Affinage

SLC8A1

Sodium/calcium exchanger 1 · UniProt P32418

Length
973 aa
Mass
108.5 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC8A1 (NCX1) is a bidirectional plasma-membrane Na+/Ca2+ antiporter that couples transmembrane Na+ and Ca2+ gradients to govern Ca2+ homeostasis in cardiac, neuronal, glial, skeletal-muscle, and epithelial cells (PMID:11916852, PMID:23761399). The transporter is built on a 10-transmembrane fold with two alpha-repeat re-entrant loops forming the ion-interaction site, where specific residues set divalent/monovalent selectivity, and a large intracellular regulatory loop carrying tandem Ca2+-binding domains CBD1 (high affinity) and CBD2 (low affinity, fast off-rate) that allosterically tune activity (PMID:23376057, PMID:10438478, PMID:19141619). Its activity is shaped by two intrinsic regulatory processes — Na+-dependent (I1) inactivation mediated by the XIP region and Ca2+-dependent (I2) inactivation — and a cryo-EM structure shows the XIP trapped in a groove between the transport domain and CBD2 to promote inactivation, with the inhibitor SEA0400 acting allosterically through helix TM2ab (PMID:38177313, PMID:14978259). Tissue-specific alternative splicing of mutually exclusive exons A and B in the intracellular loop produces isoforms with distinct ionic regulation, with residues D610/K617 in exon A enabling Ca2+-dependent relief of Na+ inactivation (PMID:9142850, PMID:10539974, PMID:12118014). NCX1 is embedded in macromolecular signaling complexes — anchored to PKA/PKC/PP1/PP2A via mAKAP and bound by calmodulin — and is regulated by PKA/PKC phosphorylation, by S-nitrosylation at Cys730, and by palmitoylation at Cys739 (written by zDHHC5, erased by APT1) that is dispensable for transport but required for Na+-dependent inactivation (PMID:12754202, PMID:26421717, PMID:21159997, PMID:31935590, PMID:33873072). Functionally, Na+-dependent inactivation is essential for normal cardiac excitability and contractility (PMID:38714663), and NCX1 drives sinoatrial pacemaking (PMID:23761399), while channel partners such as TRPC3/TRPC6/TRPC1, NHE1, and SUR1-TRPM4 supply local Na+ loads that switch NCX1 into reverse (Ca2+-entry) mode to support cardiac arrhythmogenesis, dystrophic muscle Ca2+ overload, astrocytic edema, and tumor cell migration (PMID:17129578, PMID:18996841, PMID:24662047, PMID:37279286, PMID:35882979). Its transcription is dynamically controlled by activators (HIF-1/Sp1/p300, GATA-4, SRF, MTF-1) and repressors (REST/CoREST, Sp3/HDAC1/HDAC2, HDAC5-scaffolded complexes), and by miRNAs miR-1 and miR-103-1, coupling NCX1 levels to ischemic stress and cardiac remodeling (PMID:21293012, PMID:10409212, PMID:23069678, PMID:25972164, PMID:33931586, PMID:23436819, PMID:24954474).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Establishing that NCX1 is diversified by tissue-specific alternative splicing explained how a single gene generates regionally distinct Ca2+-handling behavior.

    Evidence RT-PCR across tissue panels and developmental stages mapping mutually exclusive exons A/B and exons C-F

    PMID:9142850

    Open questions at the time
    • Splicing pattern did not establish the functional consequence of each isoform
    • No structural localization of the variable exons within the protein
  2. 1999 High

    Demonstrating that the A/B exons confer opposite ionic-regulatory phenotypes converted a splicing observation into a functional regulatory mechanism.

    Evidence Giant excised patches from Xenopus oocytes comparing exon-A (brain) and exon-B (kidney) isoforms

    PMID:10539974

    Open questions at the time
    • Did not identify the precise residues responsible
    • Regulation tested in oocytes, not native cells
  3. 2002 High

    Pinpointing D610/K617 in exon A identified the molecular determinant of Ca2+-dependent relief of Na+ inactivation, linking splice choice to specific gating residues.

    Evidence Site-directed mutagenesis and chimeric exchangers with giant-patch electrophysiology

    PMID:12118014

    Open questions at the time
    • Mechanism by which these residues couple Ca2+ binding to inactivation relief not resolved structurally at the time
  4. 1999 High

    Mapping ion-selectivity residues in the alpha-repeats defined where ions interact with the transporter.

