Primary Information
BoMiProt ID	Bomi7508
Protein Name	Nitric oxide synthase, endothelial/Constitutive NOS/Endothelial NOS/NOS type III/EC-NOS/eNOS/NOSIII
Organism	Bos taurus
Uniprot ID	P29473
Milk Fraction	Whey
Aminoacid Length	1205
Molecular Weight	133287
FASTA Sequence	Download
Gene Name	NOS3
Protein Existence Status	reviewed
Secondary Information
Protein Function	Produces nitric oxide (NO) which is important for vascular smooth muscle relaxation.NO then participate in cGMP-mediated phosphorylation and the formation of S-nitrosocysteine on proteins.NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis.
PTMs	Phosphorylation
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation	>sp|P29473|NOS3_BOVIN Nitric oxide synthase, endothelial OS=Bos taurus OX=9913 GN=NOS3 PE=1 SV=3 MGNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSRAPAPATPHAPDHSPAPNSPT LTRPPEGPKFPRVKNWELGSITYDTLCAQSQQDGPCTPRCCLGSLVLPRKLQTRPS*116PGPP PAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAW RNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRSAITVFPQRAPGR GDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDE APELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFSAAPFSGWYM STEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINLAVLHSFQLAKVTIV DHHAATVSFMKHLDNEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYILSPAFRYQPD PWKGSATKGAGITRKKT*497FKEVANAVKISASLMGTLMAKRVKATILYASETGRAQSYAQQL GRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYN SSPRPEQHKSYKIRFNS*617VSCSDPLVSSWRRKRKES*635SNTDS*640AGALGTLRFCVFGLGSRAYP HFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAKAAFQASCETFCVGEEAKA AAQDIFSPKRSWKRQRYRLSTQAEGLQLLPGLIHVHRRKMFQATVLSVENLQSSKSTRAT ILVRLDTAGQEGLQYQPGDHIGICPPNRPGLVEALLSRVEDPPPPTESVAVEQLEKGS*838PG GPPPSWVRDPRLPPCTLRQALTFFLDITSPPSPRLLRLLSTLAEEPSEQQELETLSQDPR RYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPNAHPGEVHLTVA VLAYRTQDGLGPLHYGVCSTWLSQLKTGDPVPCFIRGAPSFRLPPDPYVPCILVGPGTGI APFRGFWQERLHDIESKGLQPAPMTLVFGCRCSQLDHLYRDEVQDAQERGVFGRVLT*1177AFS REPDSPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATSVLQTVQRILATEGDME LDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERHLRGAVPWAFDPPGP DTPGP
SCOP	Class : Alpha and beta proteins (a+b) Fold : Nitric oxide (NO) synthase oxygenase domain Superfamily : Nitric oxide (NO) synthase oxygenase domain Family : Nitric oxide (NO) synthase oxygenase domain Domain Name : 1D0C A:67-482
CATH	Matched CATH superfamily 3.90.1230.10 3.90.340.10 3.90.440.10
Predicted Disorder Regions	31-60, 114-120, 838-847, 1195-1205
DisProt Annotation
TM Helix Prediction	No TM helices
Significance of PTMs	Thrombin rapidly phosphorylates eNOS at Ser1179 in cultured bovine aortic endothelial cells which plays a critical role in its activation by various agonists, such as vascular endothelial growth factor. Akt-mediated phosphorylation modulates eNOS uncoupling and greatly increases O2 generation from the enzyme at low Ca2+ concentrations, and PKCα-mediated phosphorylation alters the sensitivity of the enzyme to other negative regulatory signals.Akt specifically induces phosphorylation of Ser-1177 which is important for increase NO production from eNOS.and PKC specifically phosphorylates Thr-495 which is important to down-regulate NO generation.
PDB ID	1D0C,1D0O,1D1V,1D1W,1D1X,1D1Y,1DM6,1DM7,1DM8,1DMI,1DMJ,1DMK,1ED4,1ED5,1ED6,1FOI,1FOJ,1FOL,1FOO,1FOP,1I83,1NSE,1P6L,1P6M,1P6N,1Q2O,1RS8,1RS9,1ZZS,1ZZT,2G6O,2HX2,2NSE,3DQS,3DQT,3E7S,3JWW,3JWX,3JWY,3JWZ,3N5P,3N5Q,3N5R,3N5S,3N5T,3NLD,3NLE,3NLF,3NLG,3NLH,3NLI,3NLT,3NLU,3NSE,3PNH,3RQO, 3RQP,4C3A,4CAR,4CFT,4CTY,4CTZ,4CU0,4CU1,4CUL,4CUM,4CUN,4CVG,4CWV,4CWW,4CWX,4CWY,4CWZ,4CX0,4CX1,4CX2,4D33,4D34,4D35,4D36,4D37,4D38,4D39, 4D3A,4IMX,4JSK,4JSL,4JSM,4K5H,4K5I,4K5J,4K5K,4KCP,4KCQ,4KCR,4KCS,4LUW,4NSE,4UH7,4UH,
Bibliography	1.Chen CA, Druhan LJ, Varadharaj S, Chen YR, Zweier JL. Phosphorylation of endothelial nitric-oxide synthase regulates superoxide generation from the enzyme. J Biol Chem. 2008 Oct 3;283(40):27038-47. doi: 10.1074/jbc.M802269200. Epub 2008 Jul 13. PMID: 18622039; PMCID: PMC2556006. 2.Tenopoulou M, Doulias PT. Endothelial nitric oxide synthase-derived nitric oxide in the regulation of metabolism. F1000Res. 2020 Oct 1;9:F1000 Faculty Rev-1190. doi: 10.12688/f1000research.19998.1. PMID: 33042519; PMCID: PMC7531049. 3.Motley ED, Eguchi K, Patterson MM, Palmer PD, Suzuki H, Eguchi S. Mechanism of endothelial nitric oxide synthase phosphorylation and activation by thrombin. Hypertension. 2007 Mar;49(3):577-83. doi: 10.1161/01.HYP.0000255954.80025.34. Epub 2007 Jan 8. PMID: 17210830.