UniProtKB
  7. insulin receptor signaling pathway Source: UniProtKB
  8. negative regulation of proteolysis Source: Ensembl
  9. positive regulation of protein oligomerization Source: UniProtKB
  10. protein heterooligomerization Source: Ensembl
  11. protein homooligomerization Source: UniProtKB
  12. protein homotetramerization Source: Ensembl
  13. proteolysis Source: UniProtKB
  14. proteolysis involved in cellular protein catabolic process Source: UniProtKB
  15. ubiquitin homeostasis Source: UniProtKB
  16. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Host-virus interaction

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

SignaLinkiP14735.

Protein family/group databases

MEROPSiM16.002.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:5381. IDE.

Subcellular locationi

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.

GO - Cellular componenti

  1. cell surface Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. cytosolic proteasome complex Source: Ensembl
  5. extracellular space Source: UniProtKB
  6. mitochondrion Source: UniProtKB
  7. nucleus Source: UniProtKB
  8. peroxisomal matrix Source: Ensembl
  9. peroxisome Source: UniProtKB
  10. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi111 – 1111E → Q: Loss of catalytic activity. 1 Publication
Mutagenesisi132 – 1321S → C: Increases catalytic rate towards INS and amyloid; when associated with C-817. 1 Publication
Mutagenesisi184 – 1841N → C: Increases catalytic rate towards INS and amyloid; when associated with C-828. 1 Publication
Mutagenesisi426 – 4261D → C: Increases catalytic rate towards INS and amyloid; when associated with C-899. 2 Publications
Mutagenesisi817 – 8171E → C: Increases catalytic rate towards INS and amyloid; when associated with C-132. 1 Publication
Mutagenesisi828 – 8281Q → C: Increases catalytic rate towards INS and amyloid; when associated with C-184. 1 Publication
Mutagenesisi831 – 8311Y → F: No effect on catalytic activity.
Mutagenesisi899 – 8991K → C: Increases catalytic rate towards INS and amyloid; when associated with C-426. 2 Publications

Organism-specific databases

PharmGKBiPA29629.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10191019Insulin-degrading enzymePRO_0000074404Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei192 – 1921N6-succinyllysineBy similarity
Modified residuei697 – 6971N6-succinyllysineBy similarity

Post-translational modificationi

The N-terminus is blocked.

Proteomic databases

MaxQBiP14735.
PaxDbiP14735.
PRIDEiP14735.

PTM databases

PhosphoSiteiP14735.

Expressioni

Gene expression databases

BgeeiP14735.
CleanExiHS_IDE.
ExpressionAtlasiP14735. baseline and differential.
GenevestigatoriP14735.

Organism-specific databases

HPAiCAB012303.

Interactioni

Subunit structurei

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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCL3P101473EBI-2556886,EBI-8459634

Protein-protein interaction databases

BioGridi109642. 30 interactions.
DIPiDIP-55771N.
IntActiP14735. 5 interactions.
MINTiMINT-2801173.
STRINGi9606.ENSP00000265986.