    Evidence NCX1/NCX3 chimeras and mutagenesis (N125/T127, V820, Q826) with 45Ca2+ uptake

    PMID:10438478

    Open questions at the time
    • Did not resolve the full transport pathway
    • Selectivity inferred from drug/ion sensitivity rather than direct ion binding
  5. 2002 High

    Precise biophysical measurement of coupling ratios established NCX1 as an electrogenic exchanger moving net charge per cycle.

    Evidence Whole-cell voltage clamp and reversal-potential measurement of recombinant NCX1.1 in HEK-293

    PMID:11916852

    Open questions at the time
    • Exact stoichiometry numbers differed from canonical 3:1 model
    • Did not address conformational basis of coupling
  6. 2000 High

    Identifying PKA- and Ca2+-regulatory determinants and isoform-specific PKA sensitivity showed NCX1 activity is set by phosphorylation and intracellular regulatory sites.

    Evidence Two-electrode voltage clamp, cardiomyocyte flux assays, and CCL39 mutant analysis of D447/D498 and XIP

    PMID:10913006 PMID:11118492

    Open questions at the time
    • PKC stimulation shown not to require direct exchanger phosphorylation, leaving the adaptor mechanism open [#1]
  7. 2003 High

    Defining the mAKAP-anchored PKA/PKC/PP1/PP2A complex established NCX1 as a node within a localized cardiac signaling platform.

    Evidence Reciprocal co-IP, in vitro PKA phosphorylation, and dual immunocytochemistry in cardiac myocytes

    PMID:12754202

    Open questions at the time
    • Functional consequence of each kinase/phosphatase on transport in vivo not fully dissected
    • Leucine zipper interaction sites inferred, not proven structurally
  8. 2004 High

    Linking SEA0400 block to the Na+-dependent (I1) inactivation state revealed that pharmacology exploits an intrinsic gating mechanism.

    Evidence Chimeric/mutant NCX1.1 panels in giant patches and whole-cell currents with SEA0400

    PMID:14660663 PMID:14978259

    Open questions at the time
    • Atomic binding site of SEA0400 not defined until later structural work
  9. 2009 High

    Quantifying CBD1/CBD2 Ca2+ affinities and kinetics established the biochemical basis for allosteric Ca2+ sensing.

    Evidence Stopped-flow kinetics and equilibrium binding on purified CBD1, CBD2, and CBD12 proteins

    PMID:19141619

    Open questions at the time
    • How CBD occupancy is transmitted to the transport domain not resolved
    • Used isolated domains, not full-length transporter
  10. 2013 High

    Cysteine crosslinking corrected the topology to 10 transmembrane segments, aligning NCX1 with its prokaryotic homolog and grounding later structural interpretation.

    Evidence Cysteine crosslinking and accessibility biochemistry

    PMID:23376057

    Open questions at the time
    • Did not provide atomic-resolution structure
  11. 2010 High

    Identifying isoform-specific NO-sensitive residues (Cys730 in NCX1) showed nitrosylation as a direct, cGMP-independent post-translational regulator.

    Evidence Fura-2 microfluorometry, patch-clamp, and chimeric/mutant exchangers in BHK cells

    PMID:21159997

    Open questions at the time
    • Physiological contexts driving Cys730 nitrosylation not defined
  12. 2015 High

    Defining a Ca2+-dependent calmodulin-binding segment showed CaM directly regulates exchange activity and membrane localization.

    Evidence CaM pulldowns of the intracellular loop and Ca2+ influx assays with CaMS deletions/point mutants in HEK293T

    PMID:26421717

    Open questions at the time
    • Differential effects across splice variants not mechanistically explained
  13. 2020 High

    Identifying Cys739 palmitoylation and its adjacent amphipathic helix uncovered a lipid modification selectively required for Na+-dependent inactivation rather than transport.

    Evidence Site-directed mutagenesis, palmitoylation assays, and NCX1 activity assays

    PMID:31935590

    Open questions at the time
    • Enzymes catalyzing the modification not yet identified at this stage
  14. 2021 High

    Assigning zDHHC-PATs as writers and APT1 as the Golgi eraser established a dynamic palmitoylation cycle controlling NCX1 organization.

