PSEN1 and APOE

Data Source:
BioGRID (two hybrid)

		PSEN1	APOE
Description		presenilin 1	apolipoprotein E
Image
GO Annotations	Cellular Component	Golgi Membrane Kinetochore Nucleus Nuclear Outer Membrane Nucleoplasm Mitochondrion Mitochondrial Inner Membrane Lysosomal Membrane Endoplasmic Reticulum Endoplasmic Reticulum Membrane Smooth Endoplasmic Reticulum Rough Endoplasmic Reticulum Golgi Apparatus Centrosome Plasma Membrane Integral Component Of Plasma Membrane Cell Cortex Synaptic Vesicle Cell Surface Membrane Integral Component Of Membrane Aggresome Apical Plasma Membrane Z Disc Cell Junction Growth Cone Neuromuscular Junction Early Endosome Membrane Nuclear Membrane Protein-containing Complex Ciliary Rootlet Azurophil Granule Membrane Sarcolemma Neuron Projection Neuronal Cell Body Dendritic Shaft Membrane Raft Perinuclear Region Of Cytoplasm Gamma-secretase Complex Integral Component Of Presynaptic Membrane	Extracellular Region Extracellular Space Nucleus Cytoplasm Early Endosome Endoplasmic Reticulum Endoplasmic Reticulum Lumen Golgi Apparatus Plasma Membrane Membrane Dendrite Clathrin-coated Endocytic Vesicle Membrane Extracellular Matrix Very-low-density Lipoprotein Particle Low-density Lipoprotein Particle Intermediate-density Lipoprotein Particle High-density Lipoprotein Particle Discoidal High-density Lipoprotein Particle Chylomicron Neuronal Cell Body Synaptic Cleft Collagen-containing Extracellular Matrix Extracellular Exosome Endocytic Vesicle Lumen Blood Microparticle Glutamatergic Synapse Extracellular Vesicle Lipoprotein Particle
	Molecular Function	Endopeptidase Activity Aspartic-type Endopeptidase Activity Calcium Channel Activity Protein Binding Beta-catenin Binding PDZ Domain Binding Aspartic Endopeptidase Activity, Intramembrane Cleaving Cadherin Binding ATPase Binding Growth Factor Receptor Binding	Amyloid-beta Binding Signaling Receptor Binding Structural Molecule Activity Lipid Transporter Activity Protein Binding Phospholipid Binding Heparin Binding Lipid Binding Antioxidant Activity Identical Protein Binding Protein Homodimerization Activity Heparan Sulfate Proteoglycan Binding Protein-containing Complex Binding Metal Chelating Activity Protein Dimerization Activity Tau Protein Binding Low-density Lipoprotein Particle Receptor Binding Phosphatidylcholine-sterol O-acyltransferase Activator Activity Very-low-density Lipoprotein Particle Receptor Binding Lipoprotein Particle Binding Cholesterol Transfer Activity
	Biological Process	Autophagosome Assembly Negative Regulation Of Transcription By RNA Polymerase II Activation Of MAPKK Activity Blood Vessel Development Cell Fate Specification Somitogenesis Neuron Migration Positive Regulation Of Receptor Recycling Heart Looping Positive Regulation Of L-glutamate Import Across Plasma Membrane Hematopoietic Progenitor Cell Differentiation Astrocyte Activation Involved In Immune Response T Cell Activation Involved In Immune Response Neural Retina Development Protein Glycosylation Membrane Protein Ectodomain Proteolysis Calcium Ion Transport Mitochondrial Transport Cellular Response To DNA Damage Stimulus Response To Oxidative Stress Negative Regulation Of Epidermal Growth Factor-activated Receptor Activity Notch Receptor Processing Learning Or Memory Memory Post-embryonic Development Regulation Of Gene Expression Positive Regulation Of Gene Expression Negative Regulation Of Gene Expression Regulation Of Neuron Projection Development Protein Transport Choline Transport Synaptic Vesicle Targeting Protein Processing Cerebellum Development Cerebral Cortex Cell Migration Cajal-Retzius Cell Differentiation Dorsal/ventral