Affinage

NCS1

Neuronal calcium sensor 1 · UniProt P62166

Length
190 aa
Mass
21.9 kDa
Annotated
2026-04-29
74 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCS1 is a myristoylated, EF-hand calcium sensor that transduces local Ca²⁺ signals into regulation of vesicular trafficking, receptor desensitization, intracellular Ca²⁺ release, and G-protein signaling at neuronal and non-neuronal membranes. It binds two Ca²⁺ ions with strong positive cooperativity and undergoes conformational changes that govern partner selectivity: it stimulates PI4Kβ in a myristoylation-dependent manner to promote Golgi-derived vesicular trafficking and exocytosis (PMID:11526106, PMID:17555535); it associates with the D2 dopamine receptor to inhibit GRK2-mediated phosphorylation, thereby sustaining D2R surface expression and enhancing dopaminergic signaling, LTP, and spatial memory (PMID:12351722, PMID:19755107, PMID:41211723); and it binds the InsP3R suppressor domain (via its Leu-89 hydrophobic pocket) to increase channel open probability and ER-to-mitochondria Ca²⁺ transfer in a complex with WFS1 (PMID:31659121, PMID:30352948). NCS1 also negatively regulates G-protein signaling by trapping Ric-8A in a conformation refractory to CK2 phosphorylation and GEF activity, a mechanism elucidated by crystallography and confirmed to control synapse number in Drosophila (PMID:38018500, PMID:25074811, PMID:28119500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Establishing that NCS-1 is a bona fide Ca²⁺ sensor — it binds exactly two Ca²⁺ ions with strong cooperativity and undergoes conformational changes — defined the biophysical framework for all subsequent partner-interaction studies.

    Evidence Flow dialysis, equilibrium gel filtration, Trp fluorescence, and thiol-reactivity assays on purified NCS-1

    PMID:7806504

    Open questions at the time
    • Structural basis of cooperativity not resolved at atomic level in this study
    • Physiological relevance of Mg²⁺ competition in cells not tested
  2. 1996 High

    Demonstrating that NCS-1 can activate calmodulin-dependent enzymes (phosphodiesterase, calcineurin, NOS) established it as a functional Ca²⁺-effector protein distinct from calmodulin, not merely a passive Ca²⁺ buffer.

    Evidence In vitro enzyme activation assays with purified NCS-1, behavioral rescue of calmodulin-defective Paramecium

    PMID:8799187

    Open questions at the time
    • Whether these calmodulin-target activations occur in mammalian neurons in vivo remained untested
    • Structural basis for calmodulin-target recognition not determined
  3. 2001 High

    Identification of PI4Kβ as a direct, myristoylation-dependent binding partner of NCS-1 established the first defined molecular mechanism — Ca²⁺-dependent lipid kinase activation — by which NCS-1 regulates vesicular trafficking at the Golgi.

    Evidence Co-immunoprecipitation, in vitro kinase assay, myristoylation-defective mutant in COS-7 cells

    PMID:11526106

    Open questions at the time
    • Cargo specificity of NCS-1/PI4Kβ-driven trafficking unknown
    • Whether endogenous NCS-1 levels are limiting for PI4Kβ activity in neurons not tested
  4. 2002 High

    Discovery that NCS-1 attenuates D2 dopamine receptor internalization by reducing GRK2-mediated phosphorylation revealed a second major signaling axis — receptor desensitization control — mechanistically distinct from PI4Kβ regulation.

    Evidence Receptor internalization and cAMP assays in HEK293 cells, co-IP from striatal neurons, Ca²⁺-binding mutant

    PMID:12351722

    Open questions at the time
    • Direct GRK2 inhibition mechanism (competitive vs. allosteric) not defined
    • Generality to other GPCRs beyond D2R unclear
  5. 2002 High

    Showing that NCS-1 inhibits insulin-stimulated GLUT4 translocation through PI4Kβ extended NCS-1 function beyond neurons to metabolic regulation, and demonstrated pathway specificity via dominant-negative PI4K epistasis.

    Evidence GLUT4-EGFP translocation assay in 3T3-L1 adipocytes, dominant-negative PI4K co-transfection

    PMID:12011096

    Open questions at the time
    • Physiological relevance at endogenous NCS-1 levels in adipocytes not established
    • Mechanism by which PI4Kβ activation diverts GLUT4 trafficking not resolved
  6. 2007 Medium

    Visualization of NCS-1 interactions with specific ARF isoforms at distinct subcellular sites, with ARF1 selectively enhancing PI4Kβ-stimulated exocytosis, revealed combinatorial specificity within the NCS-1/ARF/PI4Kβ trafficking complex.

    Evidence Bimolecular fluorescence complementation in live HeLa cells, regulated exocytosis assay

    PMID:17555535

    Open questions at the time
    • Stoichiometry and order of assembly of the ternary complex unknown
    • Whether ARF-GEF activity is required for NCS-1/ARF interaction not tested
  7. 2008 High

    Establishing that NCS-1 binds PICK1's BAR domain in a Ca²⁺-dependent manner to mediate mGluR-LTD (but not NMDAR-LTD) defined NCS-1 as a synapse-type-specific plasticity regulator via a mechanism independent of D2R or PI4Kβ.

    Evidence Electrophysiological LTD recordings in perirhinal cortex, co-IP, peptide inhibition

    PMID:19109914

    Open questions at the time
    • Whether NCS-1/PICK1 interaction regulates AMPAR trafficking directly not shown
    • Relevance in other brain regions unknown
  8. 2009 High

    NCS-1 overexpression in dentate gyrus enhanced LTP and spatial memory through D2R interaction, directly linking NCS-1/D2R function to cognitive behavior and establishing D2R as the dominant NCS-1 effector for hippocampal plasticity.

    Evidence Inducible transgenic overexpression, LTP electrophysiology, behavioral assays, cell-permeant NCS-1/D2R disrupting peptide (DNIP)

    PMID:19755107

    Open questions at the time
    • Whether endogenous NCS-1 is necessary (loss-of-function) for these behaviors not tested in this study
    • Downstream signaling cascade from D2R to LTP machinery not mapped
  9. 2009 High

    Genetic epistasis in Drosophila demonstrated that NCS-1 (Frequenin) modulates Ca²⁺ entry through voltage-gated Ca²⁺ channels independently of PI4Kβ, resolving that NCS-1 has at least two independent effector axes for neurotransmitter release.

    Evidence Frequenin null mutant, trans-heterozygous epistasis with cacophony null, electrophysiology and Ca²⁺ imaging, PI4Kβ null rescue

    PMID:19861494

    Open questions at the time
    • Direct biochemical interaction with Cav α1 subunit not demonstrated
    • Whether this mechanism is conserved in mammals not established
  10. 2014 High

    Crystal structure of NCS-1 ortholog Frq2 and identification of Ric-8A as a Ca²⁺-dependent binding partner — where NCS-1 negatively regulates Ric-8A/Gαs signaling to control synapse number — opened a new effector axis linking NCS-1 to heterotrimeric G-protein signaling.

    Evidence X-ray crystallography, site-directed mutagenesis, co-IP, Drosophila genetic epistasis

    PMID:25074811

    Open questions at the time
    • Atomic details of the NCS-1/Ric-8A interface not yet resolved
    • Mammalian in vivo validation of synapse number regulation lacking
  11. 2017 High

    The NCS-1/FD44 co-crystal structure revealed that the mobile C-terminal helix H10 acts as a molecular switch: FD44 stabilizes H10 inside NCS-1's hydrophobic crevice, sterically blocking Ric-8A binding and rescuing synapse and learning deficits in a fragile X model.

    Evidence X-ray crystallography of NCS-1/FD44, binding assays, Drosophila behavioral and synapse assays

    PMID:28119500

    Open questions at the time
    • Pharmacokinetics and selectivity of FD44 in mammalian systems unknown
    • Whether H10 dynamics also gate D2R and PI4Kβ interactions not tested
  12. 2018 High

    Discovery that NCS-1, WFS1, and IP3R form a ternary complex at ER–mitochondria contact sites to promote Ca²⁺ transfer established NCS-1 as a regulator of organelle communication and mitochondrial function, with relevance to Wolfram syndrome.

