NOS3_CANLF
ID NOS3_CANLF Reviewed; 1205 AA.
AC Q9TUX8;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 124.
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; Synonyms=NOS;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=10442857; DOI=10.1006/niox.1999.0234;
RA Schwemmer M., Bassenge E.;
RT "Assembly and characterization of canine heart endothelial nitric oxide
RT synthase cDNA and 5'-flanking sequence by homology (RT-)PCR cloning.";
RL Nitric Oxide 3:254-264(1999).
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). {ECO:0000250}.
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; 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 -!- 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; AF143503; AAD52161.1; -; mRNA.
DR AlphaFoldDB; Q9TUX8; -.
DR BMRB; Q9TUX8; -.
DR SMR; Q9TUX8; -.
DR STRING; 9612.ENSCAFP00000006985; -.
DR PaxDb; Q9TUX8; -.
DR PRIDE; Q9TUX8; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; Q9TUX8; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0012506; C:vesicle membrane; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0010181; F:FMN binding; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006527; P:arginine catabolic process; IBA:GO_Central.
DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IBA:GO_Central.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Calcium; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; FAD;
KW Flavoprotein; FMN; Golgi apparatus; Heme; Iron; Lipoprotein; Membrane;
KW Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein;
KW 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, endothelial"
FT /id="PRO_0000289580"
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 819..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..67
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 /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
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"
FT /evidence="ECO:0000250|UniProtKB:P29473"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29473"
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"
FT /evidence="ECO:0000250|UniProtKB:P29473"
FT MOD_RES 1181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT LIPID 15
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 26
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1205 AA; 133046 MW; C150CDEB01685BA5 CRC64;
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPTSEPSR APALAPPPSP PPAPDHSSPP
LTRPPDGPKF PRVKNWEVGS ITYDTLSAQS QQDGPCTPRR CLGSLVFPRK LQSRPSQNPA
PPEQLLSQAR DFISQYYSSI KRSGSQAHEQ RLQEVEAEVA ATGTYQLRES ELVFGAKQAW
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRASGR
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
PPELFALPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF PAAPFSGWYM
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SYQLAKVTIV
DHHAATASFM KHLENEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYV LSPAFRYQTD
PWKGSASKGA GVTRKKTFKE VANAVKISAS LMGTVMAKRV KATILYGSET GRAQSYAQQL
GRLFRKAFDP RVLCMDEYDV VSLEHETLVL VVTSTFGNGD PPENGESFAA ALMEMSGSYN
SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESRNTDS AGALGTLRFC VFGLGSRAYP
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFGGW AQAAFQASWE TFCVGEDAKA
AARDIFSPKR TWKRQRYRLS AQAEGLQLLP GLIHVHRRKM VQATVLAVEN LQSSKSTRAT
ILVRLDTGSQ EALQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPGEPVA VEQLEKGSPG
GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPQLLRLLS TLAEESSEQQ ELESLSQDPR
RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPSA HPGEIHLTVA
VLAYRTQDGL GPLHYGVCST WLSQLKAGDP VPCFIRGAPS FRLPPDPSLP CILVGPGTGI
APFRGFWQGR LHDIYSKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQQRG VFGRVLTAFS
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWALDPPGP
DTVGP
