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Symbol NOS3 contributors: mct - updated : 03-02-2015
HGNC name nitric oxide synthase 3 (endothelial cell)
HGNC id 7876
Location 7q36.1      Physical location : 150.688.143 - 150.711.686
Synonym name constitutive endothelial nitric oxide synthase
Synonym symbol(s) ECNOS, ENOS, NOS III
TYPE functioning gene
STRUCTURE 23.55 kb     27 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure two promoters
MAPPING cloned Y linked N status confirmed
Physical map
LOC389599 7 similar to amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2; ILP-interacting protein ILPIPA hIAN7 7q36.1 immune associated nucleotide ATQL3 7q36 antiquitin-like 3 HIMAP4 7q36.1 immunity associated protein 4 LOC392149 7 similar to transient receptor potential cation channel, subfamily C, member 6; transient receptor potential channel 6 hIAN2 7q36.1 human immune associated nucleotide 2 HIMAP2 7q36.1 immunity associated protein 2 IMAP1 7q36.1 immunity associated protein 1 IAN4L1 7q32-q36 immune associated nucleotide 4 like 1 (mouse) LOC392150 7 similar to immune associated nucleotide 4 like 1; immunity associated protein 3 LOC392151 7 similar to BET1 homolog (Golgi vesicular membrane trafficking protein p18) (hBET1) LR8 7q36.1 LR8 protein HCA112 7q36.1 hepatocellular carcinoma-associated antigen 112 ABP1 7q34-q36 amiloride binding protein 1 (amine oxidase (copper-containing)) KCNH2 7q35-q36 potassium voltage-gated channel, subfamily H (eag-related), member 2 NOS3 7q36 nitric oxide synthase 3 (endothelial cell) FLJ39415 7q36.1 hypothetical protein FLJ39415 ABCB8 7q35-q36 ATP-binding cassette, sub-family B (MDR/TAP), member 8 ACCN3 7q35 amiloride-sensitive cation channel 3, testis CDK5 7q36 cyclin-dependent kinase 5 SLC4A2 7q35-q36 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1) FASTK 7q35 FAST kinase C7orf21 7q36.1 chromosome 7 open reading frame 21 CENTG3 7q36.1£7q36.1 centaurin, gamma 3 LOC392152 7 similar to gastrulation brain homeobox 1 ASB10 7q35 ankyrin repeat and SOCS box-containing 10 LOC155046 7q36.1 similar to hypothetical protein 4931409K22 LOC346545 7q36.1 similar to hypothetical protein FLJ22527 ABCF2 7q35-q36 ATP-binding cassette, sub-family F (GCN20), member 2 CSGlcA-T 7q36.1 KIAA1402 protein SMARCD3 7q35-q36 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 NYREN18 7q36 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
27 - 4345 - 1203 - 2007 17785417
14 - 2546 - 629 - 2007 17785417
14 - 2386 - 614 - 2007 17785417
14 - 2040 - 596 - 2007 17785417
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestine  highly
 intestinesmall intestine  highly
Endocrineparathyroid   highly
Reproductivefemale systemplacenta  highly
 female systemovary  highly
Urinarykidney   highly
SystemCellPubmedSpeciesStageRna symbol
cell lineage
cell lines
IMPRINTING paternally
  • N terminal oxygenase domain, involved in dimerization
  • FAD binding domain
  • mono polymer homomer , dimer
    interspecies homolog to murine Nos3
    FAMILY NOS family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
  • myristoylated membrane anchor
  • translocation to mitochondria is regulated by the phosphorylation of NOS3 at Ser(617) and Ser(1179) by AKT1 and this is enhanced when AKT1 becomes nitrated at Tyr(350)
  • basic FUNCTION
  • catalyzing the synthesis of NO from l-arginine
  • plays an important role in adiponectin synthesis in adipocytes by increasing mitochondrial biogenesis and enhancing mitochondrial function
  • novel and important role of NOS3 in chondrocyte proliferation and endochondral bone growth and loss of NOS3 results in premature cell cycle exit and prehypertrophic chondrocyte differentiation during cartilage development
  • NOS3 and ADH5 play an important role in endothelial cell–mediated postnatal angiogenesis and vascular tone