Neural Tube Patterning Embryonic Limb Morphogenesis Membrane Protein Intracellular Domain Proteolysis Positive Regulation Of Protein Binding Positive Regulation Of Proteasomal Ubiquitin-dependent Protein Catabolic Process Endoplasmic Reticulum Calcium Ion Homeostasis Positive Regulation Of Tumor Necrosis Factor Production Amyloid-beta Formation Notch Receptor Processing, Ligand-dependent Intracellular Signal Transduction Positive Regulation Of Protein Import Into Nucleus Regulation Of Phosphorylation Positive Regulation Of Phosphorylation Amyloid Precursor Protein Metabolic Process Amyloid Precursor Protein Catabolic Process Myeloid Dendritic Cell Differentiation Positive Regulation Of Apoptotic Process Negative Regulation Of Apoptotic Process Positive Regulation Of Catalytic Activity Neutrophil Degranulation Positive Regulation Of MAP Kinase Activity Negative Regulation Of Neuron Apoptotic Process Skin Morphogenesis Positive Regulation Of Glycolytic Process Positive Regulation Of Transcription, DNA-templated Ephrin Receptor Signaling Pathway Astrocyte Activation Regulation Of Synaptic Plasticity Thymus Development Neuron Development Skeletal System Morphogenesis Brain Morphogenesis Amyloid-beta Metabolic Process Epithelial Cell Proliferation Negative Regulation Of Axonogenesis Synapse Organization Positive Regulation Of Coagulation T Cell Receptor Signaling Pathway Sequestering Of Calcium Ion Neuron Apoptotic Process Negative Regulation Of Ubiquitin-protein Transferase Activity Smooth Endoplasmic Reticulum Calcium Ion Homeostasis Regulation Of Synaptic Transmission, Glutamatergic Regulation Of Resting Membrane Potential Regulation Of Canonical Wnt Signaling Pathway Positive Regulation Of Dendritic Spine Development Calcium Ion Transmembrane Transport Modulation Of Age-related Behavioral Decline Cell-cell Adhesion L-glutamate Import Across Plasma Membrane Cellular Response To Amyloid-beta Negative Regulation Of Core Promoter Binding Negative Regulation Of Low-density Lipoprotein Receptor Activity Positive Regulation Of Amyloid Fibril Formation Neuron Projection Maintenance Negative Regulation Of Ubiquitin-dependent Protein Catabolic Process Negative Regulation Of Apoptotic Signaling Pathway	Response To Reactive Oxygen Species Retinoid Metabolic Process Negative Regulation Of Endothelial Cell Proliferation Response To Dietary Excess Regulation Of Transcription By RNA Polymerase II Triglyceride Metabolic Process Cholesterol Catabolic Process Cellular Calcium Ion Homeostasis Receptor-mediated Endocytosis Cytoskeleton Organization G Protein-coupled Receptor Signaling Pathway Nitric Oxide Mediated Signal Transduction Synaptic Transmission, Cholinergic Long-term Memory Cholesterol Metabolic Process Gene Expression Negative Regulation Of Platelet Activation Negative Regulation Of Endothelial Cell Migration Negative Regulation Of Gene Expression Positive Regulation Of Cholesterol Esterification Positive Regulation Of Cholesterol Efflux Lipid Transport Involved In Lipid Storage Positive Regulation Of Neuron Projection Development Negative Regulation Of Neuron Projection Development Long-chain Fatty Acid Transport Protein Import Virion Assembly CGMP-mediated Signaling Negative Regulation Of Blood Coagulation Regulation Of Axon Extension Neuron Projection Development Negative Regulation Of Cellular Protein Metabolic Process Regulation Of Cdc42 Protein Signal Transduction Positive Regulation Of Low-density Lipoprotein Particle Receptor Catabolic Process Cholesterol Efflux Phospholipid Efflux Chylomicron Remodeling Very-low-density Lipoprotein Particle Remodeling Low-density Lipoprotein