Affinage

NRGN

Neurogranin · UniProt Q92686

Length
78 aa
Mass
7.6 kDa
Annotated
2026-04-29
58 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NRGN (neurogranin/RC3) is a small, brain-enriched postsynaptic protein that functions as a Ca²⁺-sensitive calmodulin reservoir in dendritic spines, thereby setting bidirectional thresholds for long-term potentiation and depression in hippocampal circuits. In its unphosphorylated, reduced state, NRGN binds apo-calmodulin with high affinity and accelerates Ca²⁺ dissociation from calmodulin's C-terminal sites up to 60-fold; PKC phosphorylation at Ser36 or NMDA-receptor-driven nitric oxide–dependent intramolecular disulfide formation each abolish or reduce calmodulin binding, releasing calmodulin to activate downstream effectors including CaMKII and calcineurin (PP2B) (PMID:8080473, PMID:15262982, PMID:9880498, PMID:33032807). Knockout mice exhibit shifted frequency-response curves for synaptic plasticity, enhanced LTP, occluded LTD, and elevated basal Ca²⁺ in cortical neurons, directly demonstrating NRGN's role as a metaplasticity gate (PMID:12097504, PMID:12859333). NRGN transcription is directly regulated by thyroid hormone through an intronic DR4 thyroid hormone response element bound by T3R–RXR heterodimers, and NRGN additionally suppresses Ras–ERK1/2 signaling downstream of neurotrophin receptors (PMID:9886843, PMID:25547065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Identification of RC3/neurogranin as a novel brain-restricted 78-amino-acid protein established the existence of a neuron-specific molecule whose function was unknown.

    Evidence Northern blot, in situ hybridization, and Western blot in rat brain

    PMID:2231781

    Open questions at the time
    • No function or molecular interactions identified
    • Expression restricted to rodent brain — human relevance unconfirmed
  2. 1992 High

    Localization of RC3 to postsynaptic dendritic spines distinguished it from the presynaptic GAP-43 and pointed to a role in postsynaptic signaling.

    Evidence Immunohistochemistry, Golgi impregnation/gold toning, and correlative EM in neostriatal neurons

    PMID:1528865

    Open questions at the time
    • No binding partners or enzymatic activity identified
    • Localization restricted to striatum — hippocampal and cortical spine localization not yet shown
  3. 1993 High

    The core biochemical mechanism was established: RC3 binds apo-calmodulin stoichiometrically, and PKC phosphorylation at Ser36 or Ca²⁺ influx disrupts this interaction, defining RC3 as a regulated calmodulin sequestration device.

    Evidence In vitro PKC phosphorylation, gel filtration, fluorescence spectroscopy, and mutagenesis of Ser36

    PMID:8071370 PMID:8080473

    Open questions at the time
    • Physiological consequence of calmodulin release not demonstrated
    • Whether PKC phosphorylation occurs in vivo during synaptic activity unknown
  4. 1993 High

    Demonstration that thyroid hormone regulates RC3 expression in vivo linked this postsynaptic protein to endocrine-dependent brain maturation.

    Evidence Hypothyroidism/T4 replacement in rat, Northern and Western blots across brain regions

    PMID:8344193

    Open questions at the time
    • Mechanism of transcriptional regulation (cis-element, receptor) not identified
    • Functional consequence of hypothyroid-induced RC3 loss on synaptic plasticity unknown
  5. 1993 High

    Functional reconstitution in Xenopus oocytes demonstrated that RC3 enhances Ca²⁺-dependent signaling in a Ser36-phosphorylation-dependent manner, providing the first evidence of a physiological readout.

    Evidence Heterologous expression, electrophysiology with Ser36 mutagenesis and PKC inhibitor

    PMID:8293295

    Open questions at the time
    • Oocyte system may not recapitulate neuronal Ca²⁺ dynamics
    • Downstream effectors of phospho-RC3-mediated signaling unidentified
  6. 1995 High

    Structural analysis revealed that calmodulin stabilizes an amphiphilic α-helix in RC3 only in the absence of Ca²⁺, providing a biophysical basis for the Ca²⁺-switch mechanism.