    Evidence zDHHC-PAT palmitoylation screen, thioesterase knockdown, and subcellular localization

    PMID:33873072

    Open questions at the time
    • Physiological signals controlling the cycle addressed only later
  15. 2022 High

    Linking insulin to zDHHC5-dependent palmitoylation connected metabolic signaling to NCX1 inactivation tuning.

    Evidence Palmitoylation and activity assays with zDHHC5 knockout/inhibition and structural proximity assays

    PMID:35231700

    Open questions at the time
    • In vivo cardiac/metabolic relevance of insulin-driven palmitoylation not established
  16. 2023 High

    The cryo-EM structure of NCX1.3 visualized how the XIP and SEA0400 promote inactivation, unifying decades of mutational gating data into a structural mechanism.

    Evidence Cryo-EM of the inward-facing inhibitor-bound human NCX1.3

    PMID:38177313

    Open questions at the time
    • Outward-facing and transport-cycle intermediates not captured in this structure
    • Splice-isoform structural differences not resolved
  17. 2013 High

    Sinoatrial-specific knockout established NCX1 as essential for cardiac pacemaking and synchronized Ca2+ transients, complementing the zebrafish null phenotype.

    Evidence Inducible SA-node-specific Cre NCX1 knockout mice with Ca2+ imaging and patch-clamp; zebrafish tremblor mutant with mosaic rescue

    PMID:16314583 PMID:23761399

    Open questions at the time
    • Quantitative contribution of NCX1 to the pacemaker current relative to other mechanisms remained debated
  18. 2024 High

    A CRISPR knock-in removing only Na+-dependent inactivation (K229Q) proved this single regulatory mechanism is required for normal cardiac excitability and contractility in vivo.

    Evidence K229Q knock-in mice with echocardiography, patch-clamp, and Ca2+ transient imaging

    PMID:38714663

    Open questions at the time
    • Whether human NCX1 variants disrupting inactivation cause analogous disease not established
  19. 2022 High

    Defining TRPC/NHE1/SUR1-TRPM4 partners that locally load Na+ explained how NCX1 is switched into reverse (Ca2+-entry) mode in pathology across heart, muscle, brain, and cancer.

    Evidence Co-IP/FRET, dominant-negative and siRNA functional rescue, transgenic and astrocyte/muscle-specific KO models linking Na+ partners to NCX1 reverse-mode Ca2+ entry

    PMID:17129578 PMID:18996841 PMID:24662047 PMID:25631581 PMID:29500176 PMID:35882979 PMID:37279286

    Open questions at the time
    • Stoichiometry and structural basis of these microdomain complexes unresolved
    • Several cancer/cell-type complexes rest on single-lab co-IP evidence
  20. 2021 High

    Mapping transcriptional and post-transcriptional control showed NCX1 levels are dynamically set by competing activator/repressor complexes and miRNAs, particularly under ischemic and remodeling stress.

    Evidence ChIP/EMSA, promoter-reporter, site-directed mutagenesis, in vivo siRNA, knockout mice, and 3'UTR luciferase assays for HIF-1/Sp1/p300, GATA-4, SRF/miR-1, REST/CoREST, Sp3/HDAC, HDAC5, MTF-1, and miR-103-1

    PMID:10409212 PMID:19164785 PMID:21293012 PMID:23069678 PMID:23436819 PMID:24954474 PMID:25972164 PMID:26704971 PMID:33931586

    Open questions at the time
    • How these factors are integrated at the endogenous locus in a given cell state not fully reconciled
    • Tissue specificity of each regulator only partly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NCX1's intrinsic gating, lipid/post-translational modifications, and partner-supplied local ion gradients are integrated to set forward- versus reverse-mode operation in specific physiological and disease microdomains remains unresolved.
  • No structure of the full-length transporter in multiple cycle states with regulatory partners bound
  • Causal human Mendelian disease link not established in the corpus
  • In vivo significance of metabolic (insulin/palmitoylation) and nitrosylation regulation largely untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 2 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-382551 Transport of small molecules 2 R-HSA-397014 Muscle contraction 2
Partners
ANO6CALMODULINEAAC1MAKAPNHE1TRPC1TRPC3TRPC6

