MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
1.14.13.39	Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor; nitric-oxide synthase (NADPH)

Structure

PDB	Resolution (Å)	PDB name
1M9J	2.43	human endothelial nitric oxide synthase with chlorzoxazone bound
1M9K	2.01	Human Endothelial Nitric Oxide Synthase with 7-Nitroindazole Bound
1M9M	1.96	human endothelial nitric oxide synthase with 6-nitroindazole bound
1M9Q	2.01	human endothelial nitric oxide synthase with 5-nitroindazole bound
1M9R	2.56	human endothelial nitric oxide synthase with 3-Bromo-7-Nitroindazole bound
1NIW	2.05	Crystal structure of endothelial nitric oxide synthase peptide bound to calmodulin
2LL7		Solution NMR structure of CaM bound to the eNOS CaM binding domain peptide
2MG5		Solution Structure of Calmodulin bound to the target peptide of Endothelial Nitrogen Oxide Synthase phosphorylated at Thr495
2N8J		Structure and 15N relaxation data of Calmodulin bound to the endothelial Nitric Oxide Synthase Calmodulin Binding Domain Peptide at Physiological Calcium Concentration
3EAH	2.44	Structure of inhibited human eNOS oxygenase domain
3NOS	2.4	HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE
4D1O	1.819	Structure of human endothelial nitric oxide synthase heme domain with L-Arg bound
4D1P	1.731	Structure of human endothelial nitric oxide synthase heme domain IN COMPLEX WITH 6-((((3S, 5R)-5-(((6-AMINO-4-METHYLPYRIDIN-2-YL)METHOXY) METHYL)PYRROLIDIN-3-YL)OXY) METHYL)-4-METHYLPYRIDIN-2-AMINE
5UO8	2.18	Structure of human endothelial nitric oxide synthase heme domain in complex with 3-[(2-aminoquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile
5UO9	2.19	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-[(3-Ethyl-5-((methylamino)methyl)phenoxy)methyl]quinolin-2-amine
5UOA	2.2	Structure of human endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile
5UOB	2.292	Structure of human endothelial nitric oxide synthase heme domain in complex with (R)-3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)propyl)benzonitrile
5UOC	2.2	Structure of human endothelial nitric oxide synthase heme domain in complex with (S)-3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)propyl)benzonitrile
5VVB	2.15	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Aminoquinolin-7-yl)methyl)amino)ethyl)-2-methylbenzonitrile
5VVC	2.4	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)-2-methylbenzonitrile
5VVD	2.25	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile
5XOF	1.963	Crystal structure of human paired immunoglobulin-like type 2 receptor alpha with synthesized glycopeptide I
6AV6	2.08	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-Fluoro-5-(3-(methylamino)propyl)phenethyl)-4-methylpyridin-2-amine
6AV7	1.916	Structure of human endothelial nitric oxide synthase heme domain in complex with HW69
6CIE	1.95	Structure of human endothelial nitric oxide synthase heme domain in complex with N-(1-(2-(Ethyl(methyl)amino)ethyl)-1,2,3,4-tetrahydroquino-lin-6-yl)thiophene-2-carboximidamide
6CIF	2.2	Structure of the human endothelial nitric oxide synthase heme domain in complex with N-(1-(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide
6NH1	2.216	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-fluoro-5-(3-(methylamino)prop-1-yn-1-yl)phenethyl)-4-methylpyridin-2-amine
6NH2	2.29	Structure of human endothelial nitric oxide synthase heme domain in complex with (R)-6-(3-fluoro-5-(2-(pyrrolidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
6NH3	2.01	Structure of human endothelial nitric oxide synthase heme domain in complex with (S)-6-(3-fluoro-5-(2-(pyrrolidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
6NH4	2.27	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-fluoro-5-(2-((2R,4S)-4-fluoropyrrolidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
6NH5	1.959	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-fluoro-5-(2-((2R,4S)-4-fluoro-1-methylpyrrolidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
6NH6	2.189	Structure of the human endothelial nitric oxide synthase heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-2,6-difluorophenethyl)-4-methylpyridin-2-amine
6NH7	1.9	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-2,5,6-trifluorophenethyl)-4-methylpyridin-2-amine
6NH8	1.8	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(5-(3-(dimethylamino)propyl)-2,3,4-trifluorophenethyl)-4-methylpyridin-2-amine
6NHF	1.83	Structure of human endothelial nitric oxide synthase heme domain in complex with (S)-6-(2,3-difluoro-5-(2-(1-methylazetidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
6POU	2.194	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(4-(2-Aminoethyl)phenyl)-4-methylquinolin-2-amine
6POV	2.047	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(2-Aminoethyl)phenyl)-4-methylquinolin-2-amine
6POW	2.15	Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine
6POX	2.197	Structure of human endothelialnitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-ethoxyphenyl)-4-methylquinolin-2-amine
6POY	2.3	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-propoxyphenyl)-4-methylquinolin-2-amine
6POZ	2.2	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-isopropoxyphenyl)-4-methylquinolin-2-amine
6PP0	1.97	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-(cyclobutylmethoxy)phenyl)-4-methylquinolin-2-amine
6PP1	1.76	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-(cyclopropylmethoxy)phenyl)-4-methylquinolin-2-amine
6PP2	2.02	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-((4-(2-Amino-4-methylquinolin-7-yl)-2-(aminomethyl)phenoxy)methyl)benzonitrile
6PP3	1.95	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-(pyridin-2-ylmethoxy)phenyl)-4-methylquinolin-2-amine
6PP4	2.2	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-(pyridin-3-ylmethoxy)phenyl)-4-methylquinolin-2-amine
7M56	1.957	Structure of human endothelial nitric oxide synthase heme domain in complex with 7-((3-(3-aminophenethyl)phenoxy)methyl)quinolin-2-amine
7TSG	1.85	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(dimethylamino)propyl)-4-methylpyridin-2-amine
7TSH	2.145	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-methyl-6-(3-(methylamino)propyl)pyridin-2-amine
7TSI	2.1	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-methyl-6-(3-((methylamino)methyl)phenyl)pyridin-2-amine
7TSK	2.049	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-methyl-6-(3-(methylamino)prop-1-yn-1-yl)pyridin-2-amine
7TSL	1.9	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-methyl-6-(3-(4-methylpiperazin-1-yl)propyl)pyridin-2-amine
7TSM	1.85	Structure of human endothelial nitric oxide synthase heme domain in complex with 4-methyl-6-(3-(4-methylpiperazin-1-yl)prop-1-yn-1-yl)pyridin-2-amine bishydrochloride
7TSN	2.08	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(3,3-difluoroazetidin-1-yl)prop-1-yn-1-yl)-4-methylpyridin-2-amine
7TSO	2.0	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(3,3-difluoroazetidin-1-yl)propyl)-4-methylpyridin-2-amine
7TSP	2.0	Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(4,4-difluoropiperidin-1-yl)prop-1-yn-1-yl)-4-methylpyridin-2-amine
7UAO	1.9	Structure of human endothelial nitric oxide synthase heme domain in complex with (6-(3-(4,4-difluoropiperidin-1-yl)propyl)-4-methylpyridin-2-amine)

