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FLASH GENE

Symbol

NOS1

contributors: mct/npt - updated : 04-02-2019

HGNC name	nitric oxide synthase 1 (neuronal)
HGNC id	7872

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a PDZ domain in the N-terminal part of the neuronal isoform participating in protein-protein interaction, and responsible for targeting nnos to synaptic membranes in muscles, and a N-terminal oxidase domain
	a flavodoxin-like domain
	a C-terminal reductase domain

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

NOS family

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,intermed filament
	intracellular,nucleus,nucleoplasm
text	localisation of NOS1 at the proximal portion of cilia in airway epithelium
	can be found also in the nucleus

basic FUNCTION	involved in nitric oxide biosynthesis, electron transport, synaptic transmission, muscle contraction, cell-cell signaling
	has a distinct local role in the physiological regulation of microvascular tone (Seddon 2008)
	negatively regulates adult neurogenesis
	neural stem cells (NSCs)-derived NOS1 stimulates neurogenesis via activating telomerase
	potential anti-inflammatory role of endothelial NOS1 that can attenuate unopposed, proinflammatory cytokine actions
	NOS1 in the collecting duct (CD) is critical in the regulation of fluid-electrolyte balance (MID: 23608660)
	its independent and local regulation of NO levels is crucial for normal cilia function
	plays a critical role in regulating cardiomyocyte function
	fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response
	neuronal NOS1 and endothelial NOS3 are constitutive calcium-dependent forms of the enzyme that regulate neural and vascular function respectively
	NOS1 may be significant in the pathophysiology of human ischemic heart disease with a preservative role in maintaining myocardial homeostasis
	NOS1 plays a critical role in neuronal differentiation of hippocampal neural progenitor cells (NPCs)
	plays an important role in neurite outgrowth and may thus influence brain development, specifically white matter (WM) microstructure
	mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes
	is a key arginine metabolising enzyme in the brain, and NOS1-derived nitric oxide (NO) plays an important role in regulating glutamatergic neurotransmission

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	essential factor for the production of nitric oxide by nitric oxide synthase 1 (NOS1), major modulator of cardiac function, is the cofactor tetrahydrobiopterin (BH4)

protein	calmodulin binding protein, Ca2+ dependent
	interacts with NOS1AP (NOS1 accelerate cardiac repolarization by inhibition of L-type calcium channel) (Chang 2008)
	in neuronal tissues, NOS1AP acts as a C-terminal PDZ domain ligand to neuronal NOS1, probably regulating translocation of NOS1 between synaptic and postsynaptic structures
	role for HSP90AA1 in regulating NOS1 sub-cellular localization
	FMR1 regulates translation of neuronal nitric oxide synthase 1 (NOS1) in the developing human neocortex
	NOS1 regulates load-induced muscular hypertrophy by activating transient receptor potential cation channel, subfamily V, member 1 (TRPV1)
	NOS1 is phosphorylated in skeletal muscle in response to insulin and in association with increased NO production
	SNTA1 which resides in nuclei of myocytes, functions as the upstream mediator of nuclear NOS1 translocation and NOS1-dependent mitochondrial biogenesis
	plays a critical role in the inflammatory response by promoting the activity of NFKB1
	NOS1 is transported into the nucleus and interacted with SOX2 to form a NOS1-SOX2 complex in neurons at the early stage following glutamate stimulation
	neuronal differentiation is likely dependent on calcineurin-mediated activation of NOS1

cell & other

REGULATION

activated by

various cAMP-activating agents due to increased transcription of either exon 1f or exon 1g, in neuronal- and keratinocyte-like cells, respectively

inhibited by

Zn (Zn inhibits NOS1 that partially contributes to an increase in oxidative stress, which subsequently leads to the nigrostriatal dopaminergic neurodegeneration)

Phosphorylated by	RPS6KA1 (associates with and phosphorylates NOS1 on Ser847 following mitogen stimulation))
	PRKD1 (PRKD1 specifically phosphorylates NOS1 in the activatory residue Ser 1412, and this phosphorylation increases NOS1 activity and ·NO production in living cells)

Other	regulation of NOS1 phosphorylation and expression by oxidative stress
	ubiquitination of NOS1 in the calmodulin-binding site triggers proteasomal degradation of the protein

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in glial tumors, which was significantly correlated with histologic grade and proliferative potential(Tanriover 2008) constitutional     --over   in the intervertebral disk degeneration constitutional     --low   in muscle aging, loss of NOS1, the primary source of muscle NO

Susceptibility

to infantile pyloric stenosis and to asthma to enuresis

Variant & Polymorphism SNP	SNP in the exon 1C 84G/A increases the risk of infantile pyloric stenosis
	predominantly CC genotype may be associated with enuresis

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous senescence   expression of a muscle-specific NOS1 transgene restores calpain S-nitrosylation in aging muscle and prevents sarcopenia miscelleaneous pain   blocking NOS1 signaling in the periphery may thus be a novel therapeutic strategy for the treatment of neuropathic pain

ANIMAL & CELL MODELS