    Evidence Co-IP, proximity ligation assay, Ca²⁺ transfer and mitochondrial function measurements, NCS-1 rescue in WFS1-null patient fibroblasts

    PMID:30352948

    Open questions at the time
    • Stoichiometry of the ternary complex undefined
    • Whether NCS-1 is directly recruited by WFS1 or indirectly via IP3R not resolved
  13. 2019 High

    Mapping the NCS-1 binding site to the InsP3R1 suppressor domain (residues 66–110) and identifying Leu-89 as the critical NCS-1 residue defined the structural basis by which NCS-1 increases IP3R channel open probability and Ca²⁺ signaling.

    Evidence Co-IP with blocking peptides, L89 mutagenesis, Ca²⁺ signaling and cell survival assays

    PMID:31659121

    Open questions at the time
    • High-resolution structure of NCS-1/InsP3R complex not obtained
    • Allosteric mechanism by which suppressor domain binding increases open probability unknown
  14. 2023 High

    High-resolution crystal structure of NCS-1 bound to Ric-8A revealed mutual exclusivity with Gα binding and showed NCS-1 traps Ric-8A in a CK2-phosphorylation-resistant conformation, fully explaining how NCS-1 inhibits Ric-8A GEF activity and how Ca²⁺ concentration reverses this inhibition.

    Evidence X-ray crystallography, reconstituted GEF and phosphorylation assays, biophysical binding measurements

    PMID:38018500

    Open questions at the time
    • In vivo validation of CK2-phosphorylation regulation of Ric-8A by NCS-1 in mammalian neurons not performed
    • Whether other NCS family members share this mechanism unknown
  15. 2025 High

    Demonstrating that NCS-1 promotes D2R exocytic trafficking to the plasma membrane and that FDA-approved drugs disrupt this by targeting NCS-1's D2R-binding site (perturbing C-terminal helix H10 dynamics) established a druggable mechanism for modulating dopamine signaling.

    Evidence In vitro binding, cellular D2R surface expression assays, FDA drug screen, X-ray crystallography of NCS-1/drug complexes