GO term

GO ontology	GO term	GO description
Biological Process	GO:0001525	angiogenesis
Biological Process	GO:0003180	aortic valve morphogenesis
Biological Process	GO:0006527	arginine catabolic process
Biological Process	GO:0097746	blood vessel diameter maintenance
Biological Process	GO:0001974	blood vessel remodeling
Biological Process	GO:0006816	calcium ion transport
Biological Process	GO:0045454	cell redox homeostasis
Biological Process	GO:0003203	endocardial cushion morphogenesis
Biological Process	GO:0043542	endothelial cell migration
Biological Process	GO:0051649	establishment of localization in cell
Biological Process	GO:0048873	homeostasis of number of cells within a tissue
Biological Process	GO:0001701	in utero embryonic development
Biological Process	GO:0031663	lipopolysaccharide-mediated signaling pathway
Biological Process	GO:0030324	lung development
Biological Process	GO:0007005	mitochondrion organization
Biological Process	GO:0070168	negative regulation of biomineral tissue development
Biological Process	GO:0045776	negative regulation of blood pressure
Biological Process	GO:0051926	negative regulation of calcium ion transport
Biological Process	GO:0008285	negative regulation of cell population proliferation
Biological Process	GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Biological Process	GO:0051346	negative regulation of hydrolase activity
Biological Process	GO:0014740	negative regulation of muscle hyperplasia
Biological Process	GO:0010544	negative regulation of platelet activation
Biological Process	GO:0043267	negative regulation of potassium ion transport
Biological Process	GO:0048662	negative regulation of smooth muscle cell proliferation
Biological Process	GO:0006809	nitric oxide biosynthetic process
Biological Process	GO:0007263	nitric oxide mediated signal transduction
Biological Process	GO:0001542	ovulation from ovarian follicle
Biological Process	GO:0045747	positive regulation of Notch signaling pathway
Biological Process	GO:0045766	positive regulation of angiogenesis
Biological Process	GO:0043536	positive regulation of blood vessel endothelial cell migration
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:0031284	positive regulation of guanylate cyclase activity
Biological Process	GO:0006813	potassium ion transport
Biological Process	GO:0003184	pulmonary valve morphogenesis
Biological Process	GO:0008217	regulation of blood pressure
Biological Process	GO:0031644	regulation of nervous system process
Biological Process	GO:0002028	regulation of sodium ion transport
Biological Process	GO:0003100	regulation of systemic arterial blood pressure by endothelin
Biological Process	GO:0003057	regulation of the force of heart contraction by chemical signal
Biological Process	GO:0019430	removal of superoxide radicals
Biological Process	GO:0034405	response to fluid shear stress
Biological Process	GO:0009408	response to heat
Biological Process	GO:0009725	response to hormone
Biological Process	GO:0032496	response to lipopolysaccharide
Biological Process	GO:0014806	smooth muscle hyperplasia
Biological Process	GO:0042311	vasodilation
Biological Process	GO:0060412	ventricular septum morphogenesis
Molecular Function	GO:0010181	FMN binding
Molecular Function	GO:0050661	NADP binding
Molecular Function	GO:0003785	actin monomer binding
Molecular Function	GO:0034618	arginine binding
Molecular Function	GO:0046870	cadmium ion binding
Molecular Function	GO:0005516	calmodulin binding
Molecular Function	GO:0050660	flavin adenine dinucleotide binding
Molecular Function	GO:0020037	heme binding
Molecular Function	GO:0004517	nitric-oxide synthase activity
Molecular Function	GO:0097110	scaffold protein binding
Molecular Function	GO:0034617	tetrahydrobiopterin binding
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0000139	Golgi membrane
Cellular Component	GO:0005901	caveola
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005856	cytoskeleton
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030666	endocytic vesicle membrane
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0012506	vesicle membrane