Structurei

Secondary structure

1
1019
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi47 – 504Combined sources
Beta strandi63 – 697Combined sources
Beta strandi74 – 796Combined sources
Beta strandi84 – 9310Combined sources
Helixi96 – 983Combined sources
Beta strandi101 – 1033Combined sources
Helixi106 – 1138Combined sources
Helixi114 – 1163Combined sources
Beta strandi118 – 1214Combined sources
Helixi126 – 1327Combined sources
Turni133 – 1353Combined sources
Beta strandi137 – 1426Combined sources
Beta strandi147 – 1548Combined sources
Helixi155 – 1573Combined sources
Helixi158 – 1669Combined sources
Helixi167 – 1693Combined sources
Helixi176 – 19419Combined sources
Helixi197 – 20711Combined sources
Helixi214 – 2163Combined sources
Helixi223 – 2264Combined sources
Helixi228 – 2325Combined sources
Helixi237 – 24812Combined sources
Helixi251 – 2533Combined sources
Beta strandi254 – 2629Combined sources
Helixi264 – 27512Combined sources
Helixi295 – 2973Combined sources
Beta strandi298 – 3047Combined sources
Beta strandi307 – 3093Combined sources
Beta strandi312 – 3198Combined sources
Helixi323 – 3253Combined sources
Turni326 – 3283Combined sources
Helixi330 – 3389Combined sources
Helixi346 – 3527Combined sources
Beta strandi359 – 3679Combined sources
Beta strandi370 – 3789Combined sources
Helixi381 – 3855Combined sources
Helixi387 – 40418Combined sources
Helixi408 – 42316Combined sources
Helixi430 – 44011Combined sources
Turni441 – 4433Combined sources
Helixi446 – 4483Combined sources
Turni449 – 4546Combined sources
Helixi461 – 4688Combined sources
Helixi473 – 4753Combined sources
Beta strandi477 – 4815Combined sources
Helixi483 – 4853Combined sources
Turni486 – 4883Combined sources
Turni494 – 4963Combined sources
Beta strandi499 – 5046Combined sources
Helixi507 – 5148Combined sources
Beta strandi549 – 5535Combined sources
Beta strandi555 – 5639Combined sources
Beta strandi565 – 5673Combined sources
Beta strandi570 – 57910Combined sources
Helixi581 – 5833Combined sources
Beta strandi584 – 5863Combined sources
Helixi587 – 61327Combined sources
Beta strandi616 – 6238Combined sources
Beta strandi626 – 63510Combined sources
Helixi638 – 65013Combined sources
Helixi656 – 67217Combined sources
Helixi673 – 6753Combined sources
Helixi678 – 69013Combined sources
Beta strandi691 – 6933Combined sources
Helixi697 – 7048Combined sources
Helixi709 – 72113Combined sources
Beta strandi722 – 73211Combined sources
Helixi735 – 75319Combined sources
Helixi760 – 7623Combined sources
Beta strandi775 – 7828Combined sources
Beta strandi787 – 79913Combined sources
Helixi802 – 82322Combined sources
Turni824 – 8274Combined sources
Beta strandi831 – 84010Combined sources
Beta strandi843 – 85412Combined sources
Helixi856 – 87621Combined sources
Helixi879 – 89416Combined sources
Helixi900 – 91213Combined sources
Helixi920 – 9289Combined sources
Helixi933 – 94311Combined sources
Beta strandi952 – 9598Combined sources
Beta strandi990 – 9923Combined sources
Helixi995 – 10006Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4QLDX-ray3.20A/B42-1019[»]
ProteinModelPortaliP14735.
SMRiP14735. Positions 43-1016.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14735.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni336 – 3427Substrate binding exosite
Regioni359 – 3635Substrate binding

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi853 – 8586SlyX motif

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

eggNOGiCOG1025.
GeneTreeiENSGT00530000063327.
HOGENOMiHOG000161331.
HOVERGENiHBG106799.
InParanoidiP14735.
KOiK01408.
OMAiSIFHIIK.
OrthoDBiEOG7HHWRD.
PhylomeDBiP14735.
TreeFamiTF106275.

Family and domain databases

Gene3Di3.30.830.10. 4 hits.
InterProiIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 4 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti78 – 781I → M in AAA52712. (PubMed:2293021)Curated
Sequence conflicti472 – 4721R → G in BAG35668. (PubMed:14702039)Curated
Sequence conflicti555 – 5551A → V in AAA52712. (PubMed:2293021)Curated
Sequence conflicti567 – 5693FFL → KKK in AAA52712. (PubMed:2293021)Curated
Sequence conflicti586 – 5861D → G in BAG35668. (PubMed:14702039)Curated
Sequence conflicti845 – 8451G → S in AAA52712. (PubMed:2293021)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti612 – 6121E → K.
Corresponds to variant rs2229708 [ dbSNP | Ensembl ].
VAR_051571

