ID NOS3_SHEEP Reviewed; 99 AA. AC P79209; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 13-SEP-2023, entry version 112. DE RecName: Full=Nitric oxide synthase 3 {ECO:0000305}; DE EC=1.14.13.39 {ECO:0000250|UniProtKB:P29474}; DE AltName: Full=Constitutive NOS; DE Short=cNOS; DE AltName: Full=EC-NOS; DE AltName: Full=NOS type III; DE Short=NOSIII; DE AltName: Full=Nitric oxide synthase, endothelial {ECO:0000305}; DE Short=Endothelial NOS {ECO:0000305}; DE Short=eNOS {ECO:0000305}; DE Flags: Fragment; GN Name=NOS3; Synonyms=ENOS; OS Ovis aries (Sheep). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Caprinae; Ovis. OX NCBI_TaxID=9940; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Endothelial cell; RA Aguan K., Weiner C.P.; RT "Effect of hypoxia on the microvasculature of developing fetal brain of RT sheep: a studies on the expression pattern of constitutive forms of nitric RT oxide synthase."; RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases. 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 (By similarity). CC {ECO:0000250|UniProtKB:P29474}. 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 Evidence={ECO:0000250|UniProtKB:P29474}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898; CC Evidence={ECO:0000250|UniProtKB:P29474}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250}; CC Note=Binds 1 FAD. {ECO:0000250}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250}; CC Note=Binds 1 FMN. {ECO:0000250}; CC -!- COFACTOR: CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000250}; 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: Membrane, caveola {ECO:0000250}. Cytoplasm, CC cytoskeleton {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cell CC membrane {ECO:0000250}. 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 -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U76738; AAB40705.1; -; mRNA. DR AlphaFoldDB; P79209; -. DR SMR; P79209; -. DR STRING; 9940.ENSOARP00000002091; -. DR eggNOG; KOG1158; Eukaryota. DR Proteomes; UP000002356; 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; IEA:UniProtKB-SubCell. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004517; F:nitric-oxide synthase activity; IEA:UniProtKB-EC. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:InterPro. DR InterPro; IPR044943; NOS_dom_1. DR InterPro; IPR004030; NOS_N. DR InterPro; IPR036119; NOS_N_sf. DR PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1. DR PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1. DR Pfam; PF02898; NO_synthase; 1. DR SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1. PE 2: Evidence at transcript level; KW Calcium; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; FAD; KW Flavoprotein; FMN; Golgi apparatus; Heme; Iron; Membrane; Metal-binding; KW NADP; Oxidoreductase; Reference proteome. FT CHAIN <1..>99 FT /note="Nitric oxide synthase 3" FT /id="PRO_0000170947" FT BINDING 68 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 69 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 82 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 97 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P29474" FT NON_TER 1 FT NON_TER 99 SQ SEQUENCE 99 AA; 11034 MW; 82C3C765557031DA CRC64; VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV DHHAATVSFM KHLENEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYV LSPAFRYQP //