InterPro / Pfam

InterPro	InterPro name
IPR001094	Flavodoxin-like
IPR001433	Oxidoreductase FAD/NAD(P)-binding
IPR001709	Flavoprotein pyridine nucleotide cytochrome reductase
IPR003097	Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding
IPR004030	Nitric oxide synthase, N-terminal
IPR008254	Flavodoxin/nitric oxide synthase
IPR012144	Nitric-oxide synthase, eukaryote
IPR017927	FAD-binding domain, ferredoxin reductase-type
IPR017938	Riboflavin synthase-like beta-barrel
IPR023173	NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily
IPR029039	Flavoprotein-like superfamily
IPR036119	Nitric oxide synthase, N-terminal domain superfamily
IPR039261	Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
IPR044940	Nitric oxide synthase, domain 2 superfamily
IPR044943	Nitric oxide synthase, domain 1 superfamily
IPR044944	Nitric oxide synthase, domain 3 superfamily

Pfam	Pfam name
PF00175	Oxidoreductase NAD-binding domain
PF00258	Flavodoxin
PF00667	FAD binding domain
PF02898	Nitric oxide synthase, oxygenase domain

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-1222556	ROS and RNS production in phagocytes	Internal node	R-HSA-168256	Immune System
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	Leaf	R-HSA-1430728	Metabolism
R-HSA-203615	eNOS activation	Leaf	R-HSA-1430728	Metabolism
R-HSA-203641	NOSTRIN mediated eNOS trafficking	Leaf	R-HSA-1430728	Metabolism
R-HSA-203754	NOSIP mediated eNOS trafficking	Leaf	R-HSA-1430728	Metabolism
R-HSA-392154	Nitric oxide stimulates guanylate cyclase	Internal node	R-HSA-109582	Hemostasis
R-HSA-5218920	VEGFR2 mediated vascular permeability	Leaf	R-HSA-162582	Signal Transduction
R-HSA-9009391	Extra-nuclear estrogen signaling	Internal node	R-HSA-162582	Signal Transduction

Location	ECO term	Pubmed
Cell membrane
Cytoplasm, cytoskeleton
Golgi apparatus
Membrane, caveola

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000093	Proteinuria
HP:0000726	Dementia
HP:0000822	Hypertension
HP:0000969	Edema
HP:0001250	Seizure
HP:0001297	Stroke
HP:0001300	Parkinsonism
HP:0001426	Multifactorial inheritance
HP:0001511	Intrauterine growth retardation
HP:0001873	Thrombocytopenia
HP:0002185	Neurofibrillary tangles
HP:0002423	Long-tract signs
HP:0002511	Alzheimer disease
HP:0002910	Elevated hepatic transaminase
HP:0003581	Adult onset
HP:0004421	Elevated systolic blood pressure
HP:0004972	Elevated mean arterial pressure
HP:0005117	Elevated diastolic blood pressure
HP:0410054	Decreased circulating GABA concentration

Tissue	Cell type	Expression level	Reliability
colon	endothelial cells	Medium	Enhanced
kidney	cells in glomeruli	Low	Enhanced
placenta	endothelial cells	Low	Enhanced
placenta	syncytiotrophoblasts - cell body	High	Enhanced
placenta	syncytiotrophoblasts - microvilli	High	Enhanced

Summary of P29474

Gene: NOS3
Protein: Nitric oxide synthase 3

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P29474

Gene: NOS3 Protein: Nitric oxide synthase 3

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: NOS3
Protein: Nitric oxide synthase 3