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 555555Missing in isoform 2. 1 PublicationVSP_044303Add
BLAST

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. Translation: CAI13670.1.
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.3. human. [P14735-1]
uc010qnp.2. human. [P14735-2]

Polymorphism databases

DMDMi215274252.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAI13670.1 .
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 .
CCDSi CCDS53554.1. [P14735-2 ]
CCDS7421.1. [P14735-1 ]
PIRi A40119. SNHUIN.
RefSeqi NP_001159418.1. NM_001165946.1. [P14735-2 ]
NP_004960.2. NM_004969.3. [P14735-1 ]
UniGenei Hs.500546.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2G47 X-ray 2.10 A/B 42-1019 [» ]
2G48 X-ray 2.60 A/B 42-1019 [» ]
2G49 X-ray 2.50 A/B 42-1019 [» ]
2G54 X-ray 2.25 A/B 42-1019 [» ]
2G56 X-ray 2.20 A/B 42-1019 [» ]
2JBU X-ray 3.00 A/B 42-1019 [» ]
2JG4 X-ray 2.80 A/B 43-1019 [» ]
2WBY X-ray 2.60 A/B 42-1019 [» ]
2WC0 X-ray 2.80 A/B 42-1019 [» ]
2WK3 X-ray 2.59 A/B 1-1019 [» ]
2YPU X-ray 2.80 A/B 42-1019 [» ]
3CWW X-ray 1.96 A/B 42-1019 [» ]
3E4A X-ray 2.60 A/B 1-1019 [» ]
3E4Z X-ray 2.28 A/B 42-1019 [» ]
3E50 X-ray 2.30 A/B 42-1019 [» ]
3H44 X-ray 3.00 A/B 42-1019 [» ]
3HGZ X-ray 2.91 A/B 43-1011 [» ]
3N56 X-ray 3.10 A/B 42-1019 [» ]
3N57 X-ray 3.03 A/B 42-1019 [» ]
3OFI X-ray 2.35 A/B 42-1019 [» ]
3QZ2 X-ray 3.20 A/B 42-1019 [» ]
4DTT X-ray 3.22 A/B 42-1019 [» ]
4DWK X-ray 3.00 A/B 42-1019 [» ]
4GS8 X-ray 2.99 A/B 42-1019 [» ]
4GSC X-ray 2.81 A/B 42-1019 [» ]
4GSF X-ray 2.70 A/B 42-1019 [» ]
4IFH X-ray 3.29 A/B 42-1019 [» ]
4IOF X-ray 3.35 A/B 42-1019 [» ]
4LTE X-ray 2.70 A/B 42-1019 [» ]
4M1C X-ray 3.50 A/B 42-1019 [» ]
4QLD X-ray 3.20 A/B 42-1019 [» ]
ProteinModelPortali P14735.
SMRi P14735. Positions 43-1016.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109642. 30 interactions.
DIPi DIP-55771N.
IntActi P14735. 5 interactions.
MINTi MINT-2801173.
STRINGi 9606.ENSP00000265986.

Chemistry

BindingDBi P14735.
ChEMBLi CHEMBL1293287.
DrugBanki DB00071. "Insulin.
DB00626. Bacitracin.
DB00030. Insulin Regular.

Protein family/group databases

MEROPSi M16.002.

PTM databases

PhosphoSitei P14735.

Polymorphism databases

DMDMi 215274252.

Proteomic databases

MaxQBi P14735.
PaxDbi P14735.
PRIDEi P14735.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000265986 ; ENSP00000265986 ; ENSG00000119912 . [P14735-1 ]
ENST00000371581 ; ENSP00000360637 ; ENSG00000119912 . [P14735-2 ]
GeneIDi 3416.
KEGGi hsa:3416.
UCSCi uc001kia.3. human. [P14735-1 ]
uc010qnp.2. human. [P14735-2 ]

Organism-specific databases

CTDi 3416.
GeneCardsi GC10M094211.
H-InvDB HIX0009042.
HGNCi HGNC:5381. IDE.
HPAi CAB012303.
MIMi 146680. gene.
neXtProti NX_P14735.
PharmGKBi PA29629.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1025.
GeneTreei ENSGT00530000063327.
HOGENOMi HOG000161331.
HOVERGENi HBG106799.
InParanoidi P14735.
KOi K01408.
OMAi SIFHIIK.
OrthoDBi EOG7HHWRD.
PhylomeDBi P14735.
TreeFami TF106275.

