P22817 (IDE_DROME) 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
ORF Names:	CG5517

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	990 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Can cleave insulin and TGF-alpha. Ref.6
Catalytic activity	Degradation of insulin, glucagon and other polypeptides. No action on proteins.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Induction	Inhibited by bacitracin and sulfhydryl-specific reagents. Ref.6
Sequence similarities	Belongs to the peptidase M16 family.
Biophysicochemical properties	pH dependence: Optimum pH is 7-8. Ref.6 Temperature dependence: Optimum temperature is 37 degrees Celsius.
Sequence caution	The sequence AAL28563.1 differs from that shown. Reason: Erroneous initiation. The sequence AAO74689.1 differs from that shown. Reason: Erroneous initiation. The sequence ACM16704.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	determination of adult lifespan Inferred from mutant phenotype PubMed 20493190PubMed 21212741. Source: FlyBase negative regulation of growth Inferred from mutant phenotype PubMed 20493190. Source: FlyBase proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of oviposition Inferred from mutant phenotype PubMed 21212741. Source: FlyBase regulation of trehalose metabolic process Inferred from direct assay PubMed 21212741. Source: FlyBase
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 990	989	Insulin-degrading enzyme		PRO_0000074407
Sites
	Active site	84	1	Proton acceptor By similarity
	Metal binding	81	1	Zinc By similarity
	Metal binding	85	1	Zinc By similarity
	Metal binding	162	1	Zinc By similarity
Experimental info
	Sequence conflict	11	1	A → V in AAA28439. Ref.1
	Sequence conflict	178	1	N → D in AAO74689. Ref.4
	Sequence conflict	384	1	F → L in AAA28439. Ref.1
	Sequence conflict	402 – 403	2	QP → ES in AAA28439. Ref.1
	Sequence conflict	415	1	Q → K in AAA28439. Ref.1
	Sequence conflict	433	1	R → S in AAA28439. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P22817 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 32D19736CB497DCB	FASTA	990	113,684
	10 20 30 40 50 60 MTIAESSQKS ATRKPDSMEP ILRLNNIEKS LQDTRDYRGL QLENGLKVLL ISDPNTDVSA 70 80 90 100 110 120 AALSVQVGHM SDPTNLPGLA HFCEHMLFLG TEKYPHENGY TTYLSQSGGS SNAATYPLMT 130 140 150 160 170 180 KYHFHVAPDK LDGALDRFAQ FFIAPLFTPS ATEREINAVN SEHEKNLPSD LWRIKQVNRH 190 200 210 220 230 240 LAKPDHAYSK FGSGNKTTLS EIPKSKNIDV RDELLKFHKQ WYSANIMCLA VIGKESLDEL 250 260 270 280 290 300 EGMVLEKFSE IENKNVKVPG WPRHPYAEER YGQKVKIVPI KDIRSLTISF TTDDLTQFYK 310 320 330 340 350 360 SGPDNYLTHL IGHEGKGSIL SELRRLGWCN DLMAGHQNTQ NGFGFFDIVV DLTQEGLEHV 370 380 390 400 410 420 DDIVKIVFQY LEMLRKEGPK KWIFDECVKL NEMRFRFKEK EQPENLVTHA VSSMQIFPLE 430 440 450 460 470 480 EVLIAPYLSN EWRPDLIKGL LDELVPSKSR IVIVSQSFEP DCDLAEPYYK TKYGITRVAK 490 500 510 520 530 540 DTVQSWENCE LNENLKLALP NSFIPTNFDI SDVPADAPKH PTIILDTPIL RVWHKQDNQF 550 560 570 580 590 600 NKPKACMTFD MSNPIAYLDP LNCNLNHMMV MLLKDQLNEY LYDAELASLK LSVMGKSCGI 610 620 630 640 650 660 DFTIRGFSDK QVVLLEKLLD HLFDFSIDEK RFDILKEEYV RSLKNFKAEQ PYQHSIYYLA 670 680 690 700 710 720 LLLTENAWAN MELLDAMELV TYDRVLNFAK EFFQRLHTEC FIFGNVTKQQ ATDIAGRVNT 730 740 750 760 770 780 RLEATNASKL PILARQMLKK REYKLLAGDS YLFEKENEFH KSSCAQLYLQ CGAQTDHTNI 790 800 810 820 830 840 MVNLVSQVLS EPCYDCLRTK EQLGYIVFSG VRKVNGANGI RIIVQSAKHP SYVEDRIENF 850 860 870 880 890 900 LQTYLQVIED MPLDEFERHK EALAVKKLEK PKTIFQQFSQ FYGEIAMQTY HFEREEAEVA 910 920 930 940 950 960 ILRKISKADF VDYFKKFIAK DGEERRVLSV HIVSQQTDEN ATSEAEPVEI TNMERHKPIS 970 980 990 DIVTFKSCKE LYPIALPFLD IKAKGARSKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of the cDNA for a Drosophila insulin-degrading enzyme." Kuo W.L., Gehm B.D., Rosner M.R. Mol. Endocrinol. 4:1580-1591(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Booth B., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G. , Miranda A., Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E. Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Head.
[5]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 663-990. Strain: Berkeley. Tissue: Embryo.
[6]	"Isolation and characterization of an insulin-degrading enzyme from Drosophila melanogaster." Garcia J.V., Fenton B.W., Rosner M.R. Biochemistry 27:4237-4244(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16, FUNCTION, INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M58465 mRNA. Translation: AAA28439.1. AE014296 Genomic DNA. Translation: AAF51584.3. BT006006 mRNA. Translation: AAO74689.1. Different initiation. BT057994 mRNA. Translation: ACM16704.1. Different initiation. AY061015 mRNA. Translation: AAL28563.1. Different initiation.
PIR	SNFFIN. A37254.
RefSeq	NP_524182.3. NM_079458.4.
UniGene	Dm.7706.
3D structure databases
ProteinModelPortal	P22817.
SMR	P22817. Positions 25-977.
ModBase	Search...
Protein family/group databases
MEROPS	M16.982.
Proteomic databases
PaxDb	P22817.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0273273; FBpp0271781; FBgn0001247.
GeneID	40248.
KEGG	dme:Dmel_CG5517.
Organism-specific databases
CTD	3416.
FlyBase	FBgn0001247. Ide.
Phylogenomic databases
eggNOG	COG1025.
GeneTree	ENSGT00530000063327.
InParanoid	P22817.
KO	K01408.
OMA	FFHELRT.
OrthoDB	EOG4TB2S8.
PhylomeDB	P22817.
Enzyme and pathway databases
SignaLink	P22817.
Gene expression databases
Bgee	P22817.
GermOnline	CG5517. Drosophila melanogaster.
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. drosophila.
GenomeRNAi	40248.
NextBio	817784.

Entry information

Entry name

IDE_DROME

Accession

Primary (citable) accession number: P22817
Secondary accession number(s): B9EQR9 , Q86MR2, Q95S06, Q9VPG8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 106 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project