Particle Remodeling High-density Lipoprotein Particle Remodeling Chylomicron Assembly High-density Lipoprotein Particle Assembly Chylomicron Remnant Clearance High-density Lipoprotein Particle Clearance Very-low-density Lipoprotein Particle Clearance Locomotory Exploration Behavior Lipoprotein Biosynthetic Process Lipoprotein Catabolic Process Vasodilation Cholesterol Homeostasis Amyloid Precursor Protein Metabolic Process Regulation Of Protein-containing Complex Assembly Negative Regulation Of MAP Kinase Activity Negative Regulation Of Neuron Apoptotic Process Negative Regulation Of Blood Vessel Endothelial Cell Migration Post-translational Protein Modification Reverse Cholesterol Transport Cellular Protein Metabolic Process Positive Regulation By Host Of Viral Process Regulation Of Innate Immune Response Negative Regulation Of Cholesterol Biosynthetic Process Positive Regulation Of Endocytosis Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Lipid Biosynthetic Process Intracellular Transport Regulation Of Neuronal Synaptic Plasticity Artery Morphogenesis Negative Regulation Of Protein Secretion Negative Regulation Of Inflammatory Response Positive Regulation Of Nitric-oxide Synthase Activity Positive Regulation Of Membrane Protein Ectodomain Proteolysis Regulation Of Protein Metabolic Process Maintenance Of Location In Cell Fatty Acid Homeostasis Positive Regulation Of Dendritic Spine Development Regulation Of Proteasomal Protein Catabolic Process Response To Caloric Restriction Triglyceride Homeostasis Positive Regulation Of ERK1 And ERK2 Cascade Triglyceride-rich Lipoprotein Particle Clearance Intermediate-density Lipoprotein Particle Clearance Negative Regulation Of Canonical Wnt Signaling Pathway Regulation Of Cholesterol Metabolic Process Negative Regulation Of Triglyceride Metabolic Process AMPA Glutamate Receptor Clustering NMDA Glutamate Receptor Clustering Cellular Oxidant Detoxification Intermembrane Lipid Transfer Regulation Of Amyloid-beta Clearance Positive Regulation Of Amyloid-beta Clearance Negative Regulation Of Long-term Synaptic Potentiation Negative Regulation Of Amyloid-beta Formation Positive Regulation Of Dendritic Spine Maintenance Regulation Of Amyloid Precursor Protein Catabolic Process Positive Regulation Of Phospholipid Efflux Positive Regulation Of Lipid Transport Across Blood-brain Barrier Positive Regulation Of Heparan Sulfate Binding Positive Regulation Of Heparan Sulfate Proteoglycan Binding Regulation Of Cellular Response To Very-low-density Lipoprotein Particle Stimulus Regulation Of Amyloid Fibril Formation Negative Regulation Of Amyloid Fibril Formation Positive Regulation Of Amyloid Fibril Formation Regulation Of Behavioral Fear Response
Pathways		Nuclear signaling by ERBB4 Degradation of the extracellular matrix Regulated proteolysis of p75NTR NRIF signals cell death from the nucleus Activated NOTCH1 Transmits Signal to the Nucleus Constitutive Signaling by NOTCH1 PEST Domain Mutants Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants NOTCH2 Activation and Transmission of Signal to the Nucleus EPH-ephrin mediated repulsion of cells Neutrophil degranulation NOTCH3 Activation and Transmission of Signal to the Nucleus NOTCH4 Activation and Transmission of Signal to the Nucleus Noncanonical activation of NOTCH3	Nuclear signaling by ERBB4 Scavenging by Class A Receptors Scavenging by Class A Receptors Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors Post-translational protein phosphorylation Chylomicron assembly Chylomicron remodeling Chylomicron clearance Chylomicron clearance HDL remodeling NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux Retinoid metabolism and transport Retinoid metabolism and transport
