NOS3_BOVIN
ID NOS3_BOVIN Reviewed; 1205 AA.
AC P29473;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Nitric oxide synthase, endothelial;
DE EC=1.14.13.39;
DE AltName: Full=Constitutive NOS;
DE Short=cNOS;
DE AltName: Full=EC-NOS;
DE AltName: Full=Endothelial NOS;
DE Short=eNOS;
DE AltName: Full=NOS type III;
DE Short=NOSIII;
GN Name=NOS3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1378626; DOI=10.1073/pnas.89.14.6348;
RA Lamas S., Marsden P.A., Li G.K., Tempst P., Michel T.;
RT "Endothelial nitric oxide synthase: molecular cloning and characterization
RT of a distinct constitutive enzyme isoform.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6348-6352(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1385480; DOI=10.1172/jci116092;
RA Nishida K., Harrison D.G., Navas J.P., Fisher A.A., Dockery S.P.,
RA Uematsu M., Nerem R.M., Alexander R.W., Murphy T.J.;
RT "Molecular cloning and characterization of the constitutive bovine aortic
RT endothelial cell nitric oxide synthase.";
RL J. Clin. Invest. 90:2092-2096(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Aortic endothelium;
RX PubMed=1379225; DOI=10.1016/s0021-9258(19)49528-8;
RA Sessa W.C., Harrison J.K., Barber C.M., Zeng D., Durieux M.E.,
RA D'Angelo D.D., Lynch K.R., Peach M.J.;
RT "Molecular cloning and expression of a cDNA encoding endothelial cell
RT nitric oxide synthase.";
RL J. Biol. Chem. 267:15274-15276(1992).
RN [4]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=7682550; DOI=10.1016/s0021-9258(18)52889-1;
RA Busconi L., Michel T.;
RT "Endothelial nitric oxide synthase. N-terminal myristoylation determines
RT subcellular localization.";
RL J. Biol. Chem. 268:8410-8413(1993).
RN [5]
RP PALMITOYLATION AT CYS-15 AND CYS-26.
RX PubMed=8524847; DOI=10.1073/pnas.92.25.11776;
RA Robinson L.J., Michel T.;
RT "Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase
RT identifies a novel motif for dual acylation and subcellular targeting.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11776-11780(1995).
RN [6]
RP PHOSPHORYLATION AT THR-497; SER-635 AND SER-1179.
RX PubMed=12384459; DOI=10.1152/ajpheart.00214.2002;
RA Boo Y.C., Hwang J., Sykes M., Michell B.J., Kemp B.E., Lum H., Jo H.;
RT "Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein
RT kinase A-dependent mechanism.";
RL Am. J. Physiol. 283:H1819-H1828(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17071725; DOI=10.1152/ajpheart.00990.2006;
RA Mukhopadhyay S., Xu F., Sehgal P.B.;
RT "Aberrant cytoplasmic sequestration of eNOS in endothelial cells after
RT monocrotaline, hypoxia, and senescence: live-cell caveolar and cytoplasmic
RT NO imaging.";
RL Am. J. Physiol. 292:H1373-H1389(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 67-482.
RX PubMed=9875848; DOI=10.1016/s0092-8674(00)81718-3;
RA Raman C.S., Li H., Martasek P., Kral V., Masters B.S.S., Poulos T.L.;
RT "Crystal structure of constitutive endothelial nitric oxide synthase: a
RT paradigm for pterin function involving a novel metal center.";
RL Cell 95:939-950(1998).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 67-482.
RX PubMed=11051558; DOI=10.1016/s0162-0134(00)00099-4;
RA Li H., Raman C.S., Martasek P., Kral V., Masters B.S.S., Poulos T.L.;
RT "Mapping the active site polarity in structures of endothelial nitric oxide
RT synthase heme domain complexed with isothioureas.";
RL J. Inorg. Biochem. 81:133-139(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS).
