UniProtKB - Q28969 (NOS3_PIG)
Protein
Nitric oxide synthase, endothelial
Gene
NOS3
Organism
Sus scrofa (Pig)
Status
Functioni
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets (By similarity).By similarity
Catalytic activityi
- EC:1.14.13.39
Cofactori
Protein has several cofactor binding sites:- hemeBy similarity
- FADBy similarityNote: Binds 1 FAD.By similarity
- FMNBy similarityNote: Binds 1 FMN.By similarity
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterinBy similarityNote: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.By similarity
Activity regulationi
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 96 | ZincBy similarity | 1 | |
Metal bindingi | 101 | ZincBy similarity | 1 | |
Metal bindingi | 186 | Iron (heme axial ligand)By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 651 – 682 | FMNPROSITE-ProRule annotationAdd BLAST | 32 | |
Nucleotide bindingi | 795 – 806 | FADBy similarityAdd BLAST | 12 | |
Nucleotide bindingi | 937 – 947 | FADBy similarityAdd BLAST | 11 | |
Nucleotide bindingi | 1012 – 1030 | NADPBy similarityAdd BLAST | 19 | |
Nucleotide bindingi | 1110 – 1125 | NADPBy similarityAdd BLAST | 16 |
GO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
- flavin adenine dinucleotide binding Source: GO_Central
- FMN binding Source: GO_Central
- heme binding Source: InterPro
- metal ion binding Source: UniProtKB-KW
- NADP binding Source: InterPro
- NADPH-hemoprotein reductase activity Source: GO_Central
- nitric-oxide synthase activity Source: GO_Central
- oxidoreductase activity Source: GO_Central
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen Source: GO_Central
GO - Biological processi
- arginine catabolic process Source: GO_Central
- negative regulation of blood pressure Source: GO_Central
- nitric oxide biosynthetic process Source: GO_Central
- nitric oxide mediated signal transduction Source: GO_Central
- positive regulation of blood vessel diameter Source: AgBase
- positive regulation of guanylate cyclase activity Source: GO_Central
- response to hormone Source: GO_Central
- response to lipopolysaccharide Source: GO_Central
Keywordsi
Molecular function | Calmodulin-binding, Oxidoreductase |
Ligand | Calcium, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Nitric oxide synthase, endothelial (EC:1.14.13.39)Alternative name(s): Constitutive NOS Short name: cNOS EC-NOS Endothelial NOS Short name: eNOS NOS type III Short name: NOSIII |
Gene namesi | Name:NOS3 Synonyms:NOS |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity
Cytoskeleton
- cytoskeleton By similarity
Golgi apparatus
- Golgi apparatus By similarity
Other locations
- caveola By similarity
Note: Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle, which is favored by interaction with NOSIP and results in a reduced enzymatic activity.By similarity
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Cytosol
- cytosol Source: GO_Central
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Nucleus
- nucleus Source: GO_Central
Plasma Membrane
- caveola Source: UniProtKB-SubCell
- plasma membrane Source: GO_Central
Other locations
- vesicle membrane Source: GO_Central
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000170945 | 2 – 1205 | Nitric oxide synthase, endothelialAdd BLAST | 1204 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycineBy similarity | 1 | |
Lipidationi | 15 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 26 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 116 | Phosphoserine; by CDK5By similarity | 1 | |
Modified residuei | 497 | Phosphothreonine; by AMPKBy similarity | 1 | |
Modified residuei | 617 | PhosphoserineBy similarity | 1 | |
Modified residuei | 635 | PhosphoserineBy similarity | 1 | |
Modified residuei | 640 | PhosphoserineBy similarity | 1 | |
Modified residuei | 838 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1177 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1179 | Phosphoserine; by AMPKBy similarity | 1 | |
Modified residuei | 1181 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylation by AMPK at Ser-1179 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-497, resulting in inhibition of activity. Phosphorylation of Ser-116 by CDK5 reduces activity (By similarity).By similarity
Keywords - PTMi
Lipoprotein, Myristate, Palmitate, PhosphoproteinProteomic databases
PaxDbi | Q28969 |
PRIDEi | Q28969 |
PTM databases
iPTMneti | Q28969 |
Expressioni
Inductioni
Repressed by proinflammatory cytokines.