    Evidence Circular dichroism spectroscopy with recombinant protein and mutagenesis

    PMID:7896819

    Open questions at the time
    • No high-resolution structure of the RC3–CaM complex
    • Whether helix formation occurs in the crowded dendritic spine environment unknown
  7. 1996 High

    Systematic mutagenesis demonstrated that phospho-RC3 stimulates IP3/DAG-dependent Ca²⁺ signaling independently of calmodulin binding, revealing a dual-mode signaling capacity.

    Evidence Xenopus oocyte expression with Ser36Asp, Ser36Ala/Gly, and Phe37Trp variants; serotonin-evoked currents

    PMID:8971810

    Open questions at the time
    • Molecular target of phospho-RC3 in the IP3/DAG pathway not identified
    • Relevance of this pathway to neuronal plasticity not tested
  8. 1997 High

    RC3 phosphorylation increases during LTP maintenance in an NMDA-receptor- and PKC-dependent manner, directly linking RC3 modification to synaptic plasticity.

    Evidence Hippocampal slice LTP, phospho-RC3 immunoblot, APV and H-7 pharmacology

    PMID:9138717

    Open questions at the time
    • Causal role of RC3 in LTP not yet shown (correlation only)
    • Whether phospho-RC3 acts by releasing calmodulin during LTP or by an independent mechanism unknown
  9. 1999 High

    Identification of an intronic DR4 thyroid hormone response element that binds T3R–RXR heterodimers resolved the mechanism of thyroid hormone regulation of NRGN transcription.

    Evidence DNase I footprinting, immunoprecipitation of DNA–protein complexes, reporter gene assays in transfected cells

    PMID:9886843

    Open questions at the time
    • Contribution of additional cis-elements (e.g., the silencer element) to regional specificity not fully resolved
    • In vivo chromatin occupancy not confirmed
  10. 1999 High

    Discovery that NMDA receptor activation drives NOS-dependent oxidation of RC3, forming an intramolecular disulfide that reduces both PKC phosphorylation and CaM binding, established a redox-based signaling layer.

    Evidence Rat brain slice pharmacology with APV and NOS inhibitors, non-reducing SDS-PAGE, Western blot

    PMID:9880498

    Open questions at the time
    • Identity of the specific cysteine pair forming the disulfide not determined
    • Relative contribution of oxidation versus phosphorylation during plasticity unknown
  11. 2000 High

    Quantitative comparison of all modification states showed a hierarchy of CaM affinity (unmodified > glutathiolated > oxidized > phosphorylated), and that glutathiolation preferentially impairs PKC phosphorylation while preserving CaM binding, distinguishing it functionally from oxidation.

    Evidence CD spectroscopy, sedimentation equilibrium, CaM affinity chromatography with Cys-to-Gly/Ser mutants; mass spectrometry-based modification mapping

    PMID:10852729 PMID:11060308

    Open questions at the time
    • Relative abundance of each modification state in vivo during plasticity not quantified
    • Whether multiple modifications coexist on a single molecule in neurons unknown
  12. 2002 High

    Genetic knockout established RC3 as a causal metaplasticity gate: loss of RC3 shifts the frequency–response curve for LTP/LTD, confirming that RC3 controls the sliding threshold for bidirectional plasticity via CaMKII phosphorylation.

    Evidence Homologous recombination knockout mouse, hippocampal slice electrophysiology, mGluR pharmacology, phospho-CaMKII immunostaining

    PMID:12097504

    Open questions at the time
    • Behavioral consequences in learning and memory tasks not characterized in this study
    • Whether compensatory mechanisms partially mask RC3 loss unknown
  13. 2003 High

    RC3 knockout neurons showed elevated baseline Ca²⁺ and enhanced Ca²⁺ responses to NMDA and mGluR stimulation, directly confirming that RC3 dampens Ca²⁺ signaling in intact neurons.

