Nitric oxide synthase 3

Function

Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.

Classification

Family (Pfam)

PF00667 FAD_binding_1, PF00258 Flavodoxin_1, PF00175 NAD_binding_1, PF02898 NO_synthase

InterPro

CysJ-like_FAD-binding, FAD-bd_FR_type, Flavdoxin-like, Flavodoxin/NO_synth, Flavoprot_Pyr_Nucl_cyt_Rdtase, Flavoprotein-like_sf, FNR_nucleotide-bd, NADPH_Cyt_P450_Rdtase_alpha, NOS, NOS_dom_1, NOS_dom_2, NOS_dom_3, NOS_euk, NOS_N, NOS_N_sf, OxRdtase_FAD/NAD-bd, Riboflavin_synthase-like_b-brl

Functional cluster

Eukaryotic Transcription Factors & related

Experimental structures · PDB · 90

• 1M9J X-ray 2.43A
• 1M9K X-ray 2.01A
• 1M9M X-ray 1.96A
• 1M9Q X-ray 2.01A
• 1M9R X-ray 2.56A
• 1NIW X-ray 2.05A
• 2LL7 NMR
• 2MG5 NMR
• 2N8J NMR
• 3EAH X-ray 2.44A
• 3NOS X-ray 2.40A
• 4D1O X-ray 1.82A
• … and 78 more

A predicted model is available from AlphaFold.

Gene Ontology · 56

• GO:0005901 caveola
• GO:0005737 cytoplasm
• GO:0005856 cytoskeleton
• GO:0005829 cytosol
• GO:0030666 endocytic vesicle membrane
• GO:0005794 Golgi apparatus
• GO:0000139 Golgi membrane
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0003785 actin monomer binding
• GO:0034618 arginine binding
• GO:0046870 cadmium ion binding
• GO:0005516 calmodulin binding
• GO:0050660 flavin adenine dinucleotide binding
• GO:0010181 FMN binding
• GO:0020037 heme binding
• GO:0050661 NADP binding
• GO:0004517 nitric-oxide synthase activity
• GO:0097110 scaffold protein binding
• GO:0016175 superoxide-generating NAD(P)H oxidase activity
• GO:0034617 tetrahydrobiopterin binding
• GO:0003180 aortic valve morphogenesis
• GO:0097746 blood vessel diameter maintenance
• GO:0001974 blood vessel remodeling
• GO:0045454 cell redox homeostasis
• GO:0003203 endocardial cushion morphogenesis
• GO:0043542 endothelial cell migration
• GO:0048873 homeostasis of number of cells within a tissue
• GO:0006527 L-arginine catabolic process
• GO:0007005 mitochondrion organization
• GO:0070168 negative regulation of biomineral tissue development
• GO:0045776 negative regulation of blood pressure
• GO:0008285 negative regulation of cell population proliferation
• GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• GO:0014740 negative regulation of muscle hyperplasia
• GO:0010544 negative regulation of platelet activation
• GO:0006809 nitric oxide biosynthetic process
• GO:0007263 nitric oxide mediated signal transduction
• GO:0046209 nitric oxide metabolic process
• GO:0045766 positive regulation of angiogenesis
• GO:0043536 positive regulation of blood vessel endothelial cell migration
• GO:0010628 positive regulation of gene expression
• GO:0045747 positive regulation of Notch signaling pathway
• GO:0003184 pulmonary valve morphogenesis
• GO:0008217 regulation of blood pressure
• GO:0031644 regulation of nervous system process
• GO:0003100 regulation of systemic arterial blood pressure by endothelin
• GO:0019430 removal of superoxide radicals
• GO:0034405 response to fluid shear stress
• GO:0009408 response to heat
• GO:0009725 response to hormone
• GO:0032496 response to lipopolysaccharide
• GO:0014806 smooth muscle hyperplasia
• GO:0046146 tetrahydrobiopterin metabolic process
• GO:0042311 vasodilation
• GO:0060412 ventricular septum morphogenesis

Disease associations

• Moyamoya disease 8 MONDO:0980949

Drugs targeting this protein · 2

• TILARGININE ACETATE inhibitor
• TILARGININE inhibitor

Related proteins · sequence + function similarity

• Nitric oxide synthase 3 0.99
• Nitric oxide synthase 3 0.99
• Nitric oxide synthase 3 0.99
• Nitric oxide synthase 3 0.99
• Nitric oxide synthase 3 0.98
• Nitric oxide synthase 3 0.97
• Nitric oxide synthase 3 0.95
• ATP-dependent DNA helicase Q4 0.82
• Nitric oxide synthase, inducible 0.80
• UPF0575 protein C19orf67 0.78
• BLOC-2 complex member HPS6 0.78
• ATP-dependent DNA helicase Q4 0.77

Co-cited proteins · studied together in the literature

• Nitric oxide synthase-interacting protein 2 shared papers
• Nitric oxide synthase 1 2 shared papers
• Nostrin 2 shared papers
• Nitric oxide synthase, inducible 2 shared papers
• Nitric oxide synthase, inducible 1 shared papers
• Cyclin-dependent kinase 5 1 shared papers
• Nostrin 1 shared papers
• Heat shock protein HSP 90-beta 1 shared papers
• Nitric oxide synthase 1 1 shared papers
• Dynamin-2 1 shared papers
• Actin nucleation-promoting factor WASL 1 shared papers

Literature · 30 cited papers

• Biallelic variants in NOS3 and GUCY1A3, the two major genes of the nitric oxide pathway, cause moyamoya cerebral angiopathy. Hum. Genomics · 2023
• 2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors. Bioorg. Med. Chem. · 2022
• Structures of human constitutive nitric oxide synthases. Acta Crystallogr. D · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• LPS induces pp60c-src-mediated tyrosine phosphorylation of Hsp90 in lung vascular endothelial cells and mouse lung. Am. J. Physiol. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• CDK5 phosphorylates eNOS at Ser-113 and regulates NO production. J. Cell. Biochem. · 2010
• Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nat. Chem. Biol. · 2008
• Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity. FASEB J. · 2007
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J. Cell Sci. · 2005
• Cell cycle-regulated inactivation of endothelial NO synthase through NOSIP-dependent targeting to the cytoskeleton. Mol. Cell. Biol. · 2005
• … and 18 more in the literature graph