NOS3 and APOE

Data Source:
BioGRID (pull down)

		NOS3	APOE
Description		nitric oxide synthase 3	apolipoprotein E
Image
GO Annotations	Cellular Component	Golgi Membrane Nucleus Cytoplasm Golgi Apparatus Cytosol Cytoskeleton Plasma Membrane Caveola Vesicle Membrane Endocytic Vesicle 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	Actin Monomer Binding Nitric-oxide Synthase Activity Protein Binding Calmodulin Binding FMN Binding Oxidoreductase Activity Oxidoreductase Activity, Acting On Paired Donors, With Incorporation Or Reduction Of Molecular Oxygen, NAD(P)H As One Donor, And Incorporation Of One Atom Of Oxygen Heme Binding Tetrahydrobiopterin Binding Arginine Binding Cadmium Ion Binding Flavin Adenine Dinucleotide Binding NADP 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	Blood Vessel Remodeling Regulation Of Systemic Arterial Blood Pressure By Endothelin Aortic Valve Morphogenesis Pulmonary Valve Morphogenesis Endocardial Cushion Morphogenesis Arginine Catabolic Process Nitric Oxide Biosynthetic Process Mitochondrion Organization Nitric Oxide Mediated Signal Transduction Regulation Of Blood Pressure Negative Regulation Of Cell Population Proliferation Response To Heat Response To Hormone Negative Regulation Of Platelet Activation Positive Regulation Of Gene Expression Negative Regulation Of Muscle Hyperplasia Smooth Muscle Hyperplasia Removal Of Superoxide Radicals Positive Regulation Of Guanylate Cyclase Activity Regulation Of Nervous System Process Response To Lipopolysaccharide Response To Fluid Shear Stress Vasodilation Positive Regulation Of Blood Vessel Endothelial Cell Migration Endothelial Cell Migration Cell Redox Homeostasis Positive Regulation Of Notch Signaling Pathway Positive Regulation Of Angiogenesis Negative Regulation Of Blood Pressure Homeostasis Of Number Of Cells Within A Tissue Regulation Of Nitric-oxide Synthase Activity Negative Regulation Of Biomineral Tissue Development Blood Vessel Diameter Maintenance Negative Regulation Of Extrinsic Apoptotic Signaling Pathway Via Death Domain Receptors	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		ROS and RNS production in phagocytes Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation eNOS activation NOSTRIN mediated eNOS trafficking NOSIP mediated eNOS trafficking Nitric oxide stimulates guanylate cyclase VEGFR2 mediated vascular permeability Extra-nuclear estrogen signaling	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		Arginine Citrulline Sapropterin Miconazole N,N-dimethylarginine L-N(omega)-Nitroarginine-2,4-L-diaminobutyric amide Canavanine 3-Bromo-7-Nitroindazole N-{(4S)-4-Amino-5-[(2-aminoethyl)amino]pentyl}-N'-nitroguanidine N-[3-(aminomethyl)benzyl]acetamidine 1,2,4-Triazole-Carboxamidine L-N(omega)-nitroarginine-(4R)-amino-L-proline amide S,S'-(1,4-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea 7-Nitroindazole S-Ethylisothiourea 2-Aminothiazoline Se-Ethyl-Isoselenourea 2,4-Diamino-6-Phenyl-5,6,7,8,-Tetrahydropteridine N1,N14-Bis((S-Methyl)Isothioureido)Tetradecane Cacodylic acid 7-Nitroindazole-2-Carboxamidine 6-Nitroindazole N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine N(G)-Iminoethylornithine 5,6-Cyclic-Tetrahydropteridine S-Ethyl-N-Phenyl-Isothiourea S,S'-(1,3-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea 6S-5,6,7,8-Tetrahydrobiopterin S-(Dimethylarsenic)Cysteine L-homoarginine S-Isopropyl-Isothiourea Nitroarginine 5-Nitroindazole N-(Chlorophenyl)-N'-hydroxyguanidine (3S,5E)-3-propyl-3,4-dihydrothieno[2,3-f][1,4]oxazepin-5(2H)-imine 5-{4-[(3,5-DIFLUOROBENZYL)AMINO]PHENYL}-6-ETHYLPYRIMIDINE-2,4-DIAMINE ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE N-{(3S,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N'-(4-CHLOROBENZYL)ETHANE-1,2-DIAMINE N-{(3R,4S)-4-[(6-amino-4-methylpyridin-2-yl)methyl]pyrrolidin-3-yl}-N'-(3-chlorobenzyl)ethane-1,2-diamine Levamlodipine	Zinc Copper Zinc acetate Zinc chloride Zinc sulfate, unspecified form
Diseases			Lipoprotein glomerulopathy Hyperlipoproteinemia, type III; Dysbetalipoproteinemia Alzheimer's disease (AD)
GWAS		Coronary artery disease ( 29212778 30104761 26343387) Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease) ( 28714975) Diastolic blood pressure ( 27841878 28739976 27618448) Diastolic blood pressure (cigarette smoking interaction) ( 29455858) Diastolic blood pressure x alcohol consumption interaction (2df test) ( 29912962) Estimated glomerular filtration rate ( 31451708) Eyebrow thickness ( 26926045) Hypertension ( 27618448) Mean arterial pressure ( 27618448) Mean platelet volume ( 32888494) Medication use (agents acting on the renin-angiotensin system) ( 31015401) Medication use (beta blocking agents) ( 31015401) Medication use (calcium channel blockers) ( 31015401) Medication use (diuretics) ( 31015401) Medication use (HMG CoA reductase inhibitors) ( 31015401) Offspring birth weight ( 31043758) Periventricular white matter hyperintensities ( 32517579) Platelet distribution width ( 32888494) Stroke ( 30383316) Systolic blood pressure ( 27841878 27618448 30578418) Systolic blood pressure (cigarette smoking interaction) ( 29455858) Systolic blood pressure x alcohol consumption interaction (2df test) ( 29912962)	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		47 interacting genes: A2M ACTN2 ACTN4 AGTR1 AKT1 APOE APP BDKRB2 BDNF CALM1 CAV1 CDC37 CEP55 EDNRB EFEMP1 EFEMP2 ELAVL1 ELAVL3 EXOC6 EXOSC1 FIS1 GCDH GOLGA2 H3-3A HSP90AA1 HTRA1 IKZF3 IMMT KANK2 MAGEA11 MAST1 MPRIP NMT1 NOSIP NOSTRIN PAXIP1 PI4K2A PPP2R5A PSEN1 PSEN2 RNF31 RNF32 SP1 ST13 TECR TXNDC11 UMPS	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		4846	348
HPRD ID		01224	00135
Ensembl ID		ENSG00000164867	ENSG00000130203
Uniprot IDs		A0S0A6 P29474	A0A0S2Z3D5 P02649
PDB IDs		1M9J 1M9K 1M9M 1M9Q 1M9R 1NIW 2LL7 2MG5 2N8J 3EAH 3NOS 4D1O 4D1P 5UO8 5UO9 5UOA 5UOB 5UOC 5VVB 5VVC 5VVD 5XOF 6AV6 6AV7 6CIE 6CIF 6NH1 6NH2 6NH3 6NH4 6NH5 6NH6 6NH7 6NH8 6NHF 6POU 6POV 6POW 6POX 6POY 6POZ 6PP0 6PP1 6PP2 6PP3 6PP4	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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