RX PubMed=11331003; DOI=10.1021/bi002658v;
RA Li H., Raman C.S., Martasek P., Masters B.S.S., Poulos T.L.;
RT "Crystallographic studies on endothelial nitric oxide synthase complexed
RT with nitric oxide and mechanism-based inhibitors.";
RL Biochemistry 40:5399-5406(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
RX PubMed=11695891; DOI=10.1021/bi010957u;
RA Raman C.S., Li H., Martasek P., Southan G., Masters B.S.S., Poulos T.L.;
RT "Crystal structure of nitric oxide synthase bound to nitro indazole reveals
RT a novel inactivation mechanism.";
RL Biochemistry 40:13448-13455(2001).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS).
RX PubMed=11331290; DOI=10.1074/jbc.m102255200;
RA Raman C.S., Li H., Martasek P., Babu B.R., Griffith O.W., Southan G.,
RA Masters B.S.S., Poulos T.L.;
RT "Implications for isoform-selective inhibitor design derived from the
RT binding mode of bulky isothioureas to the heme domain of endothelial
RT nitric-oxide synthase.";
RL J. Biol. Chem. 276:26486-26491(2001).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS).
RX PubMed=11590164; DOI=10.1074/jbc.m011469200;
RA Kotsonis P., Frohlich L.G., Raman C.S., Li H., Berg M., Gerwig R.,
RA Groehn V., Kang Y., Al-Masoudi N., Taghavi-Moghadam S., Mohr D., Munch U.,
RA Schnabel J., Martasek P., Masters B.S.S., Strobel H., Poulos T., Matter H.,
RA Pfleiderer W., Schmidt H.H.H.W.;
RT "Structural basis for pterin antagonism in nitric-oxide synthase.
RT Development of novel 4-oxo-pteridine antagonists of (6R)-5,6,7,8-
RT tetrahydrobiopterin.";
RL J. Biol. Chem. 276:49133-49141(2001).
CC -!- FUNCTION: Produces nitric oxide (NO) which is implicated in vascular
CC smooth muscle relaxation through a cGMP-mediated signal transduction
CC pathway. NO mediates vascular endothelial growth factor (VEGF)-induced
CC angiogenesis in coronary vessels and promotes blood clotting through
CC the activation of platelets.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline
CC + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD.;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Note=Binds 1 FMN.;
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560;
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme.;
CC -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin. Inhibited by
CC NOSIP and NOSTRIN (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with NOSIP and NOSTRIN (By similarity).
CC Interacts with HSP90AB1 (By similarity). Forms a complex with ASL, ASS1
CC and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis
CC and citrulline recycling while channeling extracellular L-arginine to
CC nitric oxide synthesis pathway (By similarity).
CC {ECO:0000250|UniProtKB:P29474, ECO:0000250|UniProtKB:P70313}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17071725}.
CC Membrane, caveola {ECO:0000269|PubMed:17071725}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Golgi apparatus
CC {ECO:0000269|PubMed:17071725}. Note=Specifically associates with actin
CC cytoskeleton in the G2 phase of the cell cycle; which is favored by
CC interaction with NOSIP and results in a reduced enzymatic activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation by AMPK at Ser-1179 in the presence of Ca(2+)-
CC calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin,
CC AMPK also phosphorylates Thr-497, resulting in inhibition of activity.
CC Phosphorylation of Ser-116 by CDK5 reduces activity (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR EMBL; M99057; AAA30667.1; -; mRNA.
DR EMBL; M89952; AAA30494.1; -; mRNA.
DR EMBL; M95674; AAA30669.1; -; mRNA.
DR PIR; A38943; A38943.
DR PDB; 1D0C; X-ray; 1.65 A; A/B=39-482.
DR PDB; 1D0O; X-ray; 1.95 A; A/B=39-482.
DR PDB; 1D1V; X-ray; 1.93 A; A/B=39-482.
DR PDB; 1D1W; X-ray; 2.00 A; A/B=39-482.
DR PDB; 1D1X; X-ray; 2.00 A; A/B=39-482.
DR PDB; 1D1Y; X-ray; 2.20 A; A/B=39-482.
DR PDB; 1DM6; X-ray; 1.95 A; A/B=39-482.
