ID NOS3_SHEEP Reviewed; 1205 AA. AC P79209; W5NV95; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2023, sequence version 2. DT 27-NOV-2024, entry version 117. 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}; 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 [LARGE SCALE GENOMIC DNA]. RC STRAIN=Texel; RX PubMed=20809919; DOI=10.1111/j.1365-2052.2010.02100.x; RA Archibald A.L., Cockett N.E., Dalrymple B.P., Faraut T., Kijas J.W., RA Maddox J.F., McEwan J.C., Hutton Oddy V., Raadsma H.W., Wade C., Wang J., RA Wang W., Xun X.; RT "The sheep genome reference sequence: a work in progress."; RL Anim. Genet. 41:449-453(2010). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 382-480. 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=2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 CC nitric oxide + 3 NADP(+) + 4 H2O; 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; CC Evidence={ECO:0000250|UniProtKB:P29474}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:P29476}; CC Note=Binds 1 FAD. {ECO:0000250|UniProtKB:P29476}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; CC Evidence={ECO:0000250|UniProtKB:P35228}; CC Note=Binds 1 FMN. {ECO:0000250|UniProtKB:P35228}; CC -!- COFACTOR: CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250|UniProtKB:P35228}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000250|UniProtKB:P35228}; 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; AMGL01089902; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AMGL01089903; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AMGL01089904; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AMGL01089905; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U76738; AAB40705.1; -; mRNA. DR AlphaFoldDB; P79209; -. DR SMR; P79209; -. DR STRING; 9940.ENSOARP00000002091; -. DR PaxDb; 9940-ENSOARP00000002091; -. DR Ensembl; ENSOART00000002141.1; ENSOARP00000002091.1; ENSOARG00000001979.1. DR eggNOG; KOG1158; Eukaryota. DR HOGENOM; CLU_001570_16_0_1; -. DR OMA; KGDFRIW; -. DR Proteomes; UP000002356; Chromosome 4. DR Bgee; ENSOARG00000001979; Expressed in mitral valve and 48 other cell types or tissues. 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: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; IEA:UniProtKB-EC. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:InterPro. DR CDD; cd00795; NOS_oxygenase_euk; 1. DR FunFam; 3.90.440.10:FF:000001; Endothelial nitric oxide synthase; 1. DR FunFam; 1.20.990.10:FF:000005; Nitric oxide synthase; 1. DR FunFam; 3.40.50.360:FF:000003; Nitric oxide synthase; 1. DR FunFam; 3.40.50.80:FF:000003; Nitric oxide synthase; 1. DR FunFam; 3.90.1230.10:FF:000001; Nitric oxide synthase, brain; 1. DR Gene3D; 3.40.50.360; -; 1. DR Gene3D; 3.90.440.10; Nitric Oxide Synthase;Heme Domain;Chain A domain 2; 1. DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1. DR Gene3D; 2.40.30.10; Translation factors; 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; IPR050607; NOS. 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 PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1. DR PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1. 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; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1. DR SUPFAM; SSF52218; Flavoproteins; 1. DR SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1. DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 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; Phosphoprotein; Reference proteome; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P29473" FT CHAIN 2..1205 FT /note="Nitric oxide synthase 3" FT /id="PRO_0000170947" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 26..73 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 100..489 FT /note="Interaction with NOSIP" FT /evidence="ECO:0000250|UniProtKB:P29474" FT REGION 796..850 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 COMPBIAS 830..849 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 /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 101 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000250|UniProtKB:P29474" 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 250 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 360 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 364 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 368 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 369 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" 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 450 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 463 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 478 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 529 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 530 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 531 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 533 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 575 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 576 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 657 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 664 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 690 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 694 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 781 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 803 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 939 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 941 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 942 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 957 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 959 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1018 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1051 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1080 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1081 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1087 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1089 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1091 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT MOD_RES 116 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29474" FT MOD_RES 498 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P29474" FT MOD_RES 618 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70313" FT MOD_RES 636 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29474" FT MOD_RES 641 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" FT /evidence="ECO:0000250|UniProtKB:P29474" FT MOD_RES 1181 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70313" FT CONFLICT 396 FT /note="M -> L (in Ref. 2; AAB40705)" FT /evidence="ECO:0000305" FT CONFLICT 415..416 FT /note="PP -> LA (in Ref. 2; AAB40705)" FT /evidence="ECO:0000305" SQ SEQUENCE 1205 AA; 132978 MW; CE5FDDE325A3A07F CRC64; MGNLKSVGQE PGPPCGLGLG LGFGLCGKQG PASPAPEPSW APAPATPQAP DHSPAPSSPT LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRR CLGSLVLPRK LQTRPSQGPP PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTYHLRES ELVFGAKQAW RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRLSA ITVFPQRTPG RGDFRIWNTQ LVRYAGYRQQ DGSVRGDPAN VEITELCIQH GWSPGNGRFD VLPLLLQAPD EAPELFVLPP ELVLEVPLEH PTLEWFAALG LRWYALPAVS NMLLEIGGLE FPAAPFSGWY MSTEIGTRNL CDPHRYNILE DVAVCMDLDT RTTSSMWKDK AAVEINLAVL HSFQPPKVTI VDHHAATVSF MKHLENEQKA RGGCPADWAW IVPPISGSLT PVFHQEMVNY VLSPAFRYQP DPWKGSAAKG AGITRKKTFK EVANAVKISA SLMGTLMAKR VKATILYASE TGRAQSYAQQ LGRLFRKAFD PRVLCMDEYD VVSLEHEALV LVVTSTFGNG DPPENGESFA AALMEMSGPY NSSPRPEQHR SYKIRFNSVS CSDPLVSSWR RKRKESSNTD SAGALGTLRF CVFGLGSRAY PHFCAFARAV DTRLEELGGE RLGQLGQGGE LRGQGEGFRG WGEGASRNAA SCETFCVGEE AKAAAQDIFS PKRSWKRQRY RLSTQAEGLQ LLPGLIHVHR RKMFQATVLS VENLQSSKST RATILVRLDT AGQEGLQYQP GDHISPHPPP RSSHRPGQGG PRVAPFSERP LMPRTPPPGG PPPSWVRDPR LPPCTLRQAL TFFLDITSPP SPRLLRLLST LAEEPSEQQE LETLSQDPRR YEEWKWFRCP TLLEVLEQFP SVALPAPLLL TQLPLLQPRY YSVSSAPSAH PGEVHLTVAV LALDTSRLCS PLHPAEVVKS GGVWGDKGGL TEGVLARAPS FRLPPDPYVP CILVGPGTGI APFRGFWQER LHDIESKGLQ RAAPTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVP RILATEGGME LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP DTPGP //