Drugs			Zinc Copper Zinc acetate Zinc chloride Zinc sulfate, unspecified form
Diseases		Acne inversa; Hidradenitis supprativa Frontotemporal lobar degeneration (FTLD), including: Pick disease of brain; Frontotemporal dementia (FTD); Ubiquitin-positive frontotemporal dementia (UP-FTD); Progressive supranuclear palsy type 1 (PSNP1); Inclusion body myopathy with early-onset paget disease and frontotemporal dementia (IBMPFD); Frontotemporal dementia, chromosome 3-linked (FTD3) Alzheimer's disease (AD)	Lipoprotein glomerulopathy Hyperlipoproteinemia, type III; Dysbetalipoproteinemia Alzheimer's disease (AD)
GWAS		Apolipoprotein B levels ( 32203549) Red cell distribution width ( 32888494) Refractive error ( 32231278) Reticulocyte fraction of red cells ( 32888494)	Adult body size ( 32376654) Advanced age-related macular degeneration ( 26691988) Age-related cognitive decline (memory) (slope of z-scores) ( 30954325) Age-related macular degeneration ( 23326517 23455636) Alzheimer disease and age of onset ( 26830138) Alzheimer's disease ( 17975299 22832961 24770881 20460622 30636644 17998437 18823527 19734902 19734903 21627779 24755620 19125160 20061627 22245343 31473137) Alzheimer's disease (age of onset) ( 22005931) Alzheimer's disease (late onset) ( 17474819 20885792 23565137 26339675 30617256 28714976) Alzheimer's disease (onset at age over 80) ( 30979435) Alzheimer's disease (onset between ages 58 and 79) ( 30979435) Alzheimer's disease biomarkers ( 23562540 21123754 23419831) Alzheimer's disease in hypertension ( 31055733) Alzheimer's disease in hypertension-negative individuals ( 31055733) Alzheimer's disease or family history of Alzheimer's disease ( 30617256) Alzheimer's disease or HDL levels (pleiotropy) ( 30805717) Alzheimer's disease progression score ( 29860282) Alzheimerâ€™s disease (clinical subgroup AD+) ( 31473137) Alzheimerâ€™s disease (clinical subgroup AD++) ( 31473137) Alzheimerâ€™s disease (clinical subgroup AD+++) ( 31473137) Alzheimerâ€™s disease and/or vascular dementia (clinical subgroup VaD+) ( 31473137) Apolipoprotein A1 levels ( 32203549) Apolipoprotein Levels ( 23031429) Blood metabolite ratios ( 24816252) Blood protein levels ( 29875488) Body fat percentage ( 26833246) Body mass index ( 26426971) Body mass index (age>50) ( 26426971) Body mass index x age interaction ( 26426971) Body mass index x sex x age interaction (4df test) ( 26426971) Brain imaging ( 20100581) C-reactive protein ( 19567438 18439548 18439552 23844046) C-reactive protein levels ( 29403010 30388399) Cardiovascular risk factors ( 20838585) Carotid intima media thickness ( 30510157) Carotid intima media thickness (maximum) ( 31801372) Carotid intima media thickness (mean) ( 31801372) Cerebral amyloid deposition (PET imaging) ( 26252872 30361487) Cerebral amyloid deposition positivity (PET imaging) ( 26252872) Cerebrospinal AB1-42 levels in Alzheimer's disease dementia ( 29274321 25027320) Cerebrospinal AB1-42 levels in mild cognitive impairment ( 29274321) Cerebrospinal AB1-42 levels in normal cognition ( 29274321) Cerebrospinal fluid AB1-42 levels ( 28247064 30319691 28641921 29274321) Cerebrospinal fluid p-tau levels ( 29274321) Cerebrospinal fluid p-tau levels in mild cognitive impairment ( 29274321) Cerebrospinal fluid p-Tau181p:AB1-42 ratio ( 30319691) Cerebrospinal fluid t-tau levels ( 28641921 29274321) Cerebrospinal fluid t-tau levels in mild cognitive impairment ( 29274321) Cerebrospinal fluid t-tau:AB1-42 ratio ( 30319691 28641921) Cerebrospinal P-tau181p levels ( 28247064) Cerebrospinal T-tau