IDE_BOVIN
ID IDE_BOVIN Reviewed; 1019 AA.
AC Q24K02;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Insulin-degrading enzyme;
DE EC=3.4.24.56 {ECO:0000250|UniProtKB:P35559};
DE AltName: Full=Insulin protease;
DE Short=Insulinase;
DE AltName: Full=Insulysin;
GN Name=IDE;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays a role in the cellular breakdown of insulin, APP
CC peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin,
CC kallidin, and other peptides, and thereby plays a role in intercellular
CC peptide signaling (By similarity). Substrate binding induces important
CC conformation changes, making it possible to bind and degrade larger
CC substrates, such as insulin (By similarity). Contributes to the
CC regulation of peptide hormone signaling cascades and regulation of
CC blood glucose homeostasis via its role in the degradation of insulin,
CC glucagon and IAPP. Plays a role in the degradation and clearance of
CC APP-derived amyloidogenic peptides that are secreted by neurons and
CC microglia (By similarity). Degrades the natriuretic peptides ANP, BNP
CC and CNP, inactivating their ability to raise intracellular cGMP (By
CC similarity). Also degrades an aberrant frameshifted 40-residue form of
CC NPPA (fsNPPA) which is associated with familial atrial fibrillation in
CC heterozygous patients (By similarity). Involved in antigen processing.
CC Produces both the N terminus and the C terminus of MAGEA3-derived
CC antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T
CC lymphocytes by MHC class I (By similarity).
CC {ECO:0000250|UniProtKB:P14735, ECO:0000250|UniProtKB:Q9JHR7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Degradation of insulin, glucagon and other polypeptides. No
CC action on proteins.; EC=3.4.24.56;
CC Evidence={ECO:0000250|UniProtKB:P35559};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P35559};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P35559};
CC -!- ACTIVITY REGULATION: Activated by ATP, other nucleotide triphosphates
CC and small peptides. Inhibited by bacitracin.
CC {ECO:0000250|UniProtKB:P35559}.
CC -!- SUBUNIT: Homodimer. Can also form homotetramers.
CC {ECO:0000250|UniProtKB:P35559}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P35559}. Cell membrane
CC {ECO:0000250|UniProtKB:P35559}. Secreted
CC {ECO:0000250|UniProtKB:P35559}.
CC -!- DOMAIN: The SlyX motif may be involved in the non-conventional
CC secretion of the protein. {ECO:0000250|UniProtKB:Q9JHR7}.
CC -!- MISCELLANEOUS: ATP-binding induces a conformation change.
CC {ECO:0000250|UniProtKB:P14735}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
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DR EMBL; BC114105; AAI14106.1; -; mRNA.
DR RefSeq; NP_001069317.1; NM_001075849.1.
DR AlphaFoldDB; Q24K02; -.
DR SMR; Q24K02; -.
DR STRING; 9913.ENSBTAP00000026332; -.
DR MEROPS; M16.002; -.
DR MEROPS; M16.984; -.
DR PaxDb; Q24K02; -.
DR PRIDE; Q24K02; -.
DR Ensembl; ENSBTAT00000026332; ENSBTAP00000026332; ENSBTAG00000019759.
DR GeneID; 523752; -.
DR KEGG; bta:523752; -.
DR CTD; 3416; -.
DR VEuPathDB; HostDB:ENSBTAG00000019759; -.
DR VGNC; VGNC:30033; IDE.
DR eggNOG; KOG0959; Eukaryota.
DR GeneTree; ENSGT00940000155780; -.
DR HOGENOM; CLU_004639_1_1_1; -.
DR InParanoid; Q24K02; -.
DR OMA; WIFDEMK; -.
DR OrthoDB; 1008844at2759; -.
DR TreeFam; TF106275; -.
DR Reactome; R-BTA-5689880; Ub-specific processing proteases.
DR Proteomes; UP000009136; Chromosome 26.
DR Bgee; ENSBTAG00000019759; Expressed in zone of skin and 106 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005782; C:peroxisomal matrix; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0043559; F:insulin binding; IEA:Ensembl.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IEA:Ensembl.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISS:UniProtKB.
DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; ISS:UniProtKB.
DR GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0042447; P:hormone catabolic process; ISS:UniProtKB.
DR GO; GO:1901143; P:insulin catabolic process; ISS:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:1903715; P:regulation of aerobic respiration; IEA:Ensembl.
DR GO; GO:0010992; P:ubiquitin recycling; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Cell membrane; Cytoplasm; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Nucleotide-binding; Protease;
KW Reference proteome; Secreted; Zinc.
FT CHAIN 1..1019
FT /note="Insulin-degrading enzyme"
FT /id="PRO_0000283041"
FT MOTIF 853..858
FT /note="SlyX motif"
FT /evidence="ECO:0000250|UniProtKB:Q9JHR7"
FT ACT_SITE 111
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 359..363
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14735"
FT BINDING 429
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35559"
FT BINDING 895..901
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35559"
FT MOD_RES 192
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHR7"
FT MOD_RES 697
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHR7"
SQ SEQUENCE 1019 AA; 118102 MW; E3B589575B95C861 CRC64;
MRYRLAWLLH SALPSTFRSV LGARLPPSER LCGFQKKTYS KMNNPAIKRI GHHIIKSHED
KREYRGLELA NGIKVLLVSD PTTDKSSAAL DVHIGSLSDP PNIAGLSHFC EHMLFLGTKK
YPKENEYSQF LSEHAGSSNA FTSGEHTNYY FDVSHEHLEG ALDRFAQFFL CPLFDESCKD
REVNAVDSEH EKNVMNDAWR LFQLEKATGN PKHPFSKFGT GNKYTLETRP NQEGIDVRQE
LLKFHSTYYS SNLMAICVLG RESLDDLTNL VVKLFSEVEN KNVPLPEFPE HPFQEEHLKQ
LYKIVPIKDI RNLYVTFPIP DLQKYYKSNP GHYLGHLIGH EGPGSLLSEL KSKGWVNTLV
GGQKEGARGF MFFIINVDLT EEGLLHVEDI ILHMFQYIQK LRAEGPQEWV FQECKDLNAV
AFRFKDKERP RGYTSKIAGI LHYYPLEEVL TAEYLLEEFR PDLIEMVLDK LRPENVRVAI
VSKSFEGKTD RTEEWYGTQY KQEAIPDEVI KKWQNADLNG KFKLPMKNEF IPTNFEILSL
EKEATPYPSL IKDTAMSKLW FKQDDKFFLP KACLNFEFFS PFAYVDPLHC NMAYLYLELL
KDSLNEYAYA AELAGLSYDL QNTIYGMYLS VKGYNDKQPI LLKKIIEKMA TFEIDEKRFE
IIKEAYMRSL NNFRAEQPHQ HAMYYLRLLM TEVAWTKDEL KEALDDVTLP RLKAFIPQLL
SRLHIEALLH GNITKQAALG IMQMVEDTLI EHAHTKPLLP SQLVRYREVQ LPDRGWFVYQ
QRNEVHNNCG IEIYYQTDMQ STSENMFLEL FCQIISEPCF NTLRTKEQLG YIVFSGPRRA
NGIQGLRFII QSEKPPHYLE SRVEAFLITM EKSIEDMTEE AFQKHIQALA IRRLDKPKKL
SAECAKYWGE IISQQYNFDR DNIEVAYLKT LTKEDIIKFY KEMLAVDAPR RHKVSVHVLA
REMDSCPVVG EFPCQNDINL SQAPALPQPE VIQNMTEFKR GLPLFPLVKP HINFMAAKL