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NCX1 undergoes tissue-specific alternative splicing of six exons (A, B, C, D, E, F) in a large intracellular loop. Exons A and B are mutually exclusive; exon A isoforms are preferentially expressed in heart, brain, and skeletal muscle, while exon B isoforms are found in all tissues except heart. Developmental regulation of NCX1 splicing isoforms was detected in skeletal muscle. RT-PCR across multiple tissues and developmental stages The American journal of physiology High 9142850
1998 PKC-dependent stimulation of NCX1 and NCX3 (but not NCX2) requires the central cytoplasmic loop but does not require direct phosphorylation of the exchanger. Three PKC phosphorylation sites (Ser-249, Ser-250, Ser-357) were identified in NCX1, with Ser-250 predominantly phosphorylated; however, mutation of these sites did not abolish PMA response. Site-directed mutagenesis, [32P]orthophosphate labeling, immunoprecipitation, 45Ca2+ uptake assay Biochemistry High 9860837
1998 NCX1, NCX2, and NCX3 show similar apparent affinities for transported ions Na+ and Ca2+ at both membrane surfaces. ATP depletion inhibited NCX1 and NCX2 but not NCX3. NCX1 and NCX3 were modestly stimulated by PKA and PKC activators. All three exchangers were regulated by intracellular Ca2+. NCX1 exchange currents were stimulated by ATP in excised patches. 45Ca2+ uptake assay (intact cells and vesicles), giant patch electrophysiology, stable expression in BHK cells The American journal of physiology High 9486131
1999 The mutually exclusive A and B exons of NCX1 determine distinct ionic regulatory properties. Exon B (NCX1.3/kidney) confers more pronounced Na+-dependent inactivation and inhibition at high [Ca2+]i, while exon A (NCX1.4/brain) allows Ca2+i to relieve Na+-dependent inactivation. Giant excised patches from Xenopus oocytes expressing cloned exchangers, multiple ionic regulatory protocols The Journal of general physiology High 10539974
1999 The alpha-1 and alpha-2 repeat regions of NCX1 determine differential sensitivity to external Ni2+ and Li+. Specific residues N125/T127 (alpha-1) and V820 (alpha-2) in NCX1 were identified as critical determinants of Ni2+ sensitivity; V820/Q826 in alpha-2 determines Li+ sensitivity. These putative loop regions may form an ion interaction domain. NCX1/NCX3 chimeras, site-directed mutagenesis, 45Ca2+ uptake in CCL39 cells The Journal of biological chemistry High 10438478
1999 Cardiac expression of NCX1 is dependent on GATA-4. A GATA-4 site at -75 bp is required for >90% of minimum promoter activity; mutation abolishes GATA-4 binding by gel shift assay. A second GATA site at -145 contributes ~30% of full-length promoter activity. Gel shift and supershift assay, site-directed mutagenesis of GATA sites, promoter-reporter transfection in primary neonatal cardiomyocytes The American journal of physiology High 10409212
2000 Cardiac (NCX1.1) and renal (NCX1.3) isoforms differ in activation by PKA and sensitivity to depolarizing voltages. The cardiac isoform is more sensitive to PKA activation than renal isoform, and cardiac NCX1.1 is phosphorylated to a greater extent. PKA phosphorylation increases NCX1 cardiac isoform activity, confirmed in adult rat ventricular cardiomyocytes. Two-electrode voltage clamp in Xenopus oocytes, Na+-dependent Ca2+ flux in adult cardiomyocytes The Journal of physiology High 11118492
2000 The Ca2+-regulatory site (mutant D447V/D498I) of NCX1 is required for efficient Ca2+ extrusion, especially during small Ca2+ rises. The XIP region (Na+-inactivation) mutant (XIP-4YW) accelerated cell death under Na+ load and was not activated by PKC. The Ca2+-regulatory and XIP region mutants were resistant to inhibition by ATP depletion. Functional Ca2+ handling assays and cell viability in CCL39 cells expressing site-directed mutants American journal of physiology. Cell physiology High 10913006
