IDE_DROME
ID IDE_DROME Reviewed; 990 AA.
AC P22817; B9EQR9; Q86MR2; Q95S06; Q9VPG8;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 159.
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; ORFNames=CG5517;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2126597; DOI=10.1210/mend-4-10-1580;
RA Kuo W.L., Gehm B.D., Rosner M.R.;
RT "Cloning and expression of the cDNA for a Drosophila insulin-degrading
RT enzyme.";
RL Mol. Endocrinol. 4:1580-1591(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Booth B.,
RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E.,
RA George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G.,
RA Miranda A., Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S.,
RA Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M.,
RA Celniker S.E.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 663-990.
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP PROTEIN SEQUENCE OF 2-16, FUNCTION, INDUCTION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=3139025; DOI=10.1021/bi00412a006;
RA Garcia J.V., Fenton B.W., Rosner M.R.;
RT "Isolation and characterization of an insulin-degrading enzyme from
RT Drosophila melanogaster.";
RL Biochemistry 27:4237-4244(1988).
CC -!- FUNCTION: Can cleave insulin and TGF-alpha.
CC {ECO:0000269|PubMed:3139025}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Degradation of insulin, glucagon and other polypeptides. No
CC action on proteins.; EC=3.4.24.56;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:3139025};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:3139025};
CC -!- INDUCTION: Inhibited by bacitracin and sulfhydryl-specific reagents.
CC {ECO:0000269|PubMed:3139025}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL28563.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAO74689.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ACM16704.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M58465; AAA28439.1; -; mRNA.
DR EMBL; AE014296; AAF51584.3; -; Genomic_DNA.
DR EMBL; BT006006; AAO74689.1; ALT_INIT; mRNA.
DR EMBL; BT057994; ACM16704.1; ALT_INIT; mRNA.
DR EMBL; AY061015; AAL28563.1; ALT_INIT; mRNA.
DR PIR; A37254; SNFFIN.
DR RefSeq; NP_524182.3; NM_079458.4.
DR AlphaFoldDB; P22817; -.
DR SMR; P22817; -.
DR BioGRID; 65508; 6.
DR IntAct; P22817; 1.
DR STRING; 7227.FBpp0271781; -.
DR MEROPS; M16.A08; -.
DR PaxDb; P22817; -.
DR PRIDE; P22817; -.
DR DNASU; 40248; -.
DR EnsemblMetazoa; FBtr0273273; FBpp0271781; FBgn0001247.
DR GeneID; 40248; -.
DR KEGG; dme:Dmel_CG5517; -.
DR CTD; 3416; -.
DR FlyBase; FBgn0001247; Ide.
DR VEuPathDB; VectorBase:FBgn0001247; -.
DR eggNOG; KOG0959; Eukaryota.
DR GeneTree; ENSGT00940000155780; -.
DR HOGENOM; CLU_004639_1_1_1; -.
DR InParanoid; P22817; -.
DR OMA; WIFDEMK; -.
DR OrthoDB; 1008844at2759; -.
DR PhylomeDB; P22817; -.
DR BRENDA; 3.4.24.56; 1994.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR Reactome; R-DME-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 40248; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Ide; fly.
DR GenomeRNAi; 40248; -.
DR PRO; PR:P22817; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0001247; Expressed in eye disc (Drosophila) and 25 other tissues.
DR Genevisible; P22817; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005777; C:peroxisome; ISS:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:FlyBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; HMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:1901143; P:insulin catabolic process; IDA:FlyBase.
DR GO; GO:0048640; P:negative regulation of developmental growth; IMP:FlyBase.
DR GO; GO:0045926; P:negative regulation of growth; IMP:FlyBase.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IGI:FlyBase.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR GO; GO:0045089; P:positive regulation of innate immune response; HMP:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0046662; P:regulation of oviposition; IMP:FlyBase.
DR GO; GO:0090062; P:regulation of trehalose metabolic process; IDA:FlyBase.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR001431; Pept_M16_Zn_BS.
DR InterPro; IPR007863; Peptidase_M16_C.
DR InterPro; IPR032632; Peptidase_M16_M.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 2.
DR Pfam; PF16187; Peptidase_M16_M; 1.
DR SUPFAM; SSF63411; SSF63411; 4.
DR PROSITE; PS00143; INSULINASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3139025"
FT CHAIN 2..990
FT /note="Insulin-degrading enzyme"
FT /id="PRO_0000074407"
FT ACT_SITE 84
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 85
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT CONFLICT 11
FT /note="A -> V (in Ref. 1; AAA28439)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="N -> D (in Ref. 4; AAO74689)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="F -> L (in Ref. 1; AAA28439)"
FT /evidence="ECO:0000305"
FT CONFLICT 402..403
FT /note="QP -> ES (in Ref. 1; AAA28439)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="Q -> K (in Ref. 1; AAA28439)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="R -> S (in Ref. 1; AAA28439)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 990 AA; 113684 MW; 32D19736CB497DCB CRC64;
MTIAESSQKS ATRKPDSMEP ILRLNNIEKS LQDTRDYRGL QLENGLKVLL ISDPNTDVSA
AALSVQVGHM SDPTNLPGLA HFCEHMLFLG TEKYPHENGY TTYLSQSGGS SNAATYPLMT
KYHFHVAPDK LDGALDRFAQ FFIAPLFTPS ATEREINAVN SEHEKNLPSD LWRIKQVNRH
LAKPDHAYSK FGSGNKTTLS EIPKSKNIDV RDELLKFHKQ WYSANIMCLA VIGKESLDEL
EGMVLEKFSE IENKNVKVPG WPRHPYAEER YGQKVKIVPI KDIRSLTISF TTDDLTQFYK
SGPDNYLTHL IGHEGKGSIL SELRRLGWCN DLMAGHQNTQ NGFGFFDIVV DLTQEGLEHV
DDIVKIVFQY LEMLRKEGPK KWIFDECVKL NEMRFRFKEK EQPENLVTHA VSSMQIFPLE
EVLIAPYLSN EWRPDLIKGL LDELVPSKSR IVIVSQSFEP DCDLAEPYYK TKYGITRVAK
DTVQSWENCE LNENLKLALP NSFIPTNFDI SDVPADAPKH PTIILDTPIL RVWHKQDNQF
NKPKACMTFD MSNPIAYLDP LNCNLNHMMV MLLKDQLNEY LYDAELASLK LSVMGKSCGI
DFTIRGFSDK QVVLLEKLLD HLFDFSIDEK RFDILKEEYV RSLKNFKAEQ PYQHSIYYLA
LLLTENAWAN MELLDAMELV TYDRVLNFAK EFFQRLHTEC FIFGNVTKQQ ATDIAGRVNT
RLEATNASKL PILARQMLKK REYKLLAGDS YLFEKENEFH KSSCAQLYLQ CGAQTDHTNI
MVNLVSQVLS EPCYDCLRTK EQLGYIVFSG VRKVNGANGI RIIVQSAKHP SYVEDRIENF
LQTYLQVIED MPLDEFERHK EALAVKKLEK PKTIFQQFSQ FYGEIAMQTY HFEREEAEVA
ILRKISKADF VDYFKKFIAK DGEERRVLSV HIVSQQTDEN ATSEAEPVEI TNMERHKPIS
DIVTFKSCKE LYPIALPFLD IKAKGARSKL