DR PDB; 1DM7; X-ray; 2.10 A; A/B=39-482.
DR PDB; 1DM8; X-ray; 2.25 A; A/B=39-482.
DR PDB; 1DMI; X-ray; 2.00 A; A/B=39-482.
DR PDB; 1DMJ; X-ray; 2.35 A; A/B=39-482.
DR PDB; 1DMK; X-ray; 1.90 A; A/B=39-482.
DR PDB; 1ED4; X-ray; 1.86 A; A/B=39-482.
DR PDB; 1ED5; X-ray; 1.80 A; A/B=39-482.
DR PDB; 1ED6; X-ray; 2.05 A; A/B=39-482.
DR PDB; 1FOI; X-ray; 1.93 A; A/B=39-482.
DR PDB; 1FOJ; X-ray; 2.10 A; A/B=39-482.
DR PDB; 1FOL; X-ray; 2.20 A; A/B=39-482.
DR PDB; 1FOO; X-ray; 2.00 A; A/B=39-482.
DR PDB; 1FOP; X-ray; 2.30 A; A/B=39-482.
DR PDB; 1I83; X-ray; 2.00 A; A/B=39-482.
DR PDB; 1NSE; X-ray; 1.90 A; A/B=39-482.
DR PDB; 1P6L; X-ray; 2.35 A; A/B=67-483.
DR PDB; 1P6M; X-ray; 2.27 A; A/B=67-483.
DR PDB; 1P6N; X-ray; 2.50 A; A/B=67-483.
DR PDB; 1Q2O; X-ray; 1.74 A; A/B=67-482.
DR PDB; 1RS8; X-ray; 2.30 A; A/B=67-482.
DR PDB; 1RS9; X-ray; 2.22 A; A/B=67-482.
DR PDB; 1ZZS; X-ray; 1.85 A; A/B=67-482.
DR PDB; 1ZZT; X-ray; 2.14 A; A/B=67-482.
DR PDB; 2G6O; X-ray; 1.90 A; A/B=67-482.
DR PDB; 2HX2; X-ray; 1.95 A; A/B=67-482.
DR PDB; 2NSE; X-ray; 2.34 A; A/B=39-482.
DR PDB; 3DQS; X-ray; 2.03 A; A/B=67-482.
DR PDB; 3DQT; X-ray; 2.54 A; A/B=67-482.
DR PDB; 3E7S; X-ray; 2.50 A; A/B=57-487.
DR PDB; 3JWW; X-ray; 2.20 A; A/B=39-482.
DR PDB; 3JWX; X-ray; 2.00 A; A/B=39-482.
DR PDB; 3JWY; X-ray; 2.24 A; A/B=39-482.
DR PDB; 3JWZ; X-ray; 2.40 A; A/B=39-482.
DR PDB; 3N5P; X-ray; 2.39 A; A/B=39-482.
DR PDB; 3N5Q; X-ray; 2.90 A; A/B=39-482.
DR PDB; 3N5R; X-ray; 2.57 A; A/B=39-482.
DR PDB; 3N5S; X-ray; 2.18 A; A/B=39-482.
DR PDB; 3N5T; X-ray; 2.52 A; A/B=39-482.
DR PDB; 3NLD; X-ray; 2.28 A; A/B=39-482.
DR PDB; 3NLE; X-ray; 1.95 A; A/B=39-482.
DR PDB; 3NLF; X-ray; 2.32 A; A/B=39-482.
DR PDB; 3NLG; X-ray; 2.38 A; A/B=39-482.
DR PDB; 3NLH; X-ray; 2.10 A; A/B=39-482.
DR PDB; 3NLI; X-ray; 1.98 A; A/B=39-482.
DR PDB; 3NLT; X-ray; 2.74 A; A/B=39-482.
DR PDB; 3NLU; X-ray; 2.65 A; A/B=39-482.
DR PDB; 3NSE; X-ray; 2.10 A; A/B=39-482.
DR PDB; 3PNH; X-ray; 1.93 A; A/B=67-482.
DR PDB; 3RQO; X-ray; 2.08 A; A/B=40-482.