2002 NCX1.1 stoichiometry measured in HEK-293 cells expressing recombinant exchanger is 4 Na+ to 1 Ca2+ to 2 net charges per transport cycle, consistent with 3 Na+:1 Ca2+ with 1 net charge in original models but here more precisely measured as coupling ratios of 1.9–2.3 Na+ per net charge and 0.45 Ca2+ per net charge. Whole-cell voltage clamp, reversal potential measurement under varied ionic conditions Biophysical journal High 11916852
2002 Aspartic acid at position 610 and lysine at position 617 (in NCX1.4 numbering) within exon A are critical molecular determinants for Ca2+-dependent relief of Na+-dependent inactivation. Replacing D610 with Arg (corresponding to exon B) abolished Ca2+ regulation of I1 inactivation in exon A background; the double mutant in exon B background restored NCX1.4 regulatory phenotype. Site-directed mutagenesis, chimeric exchangers, giant excised patches from Xenopus oocytes The Journal of biological chemistry High 12118014
2002 NCX1 is found at both pre- and postsynaptic sites and associated with endoplasmic reticulum membranes in brain neurons, as demonstrated by immunoelectron and confocal microscopy. Immunoelectron microscopy, confocal microscopy with isoform-specific probes Annals of the New York Academy of Sciences Medium 12502586
2003 NCX1 forms a macromolecular complex in cardiac myocytes that includes PKA catalytic and RI regulatory subunits (not RII), PKC, PP1, and PP2A, anchored by mAKAP. NCX1 is dynamically phosphorylated by PKA in vitro. Leucine/isoleucine zipper motifs were identified as possible interaction sites. Co-immunoprecipitation, in vitro PKA phosphorylation, dual immunocytochemistry with colocalization The Journal of biological chemistry High 12754202
2003 SEA0400 inhibits NCX1 preferentially over NCX2, NCX3, and NCKX2. The first intracellular loop and fifth transmembrane segment determine differential drug sensitivity. Phe-213 mutation markedly reduces SEA0400 sensitivity. Gly-833 (alpha-2 repeat) mutation also greatly reduces SEA0400 sensitivity. Exchangers with abolished Na+-dependent inactivation show reduced SEA0400 sensitivity, while those with accelerated I1 inactivation show hypersensitivity, indicating I1 inactivation is part of the inhibitory mechanism. NCX1/NCX3 chimeric analysis, site-directed mutagenesis, 45Ca2+ uptake, whole-cell exchange currents The Journal of biological chemistry High 14660663
2004 SEA0400 block of NCX1.1 requires Na+-dependent (I1) inactivation. Mutants lacking I1 inactivation show greatly reduced SEA0400 effect; mutants with accelerated I1 show enhanced or unchanged block; I2 (Ca2+-dependent) inactivation suppression does not affect SEA0400 block. Mutant NCX1.1 exchangers with altered ionic regulation in giant patches, pharmacological SEA0400 application Molecular pharmacology High 14978259
2005 Loss-of-function of the cardiac-specific zebrafish NCX1 homolog (NCX1h) causes cardiac fibrillation and loss of synchronized Ca2+ transients. Forced expression of NCX1h or other Ca2+-handling molecules restored synchronized heartbeats in a dose-dependent manner. Mosaic analysis showed clustered wild-type cardiomyocytes can contract in unison even in NCX1h-null hearts. Zebrafish tremblor mutant characterization, molecular cloning, Ca2+ imaging, mosaic rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 16314583
2006 TRPC3 physically associates with NCX1 in rat cardiac myocytes. TRPC3-mediated Na+ loading drives NCX1-mediated Ca2+ entry (PLC-dependent). PLC stimulation recruits both TRPC3 and NCX1 to the plasma membrane. Expression of dominant-negative TRPC3 suppresses NCX-mediated Ca2+ signaling. Reciprocal co-immunoprecipitation, GST-pulldown, surface biotinylation, immunocytochemistry colocalization, Ca2+ fluorimetry with dominant-negative knockdown Cardiovascular research High 17129578
2006 NCX1 localizes predominantly to neuropilar puncta in rat neocortex and hippocampus, with expression in dendritic spines contacted by asymmetric axon terminals, in astrocytes, and in perivascular astrocytic endfeet and endothelial cells. NCX1 shows perisynaptic postsynaptic localization. Immunocytochemistry with isoform-specific antibodies, confocal microscopy Cell calcium Medium 16914199
2007 NCX1, NCX2, and NCX3 proteins are expressed in mitochondria of neurons and astrocytes in rat neocortex and hippocampus. Neuronal mitochondria expressing NCX1-3 are particularly abundant in dendrites near postsynaptic sites. Western blotting on mitochondrial fractions, immunoelectron microscopy in situ Pharmacological research Medium 18024055
2008 Upon integrin alphaIIbbeta3 activation by ligand, NHE1 and NCX1 are transported to the plasma membrane and physically coupled to integrin alphaIIbbeta3 in a lipid raft-dependent complex. NHE1 generates local Na+ increase that drives NCX1 in reverse mode to produce Ca2+ influx, triggering calcium oscillation. Co-immunoprecipitation, fluorescence resonance energy transfer (FRET/FLIM), surface membrane transport assays The Journal of biological chemistry High 18996841
2009 NCX1 upregulation in cortical neurons under anoxia is mediated by NF-κB (specifically p65 subunit) at the transcriptional level. NF-κB translocation inhibition (by siRNA against p65 or SN-50) prevented OGD-induced NCX1 upregulation. NCX1 upregulation promotes ER Ca2+ refilling; NCX1 silencing prevented ER Ca2+ accumulation and triggered caspase-12 activation. siRNA knockdown of p65, RT-PCR, Western blot, patch-clamp, Fura-2 single-cell microfluorometry in primary cortical neurons Stroke High 19164785
2009 Kinetic characterization of NCX1 calcium-binding domains CBD1 and CBD2: CBD1 has higher Ca2+ affinity (Kd ~0.3 µM) than CBD2 (Kd ~5 µM); Ca2+ dissociation from CBD2 is ~25× faster than from CBD1. CBD12 tandem binds ~6 Ca2+ ions; Mg2+ has little effect on Ca2+ off-rates. Na+ does not compete with Ca2+ for any CBD site. Stopped-flow kinetics, equilibrium Ca2+ binding assays with purified CBD1, CBD2, CBD12 proteins The Journal of biological chemistry High 19141619
2009 NCX1 expression and reverse-mode activity increase in microglia invading the ischemic infarct core after permanent MCAO. In NCX1-silenced BV2 cells, hypoxia-induced [Ca2+]i increase was completely prevented. Western blotting, patch-clamp electrophysiology, Fura-2 microfluorometry, immunohistochemistry, ex vivo primary microglia isolation Stroke High 19745171
2010 NO stimulates NCX1 activity in a cGMP-independent manner via nitrosylation of Cys730 in the f-loop (residues 723–734). NO stimulates NCX2 via a cGMP-dependent mechanism at Ser713. NO inhibits NCX3 in a cGMP-independent manner at Cys156 in the alpha-1 region. NCX3 chimeras carrying NCX1 or NCX2 NO-sensitive segments become NO-activated. Single-cell Fura-2 microfluorometry, patch-clamp, deletion and site-directed mutagenesis, chimeric exchangers in BHK transfectants Molecular pharmacology High 21159997
2011 NCX1 gene is a direct transcriptional target of HIF-1α. HIF-1 binds two hypoxia-responsive elements (HREs) on the brain NCX1 promoter. HIF-1α silencing prevents NCX1 upregulation and neuroprotection during ischemic preconditioning. NCX1 silencing partially reverts preconditioning-induced neuroprotection in rats. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation, siRNA knockdown in vivo and in vitro Stroke High 21293012
2012 NCX1 physically interacts with EAAC1 glutamate transporter in neuronal and glial mitochondria. NCX1 activity is required for EAAC1-mediated glutamate-stimulated ATP production in brain mitochondria. NCX1 antisense oligonucleotide knockdown prevented glutamate-stimulated ATP synthesis. Colocalization by confocal and immunoelectron microscopy, co-immunoprecipitation, pharmacological blockade, antisense knockdown, luciferase-luciferin ATP assay PloS one High 22479505
2012 REST is a transcriptional repressor of NCX1 that recruits CoREST (not mSin3A) and causes H4 deacetylation at the ncx1 brain promoter. REST binds the ncx1 promoter in sequence-specific manner. REST overexpression reduces NCX1 protein and activity; REST silencing increases NCX1 expression and reduces infarct volume. REST silencing with NCX1 double silencing abolished neuroprotection. ChIP, siRNA, site-directed mutagenesis of REST binding site, promoter-reporter assay, in vivo rat tMCAO model Neurobiology of disease High 23069678