Interactioni
Subunit structurei
Homodimer.
Interacts with NOSIP and NOSTRIN (By similarity).
Interacts with HSP90AB1 (By similarity).
By similarityGO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 1149683, 3 interactors |
STRINGi | 9823.ENSSSCP00000017432 |
Chemistry databases
BindingDBi | Q28969 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 522 – 705 | Flavodoxin-likePROSITE-ProRule annotationAdd BLAST | 184 | |
Domaini | 758 – 1004 | FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST | 247 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 100 – 488 | Interaction with NOSIPBy similarityAdd BLAST | 389 | |
Regioni | 492 – 512 | Calmodulin-bindingSequence analysisAdd BLAST | 21 |
Sequence similaritiesi
Belongs to the NOS family.Curated
Phylogenomic databases
eggNOGi | KOG1158, Eukaryota |
InParanoidi | Q28969 |
OrthoDBi | 90349at2759 |
Family and domain databases
Gene3Di | 1.20.990.10, 1 hit 3.40.50.360, 1 hit 3.40.50.80, 1 hit |
InterProi | View protein in InterPro IPR003097, CysJ-like_FAD-binding IPR017927, FAD-bd_FR_type IPR001094, Flavdoxin-like IPR008254, Flavodoxin/NO_synth IPR001709, Flavoprot_Pyr_Nucl_cyt_Rdtase IPR029039, Flavoprotein-like_sf IPR039261, FNR_nucleotide-bd IPR023173, NADPH_Cyt_P450_Rdtase_alpha IPR012144, NOS_euk IPR004030, NOS_N IPR036119, NOS_N_sf IPR001433, OxRdtase_FAD/NAD-bd IPR017938, Riboflavin_synthase-like_b-brl |
Pfami | View protein in Pfam PF00667, FAD_binding_1, 1 hit PF00258, Flavodoxin_1, 1 hit PF00175, NAD_binding_1, 1 hit PF02898, NO_synthase, 1 hit |
PIRSFi | PIRSF000333, NOS, 1 hit |
PRINTSi | PR00369, FLAVODOXIN PR00371, FPNCR |
SUPFAMi | SSF52218, SSF52218, 1 hit SSF52343, SSF52343, 1 hit SSF56512, SSF56512, 1 hit SSF63380, SSF63380, 1 hit |
PROSITEi | View protein in PROSITE PS51384, FAD_FR, 1 hit PS50902, FLAVODOXIN_LIKE, 1 hit PS60001, NOS, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q28969-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APAPATPHAP
60 70 80 90 100
EHSPAPNSPT LTRPPEGPKF PRVKNWEVGS ITYDTLCAQS QQDGPCTPRR
110 120 130 140 150
CLGSLVLPRK LQSRPSPGPP PAEQLLSQAR DFINQYYSSI KRSGSQAHEE
160 170 180 190 200
RLQEVEAEVA TTGTYHLGES ELVFGAKQAW RNAPRCVGRI QWGKLQVFDA
210 220 230 240 250
RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRTPGR GDFRIWNSQL
260 270 280 290 300
VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
310 320 330 340 350
PPELFALPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF
360 370 380 390 400
PAAPFSGWYM STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA
410 420 430 440 450
AVEINLAVLH SYQLAKVTIV DHHAATASFM KHLENEQKAR GGCPADWAWI
460 470 480 490 500
VPPISGSLTP VFHQEMVNYV LSPAFRYQPD PWKGSAAKGT GIARKKTFKE
510 520 530 540 550
VANAVKISAS LMATVMPKRV KASILYASET VRAQSYAQQL GRLFRKAFDP
560 570 580 590 600
RVLCMDEYDV VSLEHETLVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN
610 620 630 640 650
GSPRPEQHRS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC
660 670 680 690 700
VFGLGSRAYP HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW
710 720 730 740 750
AQAAFQASCE TFCVGEDAKA AARDIFSPKR SWKRQRYRLS AQVEGLQLLP
760 770 780 790 800
GLVHVHRRKM FQATVLSVEN LQSSKSTRAT ILVRLDTEGQ EGLQYQPGDH
810 820 830 840 850
IGICPPNRTG LVEALLSRVE DPTPPTESVG VEQLEKGSPG GPPPSWVRDP
860 870 880 890 900
RLPPYTLRQA LTFFLDITSP PSPRLLRVLS TLAEEPSEQQ ELETLSQDPR
910 920 930 940 950
RYEEWKWFRC PTLLEVLEQF PSVALPTPLL LTQLALLQPR YYSVSSAPST
960 970 980 990 1000
YPGEIHPTVA VLAYRTQDGL GPLHYGVCST WLGQLKPGDP VPCFIRAAPS
1010 1020 1030 1040 1050
FRLPPDPSLP CILVGPGTGI APFRGFWQER LHDIESKGLQ PAPMTLVFGC
1060 1070 1080 1090 1100
RCSQLDHLYR DEVQDAQQRG VFGRVLTAFS REPDSPKTYV QDILRTELAA
1110 1120 1130 1140 1150
EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGNME LDEAGDVIGV
1160 1170 1180 1190 1200
LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWTFDPPGP
DTPGP
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U59924 mRNA Translation: AAB39539.1 U33832 mRNA Translation: AAA84933.1 |
RefSeqi | NP_999460.1, NM_214295.1 |
Genome annotation databases
GeneIDi | 397557 |
KEGGi | ssc:397557 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U59924 mRNA Translation: AAB39539.1 U33832 mRNA Translation: AAA84933.1 |
RefSeqi | NP_999460.1, NM_214295.1 |
3D structure databases
BMRBi | Q28969 |
SMRi | Q28969 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 1149683, 3 interactors |
STRINGi | 9823.ENSSSCP00000017432 |
Chemistry databases
BindingDBi | Q28969 |
ChEMBLi | CHEMBL3809 |
PTM databases
iPTMneti | Q28969 |
Proteomic databases
PaxDbi | Q28969 |
PRIDEi | Q28969 |
Genome annotation databases
GeneIDi | 397557 |
KEGGi | ssc:397557 |
Organism-specific databases
CTDi | 4846 |
Phylogenomic databases
eggNOGi | KOG1158, Eukaryota |
InParanoidi | Q28969 |
OrthoDBi | 90349at2759 |
Family and domain databases
Gene3Di | 1.20.990.10, 1 hit 3.40.50.360, 1 hit 3.40.50.80, 1 hit |
InterProi | View protein in InterPro IPR003097, CysJ-like_FAD-binding IPR017927, FAD-bd_FR_type IPR001094, Flavdoxin-like IPR008254, Flavodoxin/NO_synth IPR001709, Flavoprot_Pyr_Nucl_cyt_Rdtase IPR029039, Flavoprotein-like_sf IPR039261, FNR_nucleotide-bd IPR023173, NADPH_Cyt_P450_Rdtase_alpha IPR012144, NOS_euk IPR004030, NOS_N IPR036119, NOS_N_sf IPR001433, OxRdtase_FAD/NAD-bd IPR017938, Riboflavin_synthase-like_b-brl |
Pfami | View protein in Pfam PF00667, FAD_binding_1, 1 hit PF00258, Flavodoxin_1, 1 hit PF00175, NAD_binding_1, 1 hit PF02898, NO_synthase, 1 hit |
PIRSFi | PIRSF000333, NOS, 1 hit |
PRINTSi | PR00369, FLAVODOXIN PR00371, FPNCR |
SUPFAMi | SSF52218, SSF52218, 1 hit SSF52343, SSF52343, 1 hit SSF56512, SSF56512, 1 hit SSF63380, SSF63380, 1 hit |
PROSITEi | View protein in PROSITE PS51384, FAD_FR, 1 hit PS50902, FLAVODOXIN_LIKE, 1 hit PS60001, NOS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NOS3_PIG | |
Accessioni | Q28969Primary (citable) accession number: Q28969 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 161 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families