DR PDB; 3RQP; X-ray; 2.35 A; A/B=40-482.
DR PDB; 4C3A; X-ray; 2.20 A; A/B=40-482.
DR PDB; 4CAR; X-ray; 2.05 A; A/B=40-482.
DR PDB; 4CFT; X-ray; 1.79 A; A/B=40-482.
DR PDB; 4CTY; X-ray; 2.30 A; A/B=40-482.
DR PDB; 4CTZ; X-ray; 2.01 A; A/B=40-482.
DR PDB; 4CU0; X-ray; 2.08 A; A/B=40-482.
DR PDB; 4CU1; X-ray; 1.89 A; A/B=40-482.
DR PDB; 4CUL; X-ray; 2.23 A; A/B=40-482.
DR PDB; 4CUM; X-ray; 2.33 A; A/B=40-482.
DR PDB; 4CUN; X-ray; 2.48 A; A/B=40-482.
DR PDB; 4CVG; X-ray; 2.31 A; A/B=40-482.
DR PDB; 4CWV; X-ray; 2.34 A; A/B=40-482.
DR PDB; 4CWW; X-ray; 2.16 A; A/B=40-482.
DR PDB; 4CWX; X-ray; 2.15 A; A/B=40-482.
DR PDB; 4CWY; X-ray; 2.15 A; A/B=40-482.
DR PDB; 4CWZ; X-ray; 2.08 A; A/B=40-482.
DR PDB; 4CX0; X-ray; 2.20 A; A/B=40-482.
DR PDB; 4CX1; X-ray; 2.13 A; A/B=40-482.
DR PDB; 4CX2; X-ray; 2.04 A; A/B=40-482.
DR PDB; 4D33; X-ray; 2.09 A; A/B=40-482.
DR PDB; 4D34; X-ray; 2.25 A; A/B=40-482.
DR PDB; 4D35; X-ray; 2.18 A; A/B=40-482.
DR PDB; 4D36; X-ray; 2.05 A; A/B=40-482.
DR PDB; 4D37; X-ray; 2.10 A; A/B=40-482.
DR PDB; 4D38; X-ray; 2.30 A; A/B=40-482.
DR PDB; 4D39; X-ray; 2.00 A; A/B=40-482.
DR PDB; 4D3A; X-ray; 2.25 A; A/B=40-482.
DR PDB; 4IMX; X-ray; 2.25 A; A/B=40-482.
DR PDB; 4JSK; X-ray; 2.28 A; A/B=40-482.
DR PDB; 4JSL; X-ray; 2.04 A; A/B=40-482.
DR PDB; 4JSM; X-ray; 2.25 A; A/B=40-482.
DR PDB; 4K5H; X-ray; 2.25 A; A/B=40-482.
DR PDB; 4K5I; X-ray; 2.08 A; A/B=40-482.
DR PDB; 4K5J; X-ray; 2.36 A; A/B=40-482.
DR PDB; 4K5K; X-ray; 2.00 A; A/B=40-482.
DR PDB; 4KCP; X-ray; 2.07 A; A/B=40-482.
DR PDB; 4KCQ; X-ray; 2.03 A; A/B=40-482.
DR PDB; 4KCR; X-ray; 2.09 A; A/B=40-482.
DR PDB; 4KCS; X-ray; 2.05 A; A/B=40-482.
DR PDB; 4LUW; X-ray; 2.25 A; A/B=41-482.
DR PDB; 4NSE; X-ray; 1.95 A; A/B=39-482.
DR PDB; 4UH7; X-ray; 2.23 A; A/B=40-482.
DR PDB; 4UH8; X-ray; 2.30 A; A/B=40-482.
DR PDB; 4UH9; X-ray; 2.14 A; A/B=40-482.
DR PDB; 4UHA; X-ray; 2.20 A; A/B=40-482.
DR PDB; 4UPQ; X-ray; 2.03 A; A/B=40-482.
DR PDB; 4UPR; X-ray; 1.93 A; A/B=40-482.
DR PDB; 4UPS; X-ray; 1.95 A; A/B=40-482.