levels ( 28247064) Cholesterol, total ( 24097068 28270201 19060911 25961943 20686565) Cingulate cortical amyloid beta load ( 26421299) Cognitive decline ( 22054870) Cognitive decline (age-related) ( 28078323 24468470) Cognitive impairment test score ( 30319691) Coronary artery disease ( 32469254 29212778 30104761 26343387) Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease) ( 28714975) Dementia with Lewy bodies ( 29263008 31065058) Family history of Alzheimer's disease ( 30617256) Fasting triglyceride levels ( 32603185) Fish- and plant-related diet ( 32066663) Free cholesterol levels in large LDL ( 29084231) Fruit consumption ( 32066663) Gut microbiota (functional units) ( 27694959) HDL cholesterol ( 24097068 21909109 28270201 19060911 30275531 25961943 20686565) HDL cholesterol levels ( 32203549 28334899 26690388) High density lipoprotein cholesterol levels ( 29403010) High light scatter reticulocyte count ( 27863252) High light scatter reticulocyte percentage of red cells ( 27863252) Hippocampal atrophy ( 22745009) Hippocampal volume ( 29274321) Hippocampal volume in Alzheimer's disease dementia ( 29274321) Ideal cardiovascular health (clinical) ( 27179730) Immature fraction of reticulocytes ( 27863252) Lamb consumption ( 32066663) Late-onset Alzheimer's disease ( 29360470) LDL cholesterol ( 23726366 24097068 18802019 24507774 18193043 18193044 20864672 26160806 19060906 19060911 25961943 23067351 20686565) LDL cholesterol levels ( 28334899 31087446 26763881 28371326 17463246) LDL cholesterol levels x long total sleep time interaction (2df test) ( 31719535) LDL cholesterol levels x short total sleep time interaction (2df test) ( 31719535) Lewy body disease ( 25188341) Lipid metabolism phenotypes ( 22286219) Lipid or lipoprotein levels ( 23696881) Lipid traits ( 30576415 24023260) Lipoprotein (a) levels ( 28512139) Lipoprotein phospholipase A2 activity in cardiovascular disease ( 28753643) Lipoprotein(a) levels adjusted for apolipoprotein(a) isoforms ( 28512139) Lipoprotein-associated phospholipase A2 activity and mass ( 23118302) Lipoprotein-associated phospholipase A2 activity change in response to darapladib treatment in cardiovascular disease ( 28753643) Liver fat content (MRI proton density fat fraction measure) ( 32247823) Lobar intracerebral hemorrhage ( 31430377) Logical memory (delayed recall) ( 29274321) Logical memory (immediate recall) ( 29274321) Longevity ( 21418511 31484785) Longevity (85 years and older) ( 24688116) Longevity (90 years and older) ( 24688116) Longevity (age >90th survival percentile) ( 31413261) Longevity (age >99th survival percentile) ( 31413261) Low density lipoprotein cholesterol levels ( 30718733 29403010 31969989 28548082) Low density lipoprotein cholesterol levels (on statin treatment) ( 31969989) Mean reticulocyte volume ( 32888494) Mean spheric corpuscular volume ( 32888494) Meat-related diet ( 32066663) Medication use (agents acting on the renin-angiotensin system) ( 31015401) Medication use (antithrombotic agents) ( 31015401) Medication use (calcium channel blockers) ( 31015401) Medication use (HMG CoA reductase inhibitors) ( 31015401) Medication use (salicylic acid and derivatives) ( 31015401) Mental health study participation (completed survey) ( 31263887) Metabolic syndrome ( 22399527) Metabolite levels ( 22916037) Metabolite levels (lipoprotein measures) ( 27005778) Moderate to vigorous physical activity levels ( 29899525) Mortality ( 27029810) Neuritic plaque ( 31497858) Neuritic plaques or cerebral amyloid angiopathy (pleiotropy) ( 29458411) Neuritic plaques or neurofibrillary tangles (pleiotropy) ( 29458411) Neurofibrillary