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FLASH GENE

Symbol

NOS3

contributors: mct - updated : 03-02-2015

HGNC name	nitric oxide synthase 3 (endothelial cell)
HGNC id	7876

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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
EC.number	1.14.13.39

DNA

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000603 27 - 4345 NP_000594 - 1203 - 2007 17785417 NM_001160111 14 - 2546 NP_001153583 - 629 - 2007 17785417 NM_001160110 14 - 2386 NP_001153582 - 614 - 2007 17785417 NM_001160109 14 - 2040 NP_001153581 - 596 - 2007 17785417

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine     highly   intestine small intestine     highly Endocrine parathyroid       highly Reproductive female system placenta     highly   female system ovary     highly Urinary kidney       highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Muscular myocyte

cell lineage

cell lines

fluid/secretion

at STAGE

IMPRINTING

paternally

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal oxygenase domain, involved in dimerization
	FAD binding domain

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Nos3

Homologene

FAMILY

NOS family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus
text	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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	calcium Ca2+

protein	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

REGULATION

Other

regulated by SMAD2

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in squamous hyperplasia, dysplasia and squamous cell carcinoma of the head and neck constitutional   LOH     in atherosclerotic plaques

Susceptibility

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
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   both SRC and NOS3 inhibition may be important therapeutic targets to prevent or limit vascular inflammation

ANIMAL & CELL MODELS

mice deficient in endothelial NO synthase (Nos3-/-) show reduced VEGFA-induced mobilization of bone marrow progenitor cells to sites of injury