    PMID:41211723

    Open questions at the time
    • In vivo efficacy and selectivity of identified drugs for NCS-1/D2R disruption not tested
    • Whether H10 perturbation simultaneously affects Ric-8A and PI4Kβ interactions not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural model explaining how NCS-1 selects among its multiple effectors (PI4Kβ, D2R, InsP3R, Ric-8A, PICK1, TRPA1) as a function of Ca²⁺ concentration, membrane context, and C-terminal helix dynamics remains unresolved.
  • No mammalian loss-of-function genetic model has comprehensively assessed NCS-1 physiological roles
  • Structural basis for partner selectivity (overlapping vs. distinct binding surfaces) not fully mapped
  • Role of NCS-1 at ER-mitochondria contacts in neurodegeneration requires in vivo validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140299 molecular sensor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-382551 Transport of small molecules 2
Partners
ARF1DRD2ITPR1PICK1PIK4CBRIC8ATRPA1WFS1
Complex memberships
NCS-1/PI4Kβ/ARF1 trafficking complexNCS-1/Ric-8A signaling complexNCS-1/WFS1/IP3R ER-mitochondria complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 NCS-1 binds exactly two Ca2+ ions with strong positive cooperativity (Hill coefficient ~2) and two Mg2+ ions; Mg2+ competes with Ca2+ binding and shifts isotherms to higher Ca2+ concentrations. Ca2+ (and Mg2+) binding induces conformational changes detectable by Trp fluorescence and near-UV difference spectra, with the Mg2+-saturated form resembling the Ca2+-loaded form. Flow dialysis (Ca2+ binding), equilibrium gel filtration (Mg2+ binding), Trp fluorescence spectroscopy, near-UV difference spectra, DTNB thiol reactivity assay The Journal of biological chemistry High 7806504
1996 NCS-1 can directly activate calmodulin-dependent enzymes cyclic nucleotide phosphodiesterase and calcineurin in vitro, and co-activates nitric oxide synthase synergistically with calmodulin, demonstrating it can substitute for or potentiate calmodulin functions. In vitro enzyme activity assays (phosphodiesterase, calcineurin, NOS), injection into calmodulin-defective Paramecium (behavioral rescue), protein crystallization Proceedings of the National Academy of Sciences of the United States of America High 8799187
1999 NCS-1 localizes subcellularly to the trans-Golgi apparatus membranes and neurofilament-rich axonal structures in rat neurons, suggesting roles in Ca2+-regulated protein trafficking and cytoskeletal interactions. Light- and electron-microscopic immunohistochemistry, double-labeling with neurofilament antibodies Cell and tissue research Medium 10022960
2001 NCS-1 physically associates with phosphatidylinositol 4-kinase beta (PI4Kbeta) in a myristoylation-dependent manner and stimulates PI4Kbeta lipid kinase activity; this complex localizes to the Golgi and promotes vesicular trafficking in COS-7 cells. Co-immunoprecipitation, in vitro kinase assay with recombinant proteins, immunoprecipitation of PI4K activity from anti-NCS-1 precipitates, YFP co-localization, [32P]phosphate incorporation in permeabilized cells, myristoylation-defective mutant analysis The Journal of biological chemistry High 11526106
2002 NCS-1 attenuates agonist-induced D2 dopamine receptor internalization by reducing D2 receptor phosphorylation, thereby enhancing D2-mediated cAMP inhibition after dopamine stimulation; this effect requires Ca2+-binding capacity of NCS-1 and involves association with GRK2. Receptor internalization assay in HEK293 cells, cAMP measurement, co-immunoprecipitation from striatal neurons, NCS-1 Ca2+-binding mutant, colocalization by immunofluorescence The Journal of neuroscience High 12351722
2002 NCS-1 inhibits insulin-stimulated GLUT4 translocation in adipocytes through a PI4-kinase-dependent mechanism; co-expression of an inactive PI4-kinase mutant blocks this NCS-1 effect, while NCS-1 does not alter Akt/PKB phosphorylation or Cbl recruitment. Overexpression in 3T3L1 adipocytes, GLUT4-EGFP translocation assay, dominant-negative PI4-kinase co-transfection, colocalization microscopy The Journal of biological chemistry High 12011096
2003 NCS-1 (frequenin) co-localizes with Kv4.2 at the sarcolemma of neonatal mouse ventricular myocytes, consistent with a role as a Kv4 channel auxiliary/regulatory subunit in the heart. Immunoblot, immunocytochemical co-localization in isolated neonatal cardiomyocytes Pediatric research Low 12612193
2006 NCS-1 interacts in a Ca2+-dependent manner with ARF1, CAPS1, cyclic nucleotide phosphodiesterase, vacuolar ATPase, AP1/AP2 clathrin adaptors, and type I TGF-beta receptor; distinct binding partners were identified for NCS-1 versus hippocalcin or neurocalcin delta. GST pulldown from bovine brain cytosol and membrane fractions, MALDI-MS identification of bound proteins, Western blotting Proteomics Medium 16470652
2007 NCS-1 directly interacts with ARF isoforms 1, 3, 5, and 6 (but not equally with PI4Kbeta which preferentially binds ARF1/3) at distinct intracellular locations; ARF1 but not ARF5/6 enhances PI4Kbeta-stimulated exocytosis, suggesting specificity in the NCS-1/ARF/PI4Kbeta trafficking complex. Bimolecular fluorescence complementation (split fluorescent protein) in live HeLa cells, FRAP, regulated exocytosis assay Traffic (Copenhagen, Denmark) Medium 17555535
2008 NCS-1 mediates mGluR-LTD (but not NMDAR-LTD) in perirhinal cortex by binding directly to the BAR domain of PICK1 in a Ca2+-dependent manner; mGluR activation stimulates NCS-1/PICK1 association, and introduction of a PICK1 BAR domain fusion protein selectively blocks mGluR-LTD. Electrophysiology (LTD recording), co-immunoprecipitation, peptide inhibitor introduction, pharmacological dissection Neuron High 19109914
2008 NCS-1 differentially modulates voltage-gated Ca2+ channels in growth cones versus somata of regenerating Lymnaea neurons; a dominant-negative C-terminal NCS-1 peptide selectively reduces current density, slope conductance, and shifts reversal potential in growth cones but not somata. Whole-cell patch-clamp in growth cones and somata, dominant-negative peptide application The European journal of neuroscience Medium 18279316
2009 NCS-1 overexpression in the dentate gyrus enhances LTP at the medial perforant path and spatial memory acquisition; these effects require NCS-1 interaction with D2 receptors, as a cell-permeant peptide (DNIP) disrupting NCS-1/D2R binding reverses all phenotypes. Inducible transgenic overexpression, LTP electrophysiology, behavioral tests, cell-permeant inhibitory peptide (DNIP), D2R antagonist L-741,626 Neuron High 19755107
2009 mu-Calpain cleaves NCS-1 within the N-terminal pseudoEF-hand domain; loss of this domain markedly decreases NCS-1's Ca2+ affinity as measured by ITC, suggesting the pseudoEF-hand stabilizes the three functional EF-hands. In vitro mu-calpain proteolysis, N-terminal sequencing, MALDI mass spectrometry, isothermal titration calorimetry (ITC) Cell calcium High 19732951
2009 In Drosophila, Frequenin (NCS-1 ortholog) modulates Ca2+ entry through a functional interaction with the alpha1 subunit of voltage-gated Ca2+ channels (cacophony), regulating neurotransmitter release and nerve-terminal growth; this effect is independent of PI4Kbeta. Genetic null mutant generation (site-specific recombination), trans-heterozygous epistasis analysis with cacophony null, electrophysiology, Ca2+ imaging, PI4Kbeta null background rescue experiment Journal of cell science High 19861494
2010 Paclitaxel interacts with NCS-1 to increase NCS-1 expression, and NCS-1 in turn enhances InsP3R channel open probability, increasing spontaneous Ca2+ oscillation frequency in cardiomyocytes; shRNA knockdown of NCS-1 decreases InsP3R-dependent Ca2+ release. Live cell Ca2+ imaging in neonatal rat cardiomyocytes, shRNA knockdown, InsP3R inhibitor pharmacology, single-channel recording Journal of molecular and cellular cardiology High 20801127
2012 NCS-1 associates with adenosine A2A receptors and modulates A2A receptor downstream intracellular signaling in a Ca2+-dependent manner. Bioluminescence resonance energy transfer (BRET) in living cells, co-immunoprecipitation, downstream signaling assay Frontiers in molecular neuroscience Medium 22529776
2014 Drosophila Ric8a binds to Frq2 (NCS-1 ortholog) but not Frq1; human NCS-1 and Ric8a reproduce this binding with the same structural requirements at positions R94 and T138. The Frq2-Ric8a-Gαs pathway regulates synapse number (Frq2 negatively regulates Ric8a), while Ric8a's regulation of neurotransmitter release is independent of Frq2 binding. Crystallographic structure of Frq2, site-directed mutagenesis, co-immunoprecipitation, Drosophila genetics (overexpression/loss-of-function), electrophysiology Journal of cell science High 25074811
2014 In substantia nigra dopamine neurons, Cav1.3 L-type Ca2+ channel activity controls D2-autoreceptor desensitization through NCS-1; pharmacological or genetic disruption of Cav1.3 activity or NCS-1/D2R interaction prevents the maturation of non-desensitizing D2-autoreceptor responses. Electrophysiology in acute brain slices, pharmacological blockade, Cav1.3 knockout mice, l-DOPA/cocaine in vivo treatments, mRNA quantification Brain : a journal of neurology High 24934288
2017 The crystal structure of NCS-1 bound to the small molecule FD44 reveals that FD44 stabilizes a mobile C-terminal helix inside a hydrophobic crevice of NCS-1, thereby sterically blocking Ric8a interaction; FD44 disrupts NCS-1/Ric8a binding and restores normal synapse number and associative learning in a Drosophila fragile X model. X-ray crystallography of NCS-1/FD44 complex, virtual screening, co-immunoprecipitation/binding assay, Drosophila behavioral and synapse assays, structure-activity relationship with analogs Proceedings of the National Academy of Sciences of the United States of America High 28119500
2018 NCS-1 forms a complex with WFS1 and IP3R to promote Ca2+ transfer from the ER to mitochondria; NCS-1 abundance is reduced in WFS1-null fibroblasts, and NCS-1 overexpression restores ER-mitochondria interactions, Ca2+ exchange, and mitochondrial function in these cells. Co-immunoprecipitation, proximity ligation assay (ER-mitochondria contacts), Ca2+ transfer measurements, mitochondrial function assays, NCS-1 overexpression rescue in patient fibroblasts Science signaling High 30352948
2019 NCS-1 binds to residues 66-110 on the suppressor domain of InsP3R1; Leu-89 in the hydrophobic pocket of NCS-1 is critical for this interaction; NCS-1/InsP3R1 binding increases InsP3R channel open probability and intracellular Ca2+ signaling, and Leu-89 variants reduce Ca2+ signaling and cell survival. Protein docking, co-immunoprecipitation with blocking peptides, site-directed mutagenesis (L89 variants), Ca2+ signaling assays, cell survival assay The Journal of biological chemistry High 31659121
2023 NCS-1 binding to Ric-8A is mutually exclusive with Gα binding; NCS-1 induces a structural rearrangement in Ric-8A that traps it in a conformation inaccessible to casein kinase II phosphorylation, thereby inhibiting Ric-8A GEF activity toward Gα; increasing Ca2+ concentration restores nucleotide exchange activity. Reconstitution of NCS-1/Ric-8A complexes, X-ray crystallography (high-resolution structure of NCS-1/Ric-8A interface), GEF activity assay, phosphorylation assays, biophysical binding experiments eLife High 38018500
2024 NCS-1 physically and functionally interacts with TRPA1 channel; NCS-1 enhances TRPA1-dependent Ca2+ influx, current density, open probability, and conductance through a PI3K-dependent pathway; NCS-1 and TRPA1 co-immunoprecipitate. Co-immunoprecipitation, Ca2+ imaging (Fura-2), whole-cell and single-channel electrophysiology, PI3K inhibitor pharmacology, qRT-PCR, Western blot in breast cancer and neuroblastoma cells Journal of physiology and biochemistry Medium 38564162
2025 NCS-1 promotes D2R trafficking to the plasma membrane via active exocytosis in a Ca2+-dependent manner; FDA-approved drugs azilsartan medoxomil, atorvastatin, and vilazodone disrupt the NCS-1/D2R interaction by targeting NCS-1's D2R binding site, reducing D2R surface expression; structural studies reveal these compounds perturb the regulatory C-terminal helix H10 dynamics. In vitro binding assays, cellular D2R trafficking/surface expression assays, FDA drug screen, X-ray crystallography of NCS-1/drug complexes, molecular dynamics Journal of medicinal chemistry High 41211723
2015 NCS-1 membrane binding is favored by phospholipids with phosphoethanolamine headgroups and unsaturated acyl chains; the N-terminal peptide of NCS-1 contains two amphiphilic helices that mediate membrane interaction; Ca2+ binding causes conformational change that reshuffles NCS-1 orientation at the membrane; myristoylation does not function as a classical Ca2+-myristoyl switch but may serve a structural folding role. Langmuir lipid monolayer pressure measurements with purified protein, myristoylated and unmyristoylated NCS-1 comparison Colloids and surfaces. B, Biointerfaces Medium 26705828

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 178 12351722
2002 Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients. Proceedings of the National Academy of Sciences of the United States of America 172 12496348
2009 NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory. Neuron 161 19755107
2001 Interaction of neuronal calcium sensor-1 (NCS-1) with phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and affects membrane trafficking in COS-7 cells. The Journal of biological chemistry 131 11526106
2018 ER-mitochondria cross-talk is regulated by the Ca2+ sensor NCS1 and is impaired in Wolfram syndrome. Science signaling 113 30352948
2014 Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons. Brain : a journal of neurology 100 24934288
1996 Direct modulation of calmodulin targets by the neuronal calcium sensor NCS-1. Proceedings of the National Academy of Sciences of the United States of America 97 8799187
2008 Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1. Neuron 91 19109914
1994 Cation binding and conformational changes in VILIP and NCS-1, two neuron-specific calcium-binding proteins. The Journal of biological chemistry 90 7806504
1999 Cellular and subcellular distribution of the calcium-binding protein NCS-1 in the central nervous system of the rat. Cell and tissue research 70 10022960
1995 Identification of neuronal calcium sensor (NCS-1) possibly involved in the regulation of receptor phosphorylation. Journal of receptor and signal transduction research 62 8903951
2009 Frequenin/NCS-1 and the Ca2+-channel alpha1-subunit co-regulate synaptic transmission and nerve-terminal growth. Journal of cell science 57 19861494
2010 Paclitaxel accelerates spontaneous calcium oscillations in cardiomyocytes by interacting with NCS-1 and the InsP3R. Journal of molecular and cellular cardiology 56 20801127
2018 NCS-1 is a regulator of calcium signaling in health and disease. Biochimica et biophysica acta. Molecular cell research 50 29746899
2013 GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis. The Journal of general physiology 50 24081984
2006 Analysis of the interacting partners of the neuronal calcium-binding proteins L-CaBP1, hippocalcin, NCS-1 and neurocalcin delta. Proteomics 50 16470652
2015 Origin, diversification and substrate specificity in the family of NCS1/FUR transporters. Molecular microbiology 47 25712422
2012 Multiple roles for frequenin/NCS-1 in synaptic function and development. Molecular neurobiology 40 22396213
2007 Specificity, promiscuity and localization of ARF protein interactions with NCS-1 and phosphatidylinositol-4 kinase-III beta. Traffic (Copenhagen, Denmark) 37 17555535
2017 Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome. Proceedings of the National Academy of Sciences of the United States of America 35 28119500
2006 Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence. The pharmacogenomics journal 34 16402081
1995 Distribution pattern of three neural calcium-binding proteins (NCS-1, VILIP and recoverin) in chicken, bovine and rat retina. The Histochemical journal 34 7591845
2012 NCS-1 associates with adenosine A(2A) receptors and modulates receptor function. Frontiers in molecular neuroscience 32 22529776
2008 Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients. Progress in neuro-psychopharmacology & biological psychiatry 32 19091302
2012 FREQ-Seq: a rapid, cost-effective, sequencing-based method to determine allele frequencies directly from mixed populations. PloS one 29 23118913
2014 NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice. Physiology & behavior 28 24631552
2014 The guanine-exchange factor Ric8a binds to the Ca²⁺ sensor NCS-1 to regulate synapse number and neurotransmitter release. Journal of cell science 28 25074811
2009 Proteomic and functional analysis of NCS-1 binding proteins reveals novel signaling pathways required for inner ear development in zebrafish. BMC neuroscience 28 19320994
2004 MGluRs regulate the expression of neuronal calcium sensor proteins NCS-1 and VILIP-1 and the immediate early gene arg3.1/arc in the hippocampus in vivo. Biochemical and biophysical research communications 26 15336574
2015 Self-directed exploration provides a Ncs1-dependent learning bonus. Scientific reports 25 26639399
2007 DARPP-32 and NCS-1 expression is not altered in brains of rats treated with typical or atypical antipsychotics. Neurochemical research 25 17763944
2017 Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival. Molecular cancer research : MCR 22 28275088
2003 Developmental expression of NCS-1 (frequenin), a regulator of Kv4 K+ channels, in mouse heart. Pediatric research 22 12612193
2002 NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway. The Journal of biological chemistry 22 12011096
2005 Expression of the neuronal calcium sensor protein NCS-1 in the developing mouse olfactory pathway. The Journal of comparative neurology 19 15611992
2019 Characterization of NCS1-InsP3R1 interaction and its functional significance. The Journal of biological chemistry 18 31659121