DR PDB; 4UPT; X-ray; 2.20 A; A/B=40-482.
DR PDB; 5ADJ; X-ray; 2.22 A; A/B=40-482.
DR PDB; 5ADK; X-ray; 1.80 A; A/B=40-482.
DR PDB; 5ADL; X-ray; 2.21 A; A/B=40-482.
DR PDB; 5ADM; X-ray; 2.20 A; A/B=40-482.
DR PDB; 5ADN; X-ray; 2.00 A; A/B=40-482.
DR PDB; 5FJ2; X-ray; 2.05 A; A/B=40-482.
DR PDB; 5FJ3; X-ray; 2.20 A; A/B=40-482.
DR PDB; 5FVY; X-ray; 2.10 A; A/B=40-482.
DR PDB; 5FVZ; X-ray; 2.05 A; A/B=40-482.
DR PDB; 5NSE; X-ray; 1.90 A; A/B=39-482.
DR PDB; 5UOD; X-ray; 2.01 A; A/B=40-482.
DR PDB; 5VV6; X-ray; 2.00 A; A/B=40-482.
DR PDB; 5VV7; X-ray; 2.20 A; A/B=40-482.
DR PDB; 5VV8; X-ray; 2.15 A; A/B=40-482.
DR PDB; 5VV9; X-ray; 2.50 A; A/B=40-482.
DR PDB; 5VVA; X-ray; 2.55 A; A/B=40-482.
DR PDB; 5VVG; X-ray; 2.30 A; A/B=40-482.
DR PDB; 5VVN; X-ray; 2.40 A; A/B=40-482.
DR PDB; 6NSE; X-ray; 2.35 A; A/B=39-482.
DR PDB; 7NSE; X-ray; 2.35 A; A/B=39-482.
DR PDB; 8NSE; X-ray; 2.25 A; A/B=39-482.
DR PDB; 9NSE; X-ray; 2.24 A; A/B=39-482.
DR PDBsum; 1D0C; -.
DR PDBsum; 1D0O; -.
DR PDBsum; 1D1V; -.
DR PDBsum; 1D1W; -.
DR PDBsum; 1D1X; -.
DR PDBsum; 1D1Y; -.
DR PDBsum; 1DM6; -.
DR PDBsum; 1DM7; -.
DR PDBsum; 1DM8; -.
DR PDBsum; 1DMI; -.
DR PDBsum; 1DMJ; -.
DR PDBsum; 1DMK; -.
DR PDBsum; 1ED4; -.
DR PDBsum; 1ED5; -.
DR PDBsum; 1ED6; -.
DR PDBsum; 1FOI; -.
DR PDBsum; 1FOJ; -.
DR PDBsum; 1FOL; -.
DR PDBsum; 1FOO; -.
DR PDBsum; 1FOP; -.
DR PDBsum; 1I83; -.
DR PDBsum; 1NSE; -.
DR PDBsum; 1P6L; -.
DR PDBsum; 1P6M; -.
DR PDBsum; 1P6N; -.
DR PDBsum; 1Q2O; -.
DR PDBsum; 1RS8; -.
DR PDBsum; 1RS9; -.
DR PDBsum; 1ZZS; -.
DR PDBsum; 1ZZT; -.
DR PDBsum; 2G6O; -.
DR PDBsum; 2HX2; -.
DR PDBsum; 2NSE; -.
DR PDBsum; 3DQS; -.
DR PDBsum; 3DQT; -.
DR PDBsum; 3E7S; -.
DR PDBsum; 3JWW; -.
DR PDBsum; 3JWX; -.
DR PDBsum; 3JWY; -.
DR PDBsum; 3JWZ; -.
DR PDBsum; 3N5P; -.
DR PDBsum; 3N5Q; -.
DR PDBsum; 3N5R; -.
DR PDBsum; 3N5S; -.
DR PDBsum; 3N5T; -.
DR PDBsum; 3NLD; -.
DR PDBsum; 3NLE; -.
DR PDBsum; 3NLF; -.
DR PDBsum; 3NLG; -.
