Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NOS1AP contributors: mct/npt/pgu - updated : 20-08-2012
HGNC name nitric oxide synthase 1 (neuronal) adaptor protein
HGNC id 16859
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, DEXRAS1
  • C-terminal PDZ-binding domain mediating interactions with NOS1
  • one PID domain
  • HOMOLOGY
    interspecies homolog to murine Nos1ap
    Homologene
    FAMILY
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • localized NOS1AP to cardiomyocyte intercalated discs (IDs) (
  • NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells
  • basic FUNCTION
  • adaptor protein that interacts with neuronal nitric-oxide synthase
  • involved in signal transduction in the NMDA receptor system
  • involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1
  • regulator of neuronal nitric oxide synthase effected by forming a ternary complex with PSD95 and DEXRAS1
  • might play a proactive role in the process of inflammation by transferring from cytoplasm to the nucleus and through the NMDA-nNOS signal pathway
  • affects potentially cardiac electrical conductance and coupling and thereby regulates the QT interval through propagation defects
  • is potentially a major genetic regulator of QT interval variation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • associated with EPS15 and NOTCH1
  • with RASD1 form a ternary complex that enhances the ability of neuronal Nitric oxide synthase to activate RASD1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with synapsins I, II, and III through an N-terminal phosphotyrosine-binding domain interaction
  • interaction with RASD1, a brain-enriched member of the Ras family of small monomeric G proteins
  • interacts with NOS1 to accelerate cardiac repolarization by inhibition of L-type calcium channel
  • SCRIB-NOS1AP association is direct and is mediated through the phosphotyrosine-binding (PTB) domain of NOS1AP and the fourth PDZ domain of SCRIB
  • 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in cardiomyocytes leads to altered cellular electrophysiology
    Susceptibility
  • to schizophrenia (SCZD9)
  • to variation of the QT interval (cardiac repolarization)
  • to sudden cardiac death (SCD)
  • to sudden death in patients with coronary artery disease
  • to variation of QT interval
  • Variant & Polymorphism other
  • common variant (rs10494366T > G, G-allele frequency 38 p100) was identified and consistently associated with QT-interval variation
  • association between genetic variation within NOS1AP and SCD
  • rs12084280, and rs10918859 associated with increased risk of sudden death in patients with coronary artery disease
  • noncoding polymorphism (rs7539120) that maps within an enhancer of NOS1AP, affects cardiac function by increasing NOS1AP transcript expression, and is a major regulator of the QT interval
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS