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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
Location 12q24.22      Physical location : 117.650.978 - 117.799.582
Synonym name
  • neuronal NOS
  • NOS type I
  • neuronal nitric oxide synthase
  • Synonym symbol(s) NOS, NNOS, IHPS1, NC-NOS, bNOS, nNOS
    EC.number 1.14.13.39
    DNA
    TYPE functioning gene
    STRUCTURE 153.66 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure untranslated region of exon 2 exerting promoter and enhancer functions as well, facilitated in large part by cooperative interaction of two conserved adjacent CREB/AP-1 binding sites
    MAPPING cloned Y linked   status confirmed
    Map cen - PAH - IGF1 - ASCL1 - NFYB - TRA1 - DAO ,NOS1 - qter
    Authors Renault (94)
    Physical map
    TBX5 12q24.1 T-box 5 LOC387886 12 LOC387886 LOC390361 12 similar to microtubule-associated proteins 1A/1B light chain 3 LOC386654 12q24.1-q24.2 OSTF1 pseudogene TBX3 12q24.1 T-box 3 (ulnar mammary syndrome) LOC387887 12 LOC387887 KIAA1025 LOC387888 12 LOC387888 FLJ21415 12q24.22 hypothetical protein FLJ21415 FLJ14627 12q24.22-q24.23 hypothetical protein FLJ14627 HRK 12q24.23 harakiri, BCL2 interacting protein (contains only BH3 domain) FBXW8 12q24.21 F-box and WD-40 domain protein 8 TSC 12q24.23 hypothetical protein FLJ20607 FBXO21 12q24.21 F-box only protein 21 NOS1 12q24.2-q24.31 nitric oxide synthase 1 (neuronal) KSR2 12q24.23 kinase suppressor of Ras-2 RFC5 12q24.2-q24.3 replication factor C (activator 1) 5, 36.5kDa WSB2 12q24.23 WD repeat and SOCS box containing protein 2 FLJ20674 12q24.23 hypothetical protein FLJ20674 PBP 12q24.23 prostatic binding protein JIK 12q24.2 prostatic binding protein SDS3 12q24.23 likely ortholog of mouse Sds3 LOC144747 12q24.23 hypothetical protein LOC144747 H11 LOC387889 12 hypothetical gene supported by U41745; NM_014891 MGC39827 12q24.23 hypothetical protein MGC39827 LOC387890 12 similar to hypothetical protein C130069F04 PRKAB1 12q24.1-q24.3 protein kinase, AMP-activated, beta 1 non-catalytic subunit CIT 12q24.2 citron (rho-interacting, serine/threonine kinase 21) LOC92558 12q24.31 hypothetical protein LOC92558 RAB35 12q24.31 RAB35, member RAS oncogene family GCN1L1 12q24.3 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) RPLP0 12q24.2 ribosomal protein, large, P0 PXN 12q24 paxillin FLJ23042 12q24.31 hypothetical protein FLJ23042 LOC283458 12q24.31 nucleoside diphosphate kinase B-like pseudogene
    RNA
    TRANSCRIPTS type messenger
    text eleven distinct first-exons (exon 1a to 1k) transcripts via alternative promoter usage alternative splicing, cassette insertions/deletions and varied sites for 3'utr cleavage and polyadenylation (an isoform PNNOS involved in control of the tone of urethra, prostate, bladder
  • eleven of the twelve known exon 1 variants are expressed in a tissue- and stimulus-dependent manner
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 12189 161 1434 - 2018 30028847
  • nNOS
  • 30 splicing 12291 - 1468 - 2018 30028847
  • nNOSmu
  • differentially regulate myofilament function, but not baseline calcium handling in papillary muscles
  • 28 splicing 10776 - 1098 specifically expressed in the testis 2018 30028847
  • TnNOSb, nNOSgamma
  • differentially regulate myofilament function, but not baseline calcium handling in papillary muscles
  • 28 splicing 10781 - 1098 specifically expressed in the testis 2018 30028847
  • TnNOS
  • differentially regulate myofilament function, but not baseline calcium handling in papillary muscles
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue   
    Nervousbrain     Homo sapiens
    Reproductivefemale systemovary   
    Respiratoryrespiratory tractbronchiole    Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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 ĚNO 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    miscelleaneoussenescence 
    expression of a muscle-specific NOS1 transgene restores calpain S-nitrosylation in aging muscle and prevents sarcopenia
    miscelleaneouspain 
    blocking NOS1 signaling in the periphery may thus be a novel therapeutic strategy for the treatment of neuropathic pain
    ANIMAL & CELL MODELS