    Evidence RC3 knockout cortical neuron cultures, fura-2 Ca²⁺ imaging, NMDA and mGluR agonist pharmacology

    PMID:12859333

    Open questions at the time
    • Whether Ca²⁺ dysregulation underlies the electrophysiological plasticity phenotype not directly tested
    • Contribution of individual Ca²⁺ sources (ER stores vs. influx) not dissected
  14. 2004 High

    Kinetic reconstitution showed that RC3 accelerates Ca²⁺ dissociation from CaM's C-terminal sites up to 60-fold — opposing CaMKII's slowing of dissociation — revealing the biophysical mechanism by which RC3 lowers effective CaM–Ca²⁺ affinity.

    Evidence Stopped-flow fluorescence kinetics with purified CaM, RC3, and CaMKII

    PMID:15262982

    Open questions at the time
    • Whether these kinetic parameters apply in the crowded dendritic spine milieu unknown
    • No structural explanation for how RC3 binding accelerates Ca²⁺ off-rate
  15. 2014 Medium

    Discovery that RC3 interacts with Ras and suppresses Ras–ERK1/2 signaling expanded its function beyond calmodulin regulation to growth factor signaling.

    Evidence Co-immunoprecipitation, Ras activity assay, ERK phosphorylation, neurite outgrowth, and RNAi in hippocampal neurons

    PMID:25547065

    Open questions at the time
    • Whether the Ras interaction is direct or calmodulin-mediated not fully resolved
    • Structural basis of RC3–Ras interaction unknown
    • Independent replication in a second laboratory lacking
  16. 2020 High

    Phosphoproteomic and electrophysiological analysis placed RC3 upstream of calcineurin (PP2B)-mediated dephosphorylation of NMDA receptor subunit GluN2A, explaining how RC3 levels control NMDA receptor current kinetics and LTP.

    Evidence Virus-mediated NRGN manipulation, quantitative phosphoproteomics, patch clamp, PP2B inhibitor rescue

    PMID:33032807

    Open questions at the time
    • Whether other CaM-dependent phosphatases contribute in parallel unknown
    • Phosphoproteomic changes not validated by site-directed mutagenesis of individual substrates

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key remaining questions include the high-resolution structure of the RC3–CaM complex, the quantitative balance of oxidation versus phosphorylation during plasticity in vivo, and whether the Ras interaction operates independently of calmodulin sequestration.
  • No atomic-resolution structure of full-length RC3 or RC3–CaM complex
  • In vivo stoichiometry of RC3 modifications during LTP/LTD not measured
  • Behavioral consequences of RC3 loss in cognitive tasks incompletely characterized in the primary mechanistic literature

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140313 molecular sequestering activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 1
Partners
CALM1CAMK2AGRIN2AKRASPPP3CAPRKCAPRKCG