DR PDBsum; 3NLH; -.
DR PDBsum; 3NLI; -.
DR PDBsum; 3NLT; -.
DR PDBsum; 3NLU; -.
DR PDBsum; 3NSE; -.
DR PDBsum; 3PNH; -.
DR PDBsum; 3RQO; -.
DR PDBsum; 3RQP; -.
DR PDBsum; 4C3A; -.
DR PDBsum; 4CAR; -.
DR PDBsum; 4CFT; -.
DR PDBsum; 4CTY; -.
DR PDBsum; 4CTZ; -.
DR PDBsum; 4CU0; -.
DR PDBsum; 4CU1; -.
DR PDBsum; 4CUL; -.
DR PDBsum; 4CUM; -.
DR PDBsum; 4CUN; -.
DR PDBsum; 4CVG; -.
DR PDBsum; 4CWV; -.
DR PDBsum; 4CWW; -.
DR PDBsum; 4CWX; -.
DR PDBsum; 4CWY; -.
DR PDBsum; 4CWZ; -.
DR PDBsum; 4CX0; -.
DR PDBsum; 4CX1; -.
DR PDBsum; 4CX2; -.
DR PDBsum; 4D33; -.
DR PDBsum; 4D34; -.
DR PDBsum; 4D35; -.
DR PDBsum; 4D36; -.
DR PDBsum; 4D37; -.
DR PDBsum; 4D38; -.
DR PDBsum; 4D39; -.
DR PDBsum; 4D3A; -.
DR PDBsum; 4IMX; -.
DR PDBsum; 4JSK; -.
DR PDBsum; 4JSL; -.
DR PDBsum; 4JSM; -.
DR PDBsum; 4K5H; -.
DR PDBsum; 4K5I; -.
DR PDBsum; 4K5J; -.
DR PDBsum; 4K5K; -.
DR PDBsum; 4KCP; -.
DR PDBsum; 4KCQ; -.
DR PDBsum; 4KCR; -.
DR PDBsum; 4KCS; -.
DR PDBsum; 4LUW; -.
DR PDBsum; 4NSE; -.
DR PDBsum; 4UH7; -.
DR PDBsum; 4UH8; -.
DR PDBsum; 4UH9; -.
DR PDBsum; 4UHA; -.
DR PDBsum; 4UPQ; -.
DR PDBsum; 4UPR; -.
DR PDBsum; 4UPS; -.
DR PDBsum; 4UPT; -.
DR PDBsum; 5ADJ; -.
DR PDBsum; 5ADK; -.
DR PDBsum; 5ADL; -.
DR PDBsum; 5ADM; -.
DR PDBsum; 5ADN; -.
DR PDBsum; 5FJ2; -.
DR PDBsum; 5FJ3; -.
DR PDBsum; 5FVY; -.
DR PDBsum; 5FVZ; -.
DR PDBsum; 5NSE; -.
DR PDBsum; 5UOD; -.
DR PDBsum; 5VV6; -.
DR PDBsum; 5VV7; -.
DR PDBsum; 5VV8; -.
DR PDBsum; 5VV9; -.
DR PDBsum; 5VVA; -.
DR PDBsum; 5VVG; -.
DR PDBsum; 5VVN; -.
DR PDBsum; 6NSE; -.
DR PDBsum; 7NSE; -.
DR PDBsum; 8NSE; -.
DR PDBsum; 9NSE; -.
DR AlphaFoldDB; P29473; -.
DR BMRB; P29473; -.
DR SMR; P29473; -.
DR DIP; DIP-42217N; -.
DR ELM; P29473; -.
DR IntAct; P29473; 2.
DR MINT; P29473; -.
DR STRING; 9913.ENSBTAP00000023515; -.
DR BindingDB; P29473; -.
DR ChEMBL; CHEMBL4802; -.
DR iPTMnet; P29473; -.
DR SwissPalm; P29473; -.
DR PaxDb; P29473; -.
DR PRIDE; P29473; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; P29473; -.
DR BRENDA; 1.14.13.39; 908.
DR EvolutionaryTrace; P29473; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL.
DR GO; GO:0007005; P:mitochondrion organization; IMP:BHF-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IMP:BHF-UCL.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR044940; NOS_dom_2.
DR InterPro; IPR044944; NOS_dom_3.
DR InterPro; IPR012144; NOS_euk.
DR InterPro; IPR004030; NOS_N.
DR InterPro; IPR036119; NOS_N_sf.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF02898; NO_synthase; 1.
DR PIRSF; PIRSF000333; NOS; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF56512; SSF56512; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Blood coagulation; Calcium; Calmodulin-binding;
KW Cell membrane; Cytoplasm; Cytoskeleton; FAD; Flavoprotein; FMN;
KW Golgi apparatus; Heme; Hemostasis; Iron; Lipoprotein; Membrane;
KW Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..1205
FT /note="Nitric oxide synthase, endothelial"
FT /id="PRO_0000170941"
FT DOMAIN 522..705
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 758..1004
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..488
FT /note="Interaction with NOSIP"
FT /evidence="ECO:0000250"
FT REGION 492..512
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT REGION 820..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..66
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 104
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 186
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 249
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 358
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 359
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 363
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 368
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 448
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 449
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 462
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 477
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 651..682
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 795..806
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 937..947
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1012..1030
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1110..1125
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 116
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT MOD_RES 497
FT /note="Phosphothreonine; by AMPK and PKA"
FT /evidence="ECO:0000269|PubMed:12384459"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12384459"
FT MOD_RES 640
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT MOD_RES 838
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT MOD_RES 1177
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 1179
FT /note="Phosphoserine; by AMPK, PDPK1 and PKA"
FT /evidence="ECO:0000269|PubMed:12384459"
FT MOD_RES 1181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:7682550"
FT LIPID 15
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8524847"
FT LIPID 26
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8524847"
FT CONFLICT 100
FT /note="C -> R (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="Y -> I (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 318..328
FT /note="EHPTLEWFAAL -> GAPHTGVVRGP (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="S -> Y (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="T -> P (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="T -> A (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 804..805
FT /note="CP -> SA (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 857
FT /note="L -> V (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 907..908
FT /note="WF -> LV (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT CONFLICT 1042
FT /note="A -> H (in Ref. 3; AAA30669)"
FT /evidence="ECO:0000305"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:3E7S"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1D0C"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1DMK"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:8NSE"
FT HELIX 122..139
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 146..162
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 206..221
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:4CFT"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:4NSE"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 270..278
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 323..328
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 348..351
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 361..365
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 367..370
FT /evidence="ECO:0007829|PDB:1D0C"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 378..384
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 396..414
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 422..440
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 447..450
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 453..455
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:1D0C"
FT HELIX 460..463
FT /evidence="ECO:0007829|PDB:1D0C"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:3E7S"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:1D0C"
SQ SEQUENCE 1205 AA; 133287 MW; 5DC8FF4F25870281 CRC64;
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSR APAPATPHAP DHSPAPNSPT
LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRC CLGSLVLPRK LQTRPSPGPP
PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTYHLRES ELVFGAKQAW
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRAPGR
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
APELFVLPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV
DHHAATVSFM KHLDNEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYI LSPAFRYQPD
PWKGSATKGA GITRKKTFKE VANAVKISAS LMGTLMAKRV KATILYASET GRAQSYAQQL
GRLFRKAFDP RVLCMDEYDV VSLEHEALVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN
SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AKAAFQASCE TFCVGEEAKA
AAQDIFSPKR SWKRQRYRLS TQAEGLQLLP GLIHVHRRKM FQATVLSVEN LQSSKSTRAT
ILVRLDTAGQ EGLQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPTESVA VEQLEKGSPG
GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPRLLRLLS TLAEEPSEQQ ELETLSQDPR
RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPNA HPGEVHLTVA
VLAYRTQDGL GPLHYGVCST WLSQLKTGDP VPCFIRGAPS FRLPPDPYVP CILVGPGTGI
APFRGFWQER LHDIESKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP
DTPGP
