ID   IDE_MOUSE               Reviewed;        1019 AA.
AC   Q9JHR7;
DT   20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   14-OCT-2015, entry version 110.
DE   RecName: Full=Insulin-degrading enzyme;
DE            EC=3.4.24.56;
DE   AltName: Full=Insulin protease;
DE            Short=Insulinase;
DE   AltName: Full=Insulysin;
GN   Name=Ide;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Van Veldhoven P.P.;
RT   "Search for PTS1-containing protein in mammals.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [3]
RP   SUBCELLULAR LOCATION, IDENTIFICATION OF SLYX MOTIF, AND MUTAGENESIS OF
RP   853-GLU--TYR-858.
RX   PubMed=21576244; DOI=10.1074/jbc.C110.217893;
RA   Glebov K., Schutze S., Walter J.;
RT   "Functional relevance of a novel SlyX motif in non-conventional
RT   secretion of insulin-degrading enzyme.";
RL   J. Biol. Chem. 286:22711-22715(2011).
RN   [4]
RP   INDUCTION.
RX   PubMed=22504074; DOI=10.1016/j.febslet.2012.03.034;
RA   Zhao Y., Zhang Y., Zhou M., Wang S., Hua Z., Zhang J.;
RT   "Loss of mPer2 increases plasma insulin levels by enhanced glucose-
RT   stimulated insulin secretion and impaired insulin clearance in mice.";
RL   FEBS Lett. 586:1306-1311(2012).
RN   [5]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-192 AND LYS-697, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z.,
RA   Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Plays a role in the cellular breakdown of insulin, IAPP,
CC       glucagon, bradykinin, kallidin and other peptides, and thereby
CC       plays a role in intercellular peptide signaling. Degrades amyloid
CC       formed by APP and IAPP (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY: Degradation of insulin, glucagon and other
CC       polypeptides. No action on proteins.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- ENZYME REGULATION: Activated by ATP, other nucleotide
CC       triphosphates and small peptides. Inhibited by bacitracin (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer. Can form higher oligomers (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21576244}.
CC       Cell membrane {ECO:0000269|PubMed:21576244}. Secreted
CC       {ECO:0000269|PubMed:21576244}.
CC   -!- INDUCTION: Expression oscillates diurnally.
CC       {ECO:0000269|PubMed:22504074}.
CC   -!- DOMAIN: The SlyX motif may be involved in the non-conventional
CC       secretion of the protein.
CC   -!- MISCELLANEOUS: ATP-binding induces a conformation change.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
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DR   EMBL; AJ278422; CAC01233.1; -; mRNA.
DR   UniGene; Mm.28366; -.
DR   ProteinModelPortal; Q9JHR7; -.
DR   SMR; Q9JHR7; 42-1011.
DR   DIP; DIP-60044N; -.
DR   STRING; 10090.ENSMUSP00000121358; -.
DR   ChEMBL; CHEMBL3232680; -.
DR   MEROPS; M16.982; -.
DR   PhosphoSite; Q9JHR7; -.
DR   MaxQB; Q9JHR7; -.
DR   PaxDb; Q9JHR7; -.
DR   PRIDE; Q9JHR7; -.
DR   MGI; MGI:96412; Ide.
DR   eggNOG; COG1025; -.
DR   HOVERGEN; HBG106799; -.
DR   InParanoid; Q9JHR7; -.
DR   ChiTaRS; Ide; mouse.
DR   PRO; PR:Q9JHR7; -.
DR   Proteomes; UP000000589; Unplaced.
DR   CleanEx; MM_IDE; -.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005782; C:peroxisomal matrix; IBA:GO_Central.
DR   GO; GO:0005777; C:peroxisome; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0001948; F:glycoprotein binding; ISO:MGI.
DR   GO; GO:0043559; F:insulin binding; ISO:MGI.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0042277; F:peptide binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0005102; F:receptor binding; ISO:MGI.
DR   GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0050435; P:beta-amyloid metabolic process; ISS:UniProtKB.
DR   GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB.
DR   GO; GO:0008340; P:determination of adult lifespan; ISO:MGI.
DR   GO; GO:0042447; P:hormone catabolic process; IBA:GO_Central.
DR   GO; GO:1901143; P:insulin catabolic process; ISO:MGI.
DR   GO; GO:1901142; P:insulin metabolic process; ISO:MGI.
DR   GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR   GO; GO:0032461; P:positive regulation of protein oligomerization; ISO:MGI.
DR   GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR   GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; ISO:MGI.
DR   GO; GO:0051603; P:proteolysis involved in cellular protein catabolic process; ISO:MGI.
DR   GO; GO:0010992; P:ubiquitin homeostasis; ISO:MGI.
DR   Gene3D; 3.30.830.10; -; 4.
DR   InterPro; IPR011249; Metalloenz_LuxS/M16.
DR   InterPro; IPR011237; Pept_M16_dom.
DR   InterPro; IPR011765; Pept_M16_N.
DR   InterPro; IPR001431; Pept_M16_Zn_BS.
DR   InterPro; IPR007863; Peptidase_M16_C.
DR   Pfam; PF00675; Peptidase_M16; 1.
DR   Pfam; PF05193; Peptidase_M16_C; 2.
DR   SUPFAM; SSF63411; SSF63411; 4.
DR   PROSITE; PS00143; INSULINASE; 1.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Cell membrane; Complete proteome;
KW   Cytoplasm; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW   Nucleotide-binding; Protease; Reference proteome; Secreted; Zinc.
FT   CHAIN         1   1019       Insulin-degrading enzyme.
FT                                /FTId=PRO_0000074405.
FT   NP_BIND     895    901       ATP. {ECO:0000250}.
FT   MOTIF       853    858       SlyX motif.
FT   ACT_SITE    111    111       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10096}.
FT   METAL       108    108       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10096}.
FT   METAL       112    112       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10096}.
FT   METAL       189    189       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU10096}.
FT   BINDING     429    429       ATP. {ECO:0000250}.
FT   MOD_RES     192    192       N6-succinyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MOD_RES     697    697       N6-succinyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MUTAGEN     853    858       Missing: Marked decrease in secretion.
FT                                {ECO:0000269|PubMed:21576244}.
SQ   SEQUENCE   1019 AA;  117772 MW;  9443A6886110BE86 CRC64;
     MRNGLVWLLH PALPGTLRSI LGARPPPAKR LCGFPKQTYS TMSNPAIQRI EDQIVKSPED
     KREYRGLELA NGIKVLLISD PTTDKSSAAL DVHIGSLSDP PNIPGLSHFC EHMLFLGTKK
     YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLLDASCKD
     REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVREE
     LLKFHSTYYS SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLRQ
     LYKIVPIKDI RNLYVTFPIP DLQQYYKSNP GYYLGHLIGH EGPGSLLSEL KSKGWVNTLV
     GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV
     AFRFKDKERP RGYTSKIAGK LHYYPLNGVL TAEYLLEEFR PDLIDMVLDK LRPENVRVAI
     VSKSFEGKTD RTEQWYGTQY KQEAIPEDVI QKWQNADLNG KFKLPTKNEF IPTNFEILSL
     EKDATPYPAL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL
     KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKRYNDKQPI LLKKITEKMA TFEIDKKRFE
     IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL
     SRLHIEALLH GNITKQAALG VMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ
     QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA
     NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKAIEDMTEE AFQKHIQALA IRRLDKPKKL
     SAECAKYWGE IISQQYNYDR DNIEVAYLKT LTKDDIIRFY QEMLAVDAPR RHKVSVHVLA
     REMDSCPVVG EFPSQNDINL SEAPPLPQPE VIHNMTEFKR GLPLFPLVKP HINFMAAKL
//