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 RC3/neurogranin encodes a novel 78 amino acid protein enriched in rat brain, with restricted expression in neuronal subsets of cortex, striatum, and hippocampus, as demonstrated by Northern blot and in situ hybridization. Northern blot, in situ hybridization, Western blot with peptide antiserum Journal of neuroscience research High 2231781
1992 RC3/neurogranin accumulates postsynaptically in dendritic spines of neostriatal neurons, as established by immunohistochemistry, Golgi impregnation/gold toning, and correlative light/electron microscopy, distinguishing it from the presynaptic GAP-43. Immunohistochemistry, Golgi impregnation/gold toning, correlative light/electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 1528865
1993 RC3/neurogranin is a heat- and acid-stable protein kinase C substrate; PKC alpha, beta, or gamma phosphorylates a single site Ser36 adjacent to the calmodulin-binding domain; phosphorylation inhibits calmodulin binding; and RC3 forms a stoichiometric complex with calmodulin in the absence of Ca2+, which is disrupted by Ca2+ or PKC phosphorylation. Protein purification, in vitro PKC phosphorylation assay, gel filtration chromatography, fluorescence spectroscopy, immunoblot Archives of biochemistry and biophysics High 8080473
1993 RC3/neurogranin expression is regulated by thyroid hormone in the developing and adult rat brain; hypothyroidism reduces RC3 mRNA and protein in cortex, striatum, and hippocampus, and T4 treatment restores expression, whereas GAP-43 is unaffected. Slot blot, Northern blot, immunoblot, thyroidectomy and T4 replacement model Endocrinology High 8344193
1993 RC3/neurogranin, when expressed in Xenopus oocytes, enhances acetylcholine-evoked intracellular Ca2+-dependent Cl- currents 2-3 fold; this effect requires PKC phosphorylation at Ser36 and is blocked by PKC inhibitor H-7 or Ser36→Gly substitution; PKC-phosphorylated RC3 can also stimulate Ca2+ mobilization independently of IP3. Heterologous expression in Xenopus oocytes, electrophysiology, site-directed mutagenesis, pharmacological inhibition Brain research High 8293295
1994 RC3/neurogranin binds calmodulin preferentially when Ca2+ is absent (apo-CaM); addition of a negative charge at residue 36 (Ser36→Asp, mimicking PKC phosphorylation) is sufficient to abolish all detectable RC3-CaM interaction; the RC3-CaM interaction is bimodal with both ionic and hydrophobic components. Recombinant protein expression, site-directed mutagenesis, competitive fluorescence assay, calmodulin affinity chromatography The Journal of biological chemistry High 8071370
1994 RC3/neurogranin is predominantly a cytosolic protein but is found in lower amounts in membrane-enriched microsomes and synaptosomes, and is only loosely associated with the postsynaptic density. Subcellular fractionation, Western immunoblotting, synaptosome solubilization Brain research. Molecular brain research Medium 7898318
1994 The Ser36 residue of RC3/neurogranin is the PKC phosphorylation site; Ser36 variants fail to serve as PKC substrates; RC3 and GAP-43 show different affinity modes with calmodulin. Recombinant expression, site-directed mutagenesis, calmodulin-Sepharose affinity chromatography, in vitro PKC phosphorylation Journal of molecular neuroscience High 7654517
1994 The RC3/neurogranin promoter contains retinoic acid and glucocorticoid receptor response elements that confer hormone-regulated transcriptional activity in transfected cells; no thyroid hormone responsive element was found within the 2.4 kb upstream region. Genomic sequencing, promoter-reporter transfection, electrophoretic mobility shift assay, COS-7 and neuroblastoma cell transfection Brain research. Molecular brain research Medium 7898304
1995 Calmodulin stabilizes a basic amphiphilic alpha-helix within RC3/neurogranin and GAP-43 only when Ca2+ is absent; this structural interaction is disrupted by Ca2+ or PKC-mediated phosphorylation, providing a Ca2+-sensitive allosteric regulatory mechanism. Circular dichroism spectroscopy, recombinant protein expression, site-directed mutagenesis, overlapping peptide analysis The Journal of biological chemistry High 7896819