2016 Cryptic purine transporters in Aspergillus nidulans reveal the role of specific residues in the evolution of specificity in the NCS1 family. Molecular microbiology 16 27741561
2009 Discrete proteolysis of neuronal calcium sensor-1 (NCS-1) by mu-calpain disrupts calcium binding. Cell calcium 16 19732951
2008 NCS-1 differentially regulates growth cone and somata calcium channels in Lymnaea neurons. The European journal of neuroscience 16 18279316
2018 Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 30592625
2019 NCS-1 Deficiency Affects mRNA Levels of Genes Involved in Regulation of ATP Synthesis and Mitochondrial Stress in Highly Vulnerable Substantia nigra Dopaminergic Neurons. Frontiers in molecular neuroscience 14 31827421
2015 Membrane binding of Neuronal Calcium Sensor-1 (NCS1). Colloids and surfaces. B, Biointerfaces 14 26705828
2008 Methylphenidate alters NCS-1 expression in rat brain. Neurochemistry international 14 18514368
2010 Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1. Journal of negative results in biomedicine 13 20565907
2021 Neuronal calcium sensor 1 (NCS1) dependent modulation of neuronal morphology and development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 34499766
2019 NCS-1 Deficiency Is Associated With Obesity and Diabetes Type 2 in Mice. Frontiers in molecular neuroscience 10 31001084
2006 NCS-1 expression in rat brain after electroconvulsive stimulation. Neurochemical research 10 17160505
2019 NCS-1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin. Molecular oncology 9 31647602
2014 Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis. Synapse (New York, N.Y.) 9 24978930
2008 Molecular characterization of the Aspergillus fumigatus NCS-1 homologue, NcsA. Molecular genetics and genomics : MGG 9 18830711
2022 NCS1 overexpression restored mitochondrial activity and behavioral alterations in a zebrafish model of Wolfram syndrome. Molecular therapy. Methods & clinical development 8 36320410
2004 Disruption of the NCS-1/frequenin-related ncsA gene in Dictyostelium discoideum accelerates development. Development, growth & differentiation 8 15606490
2010 Downregulation of the cAMP/PKA pathway in PC12 cells overexpressing NCS-1. Cellular and molecular neurobiology 7 20838877
2003 Identification and subcellular localization of neuronal calcium sensor-1 (NCS-1) in human neutrophils and HL-60 cells. Inflammation 7 14760944
2024 NCS-1 protein regulates TRPA1 channel through the PI3K pathway in breast cancer and neuronal cells. Journal of physiology and biochemistry 6 38564162
2020 Calcium Binding Protein Ncs1 Is Calcineurin Regulated in Cryptococcus neoformans and Essential for Cell Division and Virulence. mSphere 6 32907953
2015 Heterologous complementation studies reveal the solute transport profiles of a two-member nucleobase cation symporter 1 (NCS1) family in Physcomitrella patens. Plant physiology and biochemistry : PPB 6 26773540
2001 Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage. Molecular and cellular endocrinology 6 11694341
2021 Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice. Scientific reports 5 33504822
2020 Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition. Scientific reports 5 32165725
2023 The neuronal calcium sensor NCS-1 regulates the phosphorylation state and activity of the Gα chaperone and GEF Ric-8A. eLife 3 38018500
2022 The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes. Frontiers in neuroscience 3 36466176
2023 Distinct mechanism of Tb3+ and Eu3+ binding to NCS1. Physical chemistry chemical physics : PCCP 2 36938969
2023 Generation of an NCS1 gene knockout human induced pluripotent stem cell line using CRISPR/Cas9. Stem cell research 2 37984032
2021 Foxp3 attenuates cerebral ischemia/reperfusion injury through microRNA-150-5p-modified NCS1. Experimental cell research 2 34822811
2016 Putative orotate transporter of Cryptococcus neoformans, Oat1, is a member of the NCS1/PRT transporter super family and its loss causes attenuation of virulence. Current genetics 2 28011993
2010 Inhibitory avoidance task does not change NCS-1 level in rat brain. Brain research bulletin 2 20493243
2024 Substrate identification of putative NCS1 and NCS2 nucleobase transporters in Pseudomonas aeruginosa. mBio 1 39475230
2026 Spinal overexpression of CAPN1 in CaMKII neurons mediates paclitaxel-induced neuropathic pain via NCS-1-TRPV4 signaling. Molecular pain 0 41482880
2026 An AI-based approach accelerates the discovery of protein-protein interaction modulators targeting NCS-1. European journal of medicinal chemistry 0 41785832
2025 The DLX1-NCS1-MYC axis drives oncogenesis and progression in lung adenocarcinoma. Biochimica et biophysica acta. Molecular basis of disease 0 40614386
2025 FDA Drug Repurposing Uncovers Modulators of Dopamine D2 Receptor Localization via Disruption of the NCS-1 Interaction. Journal of medicinal chemistry 0 41211723
2024 Interactions of Li+ ions with NCS1: A potential mechanism of Li+ neuroprotective action against psychotic disorders. Journal of inorganic biochemistry 0 39447483
2024 Stress survival and longevity of Caenorhabditis elegans lacking NCS-1. Toxicology research 0 39555232