Search Results

Overview

Uniprot IDP14735
Protein NameInsulin-degrading enzyme
Gene NameIDE
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
697 MTEVAWTKDELKEAL

Function

Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling (PubMed:10684867, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:21098034, PubMed:2293021, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:26968463, PubMed:29596046). Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (PubMed:23922390, PubMed:26394692, PubMed:29596046). Contributes to the regulation of peptide hormone signaling cascades and regulation of blood glucose homeostasis via its role in the degradation of insulin, glucagon and IAPP (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (Probable) (PubMed:26394692, PubMed:9830016). Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (PubMed:21098034). Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (PubMed:21098034). Involved in antigen processing. Produces both the N terminus and the C terminus of MAGEA3-derived antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T lymphocytes by MHC class I

Protein Sequence

10 MRYRLAWLLH 20 PALPSTFRSV 30 LGARLPPPER 40 LCGFQKKTYS 50 KMNNPAIKRI 60 GNHITKSPED 70 KREYRGLELA 80 NGIKVLLISD 90 PTTDKSSAAL 100 DVHIGSLSDP 110 PNIAGLSHFC 120 EHMLFLGTKK 130 YPKENEYSQF 140 LSEHAGSSNA 150 FTSGEHTNYY 160 FDVSHEHLEG 170 ALDRFAQFFL 180 CPLFDESCKD 190 REVNAVDSEH 200 EKNVMNDAWR 210 LFQLEKATGN 220 PKHPFSKFGT 230 GNKYTLETRP 240 NQEGIDVRQE 250 LLKFHSAYYS 260 SNLMAVCVLG 270 RESLDDLTNL 280 VVKLFSEVEN 290 KNVPLPEFPE 300 HPFQEEHLKQ 310 LYKIVPIKDI 320 RNLYVTFPIP 330 DLQKYYKSNP 340 GHYLGHLIGH 350 EGPGSLLSEL 360 KSKGWVNTLV 370 GGQKEGARGF 380 MFFIINVDLT 390 EEGLLHVEDI 400 ILHMFQYIQK 410 LRAEGPQEWV 420 FQECKDLNAV 430 AFRFKDKERP 440 RGYTSKIAGI 450 LHYYPLEEVL 460 TAEYLLEEFR 470 PDLIEMVLDK 480 LRPENVRVAI 490 VSKSFEGKTD 500 RTEEWYGTQY 510 KQEAIPDEVI 520 KKWQNADLNG 530 KFKLPTKNEF 540 IPTNFEILPL 550 EKEATPYPAL 560 IKDTAMSKLW 570 FKQDDKFFLP 580 KACLNFEFFS 590 PFAYVDPLHC 600 NMAYLYLELL 610 KDSLNEYAYA 620 AELAGLSYDL 630 QNTIYGMYLS 640 VKGYNDKQPI 650 LLKKIIEKMA 660 TFEIDEKRFE 670 IIKEAYMRSL 680 NNFRAEQPHQ 690 HAMYYLRLLM 700 TEVAWTKDEL 710 KEALDDVTLP 720 RLKAFIPQLL 730 SRLHIEALLH 740 GNITKQAALG 750 IMQMVEDTLI 760 EHAHTKPLLP 770 SQLVRYREVQ 780 LPDRGWFVYQ 790 QRNEVHNNCG 800 IEIYYQTDMQ 810 STSENMFLEL 820 FCQIISEPCF 830 NTLRTKEQLG 840 YIVFSGPRRA 850 NGIQGLRFII 860 QSEKPPHYLE 870 SRVEAFLITM 880 EKSIEDMTEE 890 AFQKHIQALA 900 IRRLDKPKKL 910 SAECAKYWGE 920 IISQQYNFDR 930 DNTEVAYLKT 940 LTKEDIIKFY 950 KEMLAVDAPR 960 RHKVSVHVLA 970 REMDSCPVVG 980 EFPCQNDINL 990 SQAPALPQPE 1000 VIQNMTEFKR 1010 GLPLFPLVKP HINFMAAKL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016323 basolateral plasma membrane
Cellular Component GO:0009986 cell surface
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0031597 cytosolic proteasome complex
Cellular Component GO:0009897 external side of plasma membrane
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005615 extracellular space
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005782 peroxisomal matrix
Cellular Component GO:0005777 peroxisome
Molecular Function GO:0001540 amyloid-beta binding
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0031626 beta-endorphin binding
Molecular Function GO:0004175 endopeptidase activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0043559 insulin binding
Molecular Function GO:0004222 metalloendopeptidase activity
Molecular Function GO:0042277 peptide binding
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0001618 virus receptor activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0097242 amyloid-beta clearance
Biological Process GO:0150094 amyloid-beta clearance by cellular catabolic process
Biological Process GO:0050435 amyloid-beta metabolic process
Biological Process GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
Biological Process GO:0010815 bradykinin catabolic process
Biological Process GO:0042447 hormone catabolic process
Biological Process GO:1901143 insulin catabolic process
Biological Process GO:1901142 insulin metabolic process
Biological Process GO:0008286 insulin receptor signaling pathway
Biological Process GO:0045861 negative regulation of proteolysis
Biological Process GO:0043171 peptide catabolic process
Biological Process GO:0032092 positive regulation of protein binding
Biological Process GO:0045732 positive regulation of protein catabolic process
Biological Process GO:0030163 protein catabolic process
Biological Process GO:0006508 proteolysis
Biological Process GO:0051603 proteolysis involved in protein catabolic process
Biological Process GO:1903715 regulation of aerobic respiration
Biological Process GO:0010992 ubiquitin recycling

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.