1995 The RC3/neurogranin gene spans ~13 kb with four exons; the promoter lacks TATA, GC, and CCAAT boxes but contains AP2 and SP1 binding sites; transcription is stimulated by phorbol ester (PMA) through PKC alpha, beta, gamma, delta, and epsilon (but not zeta); a 20-kDa AT-rich DNA-binding protein from rat brain binds shared regulatory sequences in both Ng/RC3 and PKCgamma promoters. Genomic sequencing, promoter deletion/reporter transfection, PKC isoform co-transfection, protein purification and gel mobility shift The Journal of biological chemistry High 7730337
1996 RC3/neurogranin mRNA expression is regulated by thyroid hormone in a cell-type-specific manner in the rat brain; hypothyroidism alters expression in specific layers of cortex, dentate gyrus, and caudate-putamen but not others; T3 induces RC3 transcription in hypothalamic GT1-7 cells within 6 hours, independent of new protein synthesis, indicating direct transcriptional regulation through nuclear T3 receptors. In situ hybridization, thyroid hormone manipulation, GT1-7 cell culture, nuclear T3 binding assay, reporter transfection, transcription inhibition Endocrinology / Journal of neurochemistry High 8603571 9282911
1997 RC3/neurogranin mRNA is translocated to apical dendrites of pyramidal neurons in human neocortex, and this dendritic targeting is lost in Alzheimer's disease but preserved in fronto-temporal dementia, indicating dependence on synapse integrity. Digoxigenin in situ hybridization in human postmortem tissue, comparative disease analysis Journal of neuropathology and experimental neurology Medium 9329454
1997 RC3/neurogranin phosphorylation at the postsynaptic compartment is increased during the maintenance phase of LTP in hippocampal slices; this increase is NMDA receptor-dependent and requires ongoing protein kinase activity, as H-7 application after LTP induction reverses the phosphorylation increase. Hippocampal slice LTP induction, immunoblot for phospho-RC3, NMDA receptor antagonist and PKC inhibitor pharmacology Brain research High 9138717
1999 The human NRGN gene contains a thyroid hormone-responsive element (sequence GGATTAAATGAGGTAA, a DR4-type element) located in the first intron ~3000 bp downstream of the transcription start site; this element binds T3R-RXR heterodimers but not T3R monomers or homodimers, and confers T3-dependent transcriptional regulation when fused to reporter promoters. Immunoprecipitation of DNA-protein complexes, DNase I footprinting, reporter gene transfection Endocrinology High 9886843
1999 NMDA receptor stimulation induces rapid and transient oxidation of neurogranin/RC3 in rat brain slices via nitric oxide synthase; this oxidation forms an intramolecular disulfide bond, reduces PKC phosphorylation efficiency, and decreases calmodulin binding affinity; the oxidation is blocked by NMDA receptor antagonist APV and NOS inhibitors. Rat brain slice pharmacology, non-reducing SDS-PAGE, Western blot, NOS inhibitors, dithiothreitol reduction The Journal of biological chemistry High 9880498
2000 Glutathione disulfide S-oxide (GS(O)SG), generated from S-nitrosoglutathione, glutathiolates neurogranin/RC3 at all four cysteine residues; glutathiolated RC3 is a poorer PKC substrate but retains normal calmodulin binding affinity, distinguishing it from oxidized (intramolecular disulfide) RC3; glutathiolation of RC3 occurs in rat brain slices under oxidative stress. In vitro chemical modification, mass spectrometry (implied), PKC phosphorylation assay, calmodulin binding assay, [35S]cysteine-labeled brain slice immunoprecipitation The Journal of biological chemistry High 11060308
2000 HMG-I (high-mobility group protein) binds AT-rich sequences in the RC3/neurogranin and PKCgamma promoters; PKC phosphorylation of HMG-I at Ser44 and Ser64 reduces its DNA-binding affinity 28-fold, providing a feedback regulatory mechanism for RC3 transcription. Protein purification, in vitro PKC phosphorylation, DNA binding assays, footprinting Journal of neurochemistry High 10617144
2000 Modified forms of neurogranin/RC3 show differential calmodulin binding: Cys(-)-NG > reduced-NG, glutathiolated-NG > oxidized-NG > phosphorylated-NG; both intramolecular disulfide formation and PKC phosphorylation reduce calmodulin affinity, with CD spectroscopy showing that only unmodified and glutathiolated forms increase alpha-helicity upon CaM binding. Circular dichroism spectroscopy, sedimentation equilibrium, calmodulin affinity chromatography, Cys-to-Gly/Ser mutagenesis Biochemistry High 10852729