tangles ( 31497858) Neurofibrillary tangles or cerebral amyloid angiopathy (pleiotropy) ( 29458411) Parental lifespan ( 30642433 29030599) Parental longevity (both parents in top 10%) ( 29227965) Parental longevity (combined parental age at death) ( 29227965) Parental longevity (combined parental attained age, Martingale residuals) ( 29227965) Parental longevity (father's age at death) ( 29227965) Parental longevity (father's attained age) ( 29227965) Parental longevity (mother's age at death or mother's attained age) ( 31484785) Parental longevity (mother's age at death) ( 31484785 29227965) Parental longevity (mother's attained age) ( 29227965) Parkinson's disease (age of onset) ( 30957308) Parkinson's disease progression (cognitive) ( 33111402) Parkinson's disease progression (composite) ( 33111402) Platelet count ( 32888494 27863252) Plateletcrit ( 32888494) Posterior cortical atrophy and Alzheimer's disease ( 26993346) Postprandial triglyceride levels ( 32603185) Psychosis and Alzheimer's disease ( 22005930) Pulse pressure ( 30224653 30578418) Quantitative traits ( 19197348) Red cell distribution width ( 32888494 27863252 28957414) Refractive error ( 32231278) Relative sugar intake ( 32393786) Response to statins (LDL cholesterol change) ( 25350695 22331829 31969989) Response to statins (LDL cholesterol percent change) ( 31969989) Resting heart rate ( 27798624) Reticulocyte count ( 32888494 27863252) Reticulocyte fraction of red cells ( 32888494 27863252) Serum metabolite levels ( 31636271) Serum metabolite levels (CMS) ( 31636271) Serum total cholesterol levels ( 29084231) Sphingolipid levels ( 26068415) Systolic blood pressure ( 30578418) Total cholesterol levels ( 30718733 28334899 26690388 31087446 29403010 28548082) Total cholesterol levels in LDL ( 29084231) Triglyceride levels ( 30718733 28334899 29403010) Triglycerides ( 24507774 19060911 25961943 20686565 26582766) Type 2 diabetes ( 27189021 30297969 28869590) Verbal declarative memory ( 25648963) Verbal memory performance (immediate recall change) ( 28800603) Verbal memory performance (residualized delayed recall level) ( 28800603) Very long-chain saturated fatty acid levels (fatty acid 20:0) ( 25378659) Vigorous physical activity ( 29899525) White matter hyperintensities ( 32358547)
Interacting Genes		92 interacting genes: ACTN1 AP1M2 APBA1 APH1A APH1B APOE APP BACE1 BCL2 BCL2L1 CASP1 CASP3 CASP4 CASP6 CASP7 CASP8 CDH1 CDK5 CFL1 CIB1 CTNNA1 CTNNB1 CTNND1 CTNND2 CYP2C18 CYP2C8 DLL1 DOCK3 ECSIT EFHD1 EFNB2 ENSA EPB41L3 ERN1 ETFA FBXL12 FBXW7 FGF13 FLNA FLNB GAPDH GCDH GDI1 GFAP GSK3B HERPUD1 HMGB1 ICAM5 ITSN2 JUP KANK2 KCNIP3 KCNIP4 MAPK9 MAPT METTL2B MTCH1 NCSTN NOS3 NOTCH1 NOTCH2 NOTCH3 NOTCH4 OXCT1 PDCD4 PIK3R1 PKP4 PRAM1 PRDX2 PRKACA PRKCZ PSENEN PSMA5 PSMB1 RAB11A RAB3A RAD23A RHEB RMDN3 RNF32 RYR2 SCAF11 SCN1A SLC10A6 ST13 STAMBPL1 TCF7L2 TDP2 TUBA1B UBQLN1 UMPS YME1L1	56 interacting genes: A2M ALB ANKH APP ARFGAP1 CDC37 CNTF CSNK2A1 CTSB CYP2C18 CYP2C8 ECSIT ELAVL1 EPN2 FARSA FBXL12 FOXG1 FXYD7 GCDH HTRA1 IFIT3 IFIT5 IQSEC1 LCAT LDLR LINC02582 LONP1 LOXL4 LRP1 LRP2 LRP8 MAP2 MAPT MAST1 MID1IP1 NEFM NOS3 PCMT1 PDCD4 PLEKHA6 PLTP PRAM1 PRDX2 PRNP PSEN1 RHEB RNF32 RPL4 SCARB1 SORL1 ST13 TIMM29 TREM2 TYRO3 VLDLR ZNF558
Entrez ID		5663	348
HPRD ID		00087	00135
Ensembl ID		ENSG00000080815	ENSG00000130203
Uniprot IDs		A0A024R6A3 A0A0S2Z4D2 P49768	A0A0S2Z3D5 P02649
PDB IDs		2KR6 4UIS 5A63 5FN2 5FN3 5FN4 5FN5 6IDF 6IYC	1B68 1BZ4 1EA8 1GS9 1H7I 1LE2 1LE4 1LPE 1NFN 1NFO 1OEF 1OEG 1OR2 1OR3 2KC3 2KNY 2L7B 6IWB 6NCN 6NCO
Enriched GO Terms of Interacting Partners?
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