Q9JHR7 (IDE_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-degrading enzyme
EC=3.4.24.56

Alternative name(s):
Insulin protease
Short name=Insulinase
Insulysin

Gene names

Name:

Ide

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1019 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Catalytic activity	Degradation of insulin, glucagon and other polypeptides. No action on proteins.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Activated by ATP, other nucleotide triphosphates and small peptides. Inhibited by bacitracin By similarity.
Subunit structure	Homodimer. Can form higher oligomers By similarity.
Subcellular location	Cytoplasm. Cell membrane. Secreted Ref.2.
Domain	The SlyX motif may be involved in the non-conventional secretion of the protein.
Miscellaneous	ATP-binding induces a conformation change By similarity.
Sequence similarities	Belongs to the peptidase M16 family.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Secreted
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	beta-amyloid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB bradykinin catabolic process Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 18614015. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB metalloendopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1019	1019	Insulin-degrading enzyme		PRO_0000074405
Regions
	Nucleotide binding	895 – 901	7	ATP By similarity
	Motif	853 – 858	6	SlyX motif
Sites
	Active site	111	1	Proton acceptor By similarity
	Metal binding	108	1	Zinc By similarity
	Metal binding	112	1	Zinc By similarity
	Metal binding	189	1	Zinc By similarity
	Binding site	429	1	ATP By similarity
Experimental info
	Mutagenesis	853 – 858	6	Missing: Marked decrease in secretion. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9JHR7 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 9443A6886110BE86	FASTA	1,019	117,772
	10 20 30 40 50 60 MRNGLVWLLH PALPGTLRSI LGARPPPAKR LCGFPKQTYS TMSNPAIQRI EDQIVKSPED 70 80 90 100 110 120 KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP PNIPGLSHFC EHMLFLGTKK 130 140 150 160 170 180 YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLLDASCKD 190 200 210 220 230 240 REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE 250 260 270 280 290 300 LLKFHSTYYS SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLRQ 310 320 330 340 350 360 LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GYYLGHLIGH EGPGSLLSEL KSKGWVNTLV 370 380 390 400 410 420 GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV 430 440 450 460 470 480 AFRFKDKERP RGYTSKIAGK LHYYPLNGVL TAEYLLEEFR PDLIDMVLDK LRPENVRVAI 490 500 510 520 530 540 VSKSFEGKTD RTEQWYGTQY KQEAIPEDVI QKWQNADLNG KFKLPTKNEF IPTNFEILSL 550 560 570 580 590 600 EKDATPYPAL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL 610 620 630 640 650 660 KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKRYNDKQPI LLKKITEKMA TFEIDKKRFE 670 680 690 700 710 720 IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL 730 740 750 760 770 780 SRLHIEALLH GNITKQAALG VMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ 790 800 810 820 830 840 QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA 850 860 870 880 890 900 NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKAIEDMTEE AFQKHIQALA IRRLDKPKKL 910 920 930 940 950 960 SAECAKYWGE IISQQYNYDR DNIEVAYLKT LTKDDIIRFY QEMLAVDAPR RHKVSVHVLA 970 980 990 1000 1010 REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR GLPLFPLVKP HINFMAAKL

References

[1]	"Search for PTS1-containing protein in mammals." Van Veldhoven P.P. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Functional relevance of a novel SlyX motif in non-conventional secretion of insulin-degrading enzyme." Glebov K., Schutze S., Walter J. J. Biol. Chem. 286:22711-22715(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION OF SLYX MOTIF, MUTAGENESIS OF 853-GLU--TYR-858.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ278422 mRNA. Translation: CAC01233.1.
IPI	IPI00119784.
UniGene	Mm.28366.
3D structure databases
ProteinModelPortal	Q9JHR7.
SMR	Q9JHR7. Positions 42-1011.
ModBase	Search...
Protein family/group databases
MEROPS	M16.002.
PTM databases
PhosphoSite	Q9JHR7.
Proteomic databases
PaxDb	Q9JHR7.
PRIDE	Q9JHR7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:96412. Ide.
Phylogenomic databases
eggNOG	COG1025.
HOVERGEN	HBG106799.
InParanoid	Q9JHR7.
Gene expression databases
CleanEx	MM_IDE.
Genevestigator	Q9JHR7.
GermOnline	ENSMUSG00000056999. Mus musculus.
Family and domain databases
Gene3D	3.30.830.10. 4 hits.
InterPro	IPR011249. Metalloenz_LuxS/M16. IPR011237. Pept_M16_dom. IPR011765. Pept_M16_N. IPR001431. Pept_M16_Zn_BS. IPR007863. Peptidase_M16_C. [Graphical view]
Pfam	PF00675. Peptidase_M16. 1 hit. PF05193. Peptidase_M16_C. 2 hits. [Graphical view]
SUPFAM	SSF63411. Metalloenz_metal-bd. 4 hits.
PROSITE	PS00143. INSULINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IDE. mouse.
SOURCE	Search...

Entry information

Entry name

IDE_MOUSE

Accession

Primary (citable) accession number: Q9JHR7

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	October 1, 2000
Last modified:	April 3, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program