Enzyme and pathway databases

SignaLinki P14735.

Miscellaneous databases

EvolutionaryTracei P14735.
GeneWikii Insulin-degrading_enzyme.
GenomeRNAii 3416.
NextBioi 13466.
PROi P14735.
SOURCEi Search...

Gene expression databases

Bgeei P14735.
CleanExi HS_IDE.
ExpressionAtlasi P14735. baseline and differential.
Genevestigatori P14735.

Family and domain databases

Gene3Di 3.30.830.10. 4 hits.
InterProi IPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view ]
Pfami PF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view ]
SUPFAMi SSF63411. SSF63411. 4 hits.
PROSITEi PS00143. INSULINASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III."
    Affholter J.A., Fried V.A., Roth R.A.
    Science 242:1415-1418(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
  2. "Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes."
    Affholter J.A., Hsieh C.L., Francke U., Roth R.A.
    Mol. Endocrinol. 4:1125-1135(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Testis.
  4. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. "Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme."
    Vekrellis K., Ye Z., Qiu W.Q., Walsh D., Hartley D., Chesneau V., Rosner M.R., Selkoe D.J.
    J. Neurosci. 20:1657-1665(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  8. "Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread."
    Li Q., Ali M.A., Cohen J.I.
    Cell 127:305-316(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH VZV GLYCOPROTEIN E.
  9. "The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for binding to insulin-degrading enzyme, a VZV receptor."
    Li Q., Krogmann T., Ali M.A., Tang W.-J., Cohen J.I.
    J. Virol. 81:8525-8532(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VZV GLYCOPROTEIN E.
  10. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism."
    Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.
    Nature 443:870-874(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 42-1019 OF MUTANT GLN-111 IN COMPLEXES WITH ZINC IONS; IAPP; INSULIN; AMYLOID AND GLUCAGON, MUTAGENESIS OF GLU-111; SER-132; ASN-184; ASP-426; GLU-817; GLN-828 AND LYS-899, COFACTOR, SUBUNIT, ACTIVE SITE.
  14. "Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE."
    Im H., Manolopoulou M., Malito E., Shen Y., Zhao J., Neant-Fery M., Sun C.-Y., Meredith S.C., Sisodia S.S., Leissring M.A., Tang W.-J.
    J. Biol. Chem. 282:25453-25463(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 43-1018 OF MUTANT PHE-831 IN COMPLEX WITH ZINC IONS AND SUBSTRATE PEPTIDE, CATALYTIC ACTIVITY, ENZYME REGULATION, ATP-BINDING, SUBUNIT, MUTAGENESIS OF ASP-426 AND LYS-899, FUNCTION.
  15. "Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme."
    Malito E., Ralat L.A., Manolopoulou M., Tsay J.L., Wadlington N.L., Tang W.-J.
    Biochemistry 47:12822-12834(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 42-1019 OF MUTANT GLN-111 IN COMPLEX WITH BRADYKININ, FUNCTION, ENZYME REGULATION.

Entry informationi

Entry nameiIDE_HUMAN
AccessioniPrimary (citable) accession number: P14735
Secondary accession number(s): B2R721
, B7ZAU2, D3DR35, Q5T5N2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 25, 2008
Last modified: November 26, 2014
This is version 152 of the entry and version 4 of the sequence. [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

Miscellaneous

ATP-binding induces a conformation change.

Keywords - Technical termi

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

Documents

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

External Data

Dasty 3