2002 Knockout of RC3/neurogranin in mice causes lower phospho-CaMKII immunoreactivity, depressed basal excitatory synaptic transmission in CA1, enhanced LTP, occluded mGluR-dependent depression, shifted frequency-response curve, inability to induce LTD without prior high-frequency priming, and more robust depotentiation; this reveals a calmodulin-based sliding threshold mechanism for metaplasticity governed by RC3 and CaMKII phosphorylation states. Homologous recombination knockout, hippocampal slice electrophysiology, immunohistochemistry, mGluR pharmacology The Journal of neuroscience High 12097504
2003 RC3/neurogranin is induced in IL-2-deprived T cells; ectopic RC3 expression elevates intracellular Ca2+ and induces apoptosis even in the presence of IL-2; Ca2+ chelation (BAPTA-AM) blocks RC3-induced apoptosis; RC3 mutants unable to bind calmodulin fail to raise intracellular Ca2+ or induce apoptosis, indicating that RC3 drives apoptosis through a calmodulin-dependent Ca2+ mechanism. Retroviral expression, Ca2+ imaging, flow cytometry (apoptosis), BAPTA-AM chelation, calmodulin-binding mutants Molecular and cellular biology High 12808095
2003 Cortical neurons from RC3 knockout mice show altered Ca2+ dynamics: elevated baseline Ca2+, abnormal spontaneous Ca2+ oscillations, and enhanced Ca2+ responses to NMDA and class I mGluR agonists, without changes in neuronal morphology or density. RC3 knockout mouse cortical neuron culture, fura-2 Ca2+ imaging, pharmacological dissection with NMDA and mGluR agonists The European journal of neuroscience High 12859333
2004 RC3/neurogranin decreases the affinity of calmodulin for Ca2+ by increasing the rate of Ca2+ dissociation from the C-terminal sites of calmodulin up to 60-fold while having little effect on Ca2+ association; this opposes the effect of CaMKII, which decreases Ca2+ dissociation rates; phospho-CaMKII is resistant to RC3-mediated acceleration of Ca2+ dissociation. Stopped-flow fluorescence kinetics, calmodulin Ca2+ binding assays, CaMKII autophosphorylation The Journal of biological chemistry High 15262982
1999 A cis-acting element (TTCCAAAATGG) in the NRGN gene binds a developmentally regulated nuclear protein and interferes with T3 receptor-mediated transactivation, potentially contributing to the regional specificity of thyroid hormone regulation. Electrophoretic mobility shift assay, reporter gene transfection, developmental expression analysis FEBS letters Medium 10618501
1996 RC3/neurogranin variants with Ser36→Ala, Ser36→Gly, or Phe37→Trp, which bind calmodulin but lack PKC phosphorylation, do not enhance serotonin-evoked Ca2+-dependent currents in Xenopus oocytes; the Ser36→Asp variant (mimicking phosphorylated RC3), which does not bind calmodulin, significantly enhances currents like wild-type, indicating that PKC-phosphorylated RC3 stimulates G-protein-coupled IP3/DAG pathways independently of calmodulin binding. Xenopus oocyte expression, electrophysiology, site-directed mutagenesis Neuroscience letters High 8971810
2014 RC3/neurogranin interacts with Ras and suppresses Ras-ERK1/2 signaling; RC3 reduces NGF-induced Ras activation and ERK1/2 phosphorylation and inhibits neurite outgrowth in PC12 cells; RC3 suppresses the affinity of Ras for the Raf-1 Ras-binding domain but does not affect already-activated Raf-1; RC3 knockdown in hippocampal neurons enhances BDNF-stimulated ERK1/2 and neurite outgrowth. Co-immunoprecipitation, Ras activity assay, ERK phosphorylation Western blot, neurite outgrowth assay, RNAi knockdown in hippocampal neurons Molecular and cellular biochemistry Medium 25547065
2020 Neurogranin (Ng/NRGN) bidirectionally modulates LTP in hippocampus; decreasing Ng levels alters phosphorylation of postsynaptic density proteins including NMDA receptor subunit GluN2A (Grin2A), leading to accelerated NMDA receptor current decay; this LTP impairment and accelerated current decay are rescued by blocking protein phosphatase PP2B (calcineurin), placing Ng upstream of PP2B-mediated phosphoregulation of synaptic proteins. Virus-mediated gene manipulation, spike timing-dependent plasticity LTP protocols, quantitative phosphoproteomics, planar patch clamp, PP2B pharmacological inhibition Biological psychiatry High 33032807

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 349 15498886
1997 RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. Molecular neurobiology 176 9396008
1990 Subtractive cDNA cloning of RC3, a rodent cortex-enriched mRNA encoding a novel 78 residue protein. Journal of neuroscience research 163 2231781
2000 Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain. Endocrinology 133 10614638
1992 Localization of the protein kinase C phosphorylation/calmodulin-binding substrate RC3 in dendritic spines of neostriatal neurons. Proceedings of the National Academy of Sciences of the United States of America 116 1528865
1996 Cell-specific effects of thyroid hormone on RC3/neurogranin expression in rat brain. Endocrinology 112 8603571
1993 Thyroid hormone regulation of RC3, a brain-specific gene encoding a protein kinase-C substrate. Endocrinology 92 8344193
1992 Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA. The Journal of clinical investigation 91 1379612
1993 Characterization of a 7.5-kDa protein kinase C substrate (RC3 protein, neurogranin) from rat brain. Archives of biochemistry and biophysics 89 8080473
1994 Mutational and biophysical studies suggest RC3/neurogranin regulates calmodulin availability. The Journal of biological chemistry 85 8071370
2002 Targeted disruption of RC3 reveals a calmodulin-based mechanism for regulating metaplasticity in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 12097504
2004 RC3/Neurogranin and Ca2+/calmodulin-dependent protein kinase II produce opposing effects on the affinity of calmodulin for calcium. The Journal of biological chemistry 80 15262982
1995 Calmodulin stabilizes an amphiphilic alpha-helix within RC3/neurogranin and GAP-43/neuromodulin only when Ca2+ is absent. The Journal of biological chemistry 80 7896819
1999 The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron. Endocrinology 73 9886843
2000 Glutathiolation of proteins by glutathione disulfide S-oxide derived from S-nitrosoglutathione. Modifications of rat brain neurogranin/RC3 and neuromodulin/GAP-43. The Journal of biological chemistry 70 11060308
1997 Enhanced phosphorylation of the postsynaptic protein kinase C substrate RC3/neurogranin during long-term potentiation. Brain research 64 9138717
1997 Transcriptional induction of RC3/neurogranin by thyroid hormone: differential neuronal sensitivity is not correlated with thyroid hormone receptor distribution in the brain. Brain research. Molecular brain research 62 9387861
1997 Dendritic translocation of RC3/neurogranin mRNA in normal aging, Alzheimer disease and fronto-temporal dementia. Journal of neuropathology and experimental neurology 55 9329454
1999 N-methyl-D-aspartate induces neurogranin/RC3 oxidation in rat brain slices. The Journal of biological chemistry 52 9880498
2000 Thyroid hormone of maternal origin regulates the expression of RC3/neurogranin mRNA in the fetal rat brain. Brain research. Molecular brain research 51 11042365
1995 Structure and regulation of the gene encoding the neuron-specific protein kinase C substrate neurogranin (RC3 protein). The Journal of biological chemistry 51 7730337
2000 Phosphorylation of HMG-I by protein kinase C attenuates its binding affinity to the promoter regions of protein kinase C gamma and neurogranin/RC3 genes. Journal of neurochemistry 50 10617144
1994 Characterization of the promoter region and flanking sequences of the neuron-specific gene RC3 (neurogranin). Brain research. Molecular brain research 45 7898304
1994 Localization of RC3 (neurogranin) in rat brain subcellular fractions. Brain research. Molecular brain research 42 7898318
1993 Functional consequences of expression of the neuron-specific, protein kinase C substrate RC3 (neurogranin) in Xenopus oocytes. Brain research 42 8293295
2000 Calcium-sensitive interaction between calmodulin and modified forms of rat brain neurogranin/RC3. Biochemistry 41 10852729
2020 Neurogranin, Encoded by the Schizophrenia Risk Gene NRGN, Bidirectionally Modulates Synaptic Plasticity via Calmodulin-Dependent Regulation of the Neuronal Phosphoproteome. Biological psychiatry 38 33032807
2019 NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries. Clinical neurology and neurosurgery 38 31234132
2010 Spatiotemporal regulation of multiple overlapping sense and novel natural antisense transcripts at the Nrgn and Camk2n1 gene loci during mouse cerebral corticogenesis. Cerebral cortex (New York, N.Y. : 1991) 35 20693275
2005 RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory cortex in normal and denervated monkeys. The Journal of comparative neurology 35 16304627
1997 Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN). Genomics 35 9143500
2020 LINC00641/miR-4262/NRGN axis confines cell proliferation in glioma. Cancer biology & therapy 29 32543324
2003 Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor. Molecular and cellular biology 29 12808095
2013 Influence of the NRGN gene on intellectual ability in schizophrenia. Journal of human genetics 28 23903071
1997 Thyroid hormone-regulated expression of RC3/neurogranin in the immortalized hypothalamic cell line GT1-7. Journal of neurochemistry 28 9282911
2012 Impact of the genome wide supported NRGN gene on anterior cingulate morphology in schizophrenia. PloS one 26 22253779
1995 RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism. Brain research. Molecular brain research 26 7539519
1994 Rapid purification, site-directed mutagenesis, and initial characterization of recombinant RC3/neurogranin. Journal of molecular neuroscience : MN 25 7654517
2019 Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia. BMC psychiatry 23 30953482
2000 Differential regulation of primary protein kinase C substrate (MARCKS, MLP, GAP-43, RC3) mRNAs in the hippocampus during kainic acid-induced seizures and synaptic reorganization. Journal of neuroscience research 21 11054811
2021 Brain CHID1 Expression Correlates with NRGN and CALB1 in Healthy Subjects and AD Patients. Cells 20 33924468
1996 Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the prenatal and adult caprine brain. Brain research. Molecular brain research 17 9013778
2021 LncRNA RBPMS-AS1 promotes NRGN transcription to enhance the radiosensitivity of glioblastoma through the microRNA-301a-3p/CAMTA1 axis. Translational oncology 15 34800915
2011 Analysis of neurogranin (NRGN) in schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 15 21538840
2010 A high-fat diet induces lower expression of retinoid receptors and their target genes GAP-43/neuromodulin and RC3/neurogranin in the rat brain. The British journal of nutrition 15 20102671
2003 Calcium dynamics are altered in cortical neurons lacking the calmodulin-binding protein RC3. The European journal of neuroscience 15 12859333
2002 Postnatal maternal separation elevates the expression of the postsynaptic protein kinase C substrate RC3, but not presynaptic GAP-43, in the developing rat hippocampus. Developmental neuroscience 15 12697986
2000 Pre- and postsynaptic localization of RC3/neurogranin in the adult rat spinal cord: an immunohistochemical study. Journal of neuroscience research 15 10700012
2009 Conservation and expression of IQ-domain-containing calpacitin gene products (neuromodulin/GAP-43, neurogranin/RC3) in the adult and developing oscine song control system. Developmental neurobiology 13 19023859
2006 The deconstruction of the Hy Scale of MMPI-2: failure of RC3 in measuring somatic symptom expression. Journal of personality assessment 12 16972822
2016 Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population. Journal of affective disorders 11 26828755
1999 Identification of a cis-acting element that interferes with thyroid hormone induction of the neurogranin (NRGN) gene. FEBS letters 11 10618501
1996 Functional studies of single-site variants in the calmodulin-binding domain of RC3/neurogranin in Xenopus oocytes. Neuroscience letters 9 8971810
2003 Environmental stress-induced extracellular isoperoxidase RC3 from rice. Journal of environmental biology 4 12974407
2014 RC3/neurogranin negatively regulates extracellular signal-regulated kinase pathway through its interaction with Ras. Molecular and cellular biochemistry 3 25547065
2026 Single-cell characterization of the adult male hippocampus suggests a prominent, and cell-type specific, role for Nrgn and Sgk1 in response to a social stressor. Molecular psychiatry 1 41554902
2023 Molecular Characterization of Neurogranin (NRGN) Gene from Red‑Bellied Pacu (Piaractus brachypomus). Molecular neurobiology 1 37922064
2016 Derivation of the human embryonic stem cell line RCe007-A (RC-3). Stem cell research 1 27346192