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FLASH GENE
Symbol NRGN contributors: mct - updated : 10-03-2020
HGNC name neurogranin (protein kinase C substrate, RC3)
HGNC id 8000
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one collagen-like domain
  • one IQ domain
    • HOMOLOGY
    interspecies homolog to rattus Nrgn (96.2pc)
    homolog to murine Nrgn (96.2pc)
    Homologene
    FAMILY
  • neurogranin family
    • CATEGORY signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • in the cerebral cortex, found in the cell bodies of neurons in layers II-VI and in apical and basal dendrites of pyramidal neurons (not found in the dendrites in patients with Alzeihmer disease)
  • was first expressed and secreted by neuro-progenitors while the maximum was reached in mature cortical neurons
    • basic FUNCTION
  • postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium
  • target of thyroid hormone in brain
  • neuronal protein implicated in learning and memory
  • calcium/calmodulin binding protein, and proapoptotic factor
  • with PCP4, small IQ-motif calmodulin (CALM1)-binding proteins originally identified in the central nervous system (Kleerekoper 2009)
  • enhances post-synaptic sensitivity and increases synaptic strength in an activity- and NMDAR-dependent manner (Zhong 2009)
  • acts as a third messenger substrate for protein kinase C-mediated molecular cascades during synaptic development and remodeling
  • is the main postsynaptic protein regulating the availability of calmodulin-Ca(2+) in neurons
  • implicated in spatial learning and hippocampal plasticity
  • increased prefrontal cortex neurogranin enhances plasticity and extinction learning
  • NRGN-mediated enhancement of synaptic strength is due to its ability to target, rather than sequester, CALM1 within dendritic spines
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding calmodulin in the absence of calcium and enhancing synaptic strength (Zhong 2009)
  • NRGN is one of ZFP804A targets
  • FMR1 interacts with the 3'UTR of the NRGN mRNA and is required for activity-dependent translation of NRGN in the synaptic compartment and contextual memory formation
    • cell & other
    REGULATION
    Other expression modulated by thyroid hormones and retinoids (Ruano 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in patients with structural lesions resulting from mild traumatic brain injuries
    constitutional     --over  
    of GAP43 and neurogranin (NRGN) in CSF from ALzheimer disease patients
    constitutional     --over  
    in the AD patients than in cognitively healthy controls
    Susceptibility to schizophrenia
    Variant & Polymorphism SNP , other
  • polymorphism rs12807809 located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia
    • Candidate gene may have a role in neurocognitive and behavioral defects in the 11qter deletion disorder DEL11QD (Coldren 2009)
    Marker
  • NRGN and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD
    • Therapy target
    ANIMAL & CELL MODELS