  • is a pressure-dependent regulator of intraocular pressure
  • role for NOS3 in bone growth and metabolism and therefore its contribution may at least in part occur during early skeletal development
  • both NOS3 in the mother and the conceptus contribute to uteroplacental vascular changes and increased uterine arterial blood flow in normal pregnancy
  • enzyme responsible for synthesis of nitric-oxide (NO) in the vasculature
    signaling signal transduction
    a component
    small molecule metal binding,
    calcium Ca2+
  • binding the heme moiety of soluble guanylate cyclase forming a metal-nitrosyl adduct that is activated to catalyze the conversion of GTP to LGMP
  • RPA1, repressor of NOS3 associated with the development of coronary artery
  • calmodulin
  • PRKCZ binds and phosphorylates MAPK7, thereby decreasing NOS3 protein stability and contributing to early events of atherosclerosis
  • controls the expression of the angiogenesis inhibitor thrombospondin 2
  • JNK2 is a physiological kinase responsible for NOS3-Ser(116) phosphorylation and regulates NO production
  • GIT1 plays an important role in NOS3 function, in both normal and abnormal pathophysiologic states
  • GIT1 might regulate NOS3 activity in sinusoidal endothelial cells
  • activation of NOS3 promotes SRC-dependent CAV1-Tyr-14 phosphorylation and NOS3/CAV1 binding, that is, NOS3 feedback inhibition
  • VEGFA-mediated NOS3 phosphorylation on Ser1177 regulates angioblast and embryonic endothelial cells (EEC) division, which underlies the formation of blood vessels and vascular networks
  • UBIAD1 is a nonmitochondrial COQ10-forming enzyme with specific cardiovascular protective function via the modulation of NOS3 activity
  • HRAS mediates VEGFA-induced activation of endothelial nitric-oxide synthase (NOS3) and migratory response of human endothelial cells
  • neuronal NOS1 and endothelial NOS3 are constitutive calcium-dependent forms of the enzyme that regulate neural and vascular function respectively
  • cell & other
    Other regulated by SMAD2
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in squamous hyperplasia, dysplasia and squamous cell carcinoma of the head and neck
    constitutional   LOH    
    in atherosclerotic plaques
  • coronary spasm
  • placental abruption
  • putative susceptibility factor for late onset Alzheimer disease
  • to embryonic spina bifida
  • myocardial infarction, coronary spasm and preeclampsia
  • to Fabry disease with severe phenotype
  • to hypertension, pregnancy-induced
  • to hypertension resistant to conventional therapy
  • to limb deficiency defects in the presence of maternal smoking
  • to coronary artery disease (CAD)
  • to altered vascular function
  • Variant & Polymorphism SNP , other
  • G894T not likely to be involved in atherosclerosis
  • E298D variant in hypertension in pregnancy and in lower age at end stage renal disease in PKD1
  • Glu 298 ASP in fabry disease with severe phenotype
  • SNP increasing the risk of limb deficiency defects in the presence of maternal smoking
  • G894T associated to embryonic spina bifida
  • intron 4-VNTR and T-786C mutation enhance the inflammatory process in patients with chronic coronary artery disease
  • polymorphism 894G>T associated with increased CAD risk
  • subjects carrying the rs753482-C genotype express a novel stable truncated form of NOS3 with altered enzymatic activity that influences endothelial function, and associated with altered vascular function
  • Candidate gene
    Therapy target
    both SRC and NOS3 inhibition may be important therapeutic targets to prevent or limit vascular inflammation
  • mice deficient in endothelial NO synthase (Nos3-/-) show reduced VEGFA-induced mobilization of bone marrow progenitor cells to sites of injury