2013 NCX1 has 10 transmembrane segments (TMSs) as in the prokaryotic homologue, not 9 as previously modeled. C-terminal TMS8 exists; cysteine crosslinking between N-terminal and C-terminal cysteines supports the 10-TMS model. Cysteine crosslinking/accessibility studies, biochemical analysis Journal of molecular and cellular cardiology High 23376057
2013 SRF regulates NCX1 transcription; miR-1 (regulated by SRF) post-transcriptionally represses NCX1 and AnxA5 mRNA translation. In SRF knockout hearts, NCX1 mRNA decreases but protein increases due to reduced miR-1. Site-directed mutagenesis confirmed NCX1 and AnxA5 mRNAs as direct miR-1 targets. AnxA5 overexpression slows Ca2+ extrusion via NCX1. SRF knockout mice, miR-1 manipulation in vivo and in vitro, site-directed mutagenesis of miR-1 binding sites, caffeine Ca2+ transient assay Cardiovascular research High 23436819
2013 Sinoatrial node-specific knockout of NCX1 causes progressive bradycardia, severe arrhythmias, and irregular spontaneous Ca2+ discharges in pacemaker cells. NCX1-null pacemaker cells show no NCX1 activity after caffeine-induced Ca2+ release, reduced frequency and amplitude of Ca2+ transients during field stimulation. Inducible sinoatrial-specific Cre NCX1 knockout mice, Ca2+ imaging, patch-clamp, RT-PCR, immunolabeling Cardiovascular research High 23761399
2014 NCX1 upregulation via the Akt/CREB1 transcriptional pathway and NCX3 upregulation via proteasome inhibition (post-transcriptional) both contribute to the prosurvival effect of PI3K/Akt. Silencing of NCX1 or NCX3 reduced Akt1-mediated prosurvival activity during chemical hypoxia. Doxycycline-inducible constitutively active Akt1 in PC-12 cells, siRNA, proteasome inhibitor MG-132, NCX activity assay Molecular pharmacology Medium 18079274
2014 miR-103-1 directly represses NCX1 expression in brain neurons via targeting the NCX1 3'UTR (confirmed by luciferase assay). Anti-miR-103-1 prevented NCX1 downregulation after ischemia and reduced brain infarct volume and neurological deficits in rats. Luciferase reporter assay, antimiRNA treatment in rat transient ischemia model, Western blot Molecular therapy High 24954474
2014 NCX1 entry operates in reverse mode in dystrophic skeletal muscle, contributing to Ca2+ overload and pathology. Skeletal muscle-specific NCX1 transgene induced dystrophy-like disease; muscle-specific Slc8a1 deletion diminished hind-limb pathology in δ-sarcoglycan null mice. Elevated baseline Na+ in dystrophic fibers predicts reverse-mode NCX1 operation. Skeletal muscle-specific transgenic overexpression and knockout mice, multiple dystrophy mouse model crosses, Na+ and Ca2+ measurements, ranolazine treatment Molecular and cellular biology High 24662047
2014 NCX1 co-immunoprecipitates with GAP-43 in neuronal cells and its silencing prevents NGF-induced Akt phosphorylation, GAP-43 expression, and neurite outgrowth. NCX1.4 overexpression increases ER Ca2+ content and Na+ levels via tetrodotoxin-sensitive Na+ currents, promoting Ca2+-dependent Akt phosphorylation and differentiation. Co-immunoprecipitation, siRNA, overexpression of NCX1.4 splice variant, Ca2+ and Na+ imaging, neurite length measurement in PC12 and cortical neurons The Journal of biological chemistry High 25416782
2015 The Sp3/REST/HDAC1/HDAC2 complex represses ncx1 brain promoter via H4 deacetylation during ischemia (tMCAO). The Sp1/HIF-1/p300 complex activates ncx1 brain promoter via hyperacetylation during ischemic preconditioning. Both Sp1 and Sp3 bind ncx1 promoter Sp1 sites C-E in a sequence-specific manner. Class I HDAC inhibitor MS-275 neuroprotection was counteracted by NCX1 silencing; p300 inhibitor toxicity was prevented by NCX1 overexpression. ChIP, EMSA, siRNA, site-directed mutagenesis of promoter elements, in vivo rat tMCAO, in vitro OGD/RX model The Journal of neuroscience High 25972164
2015 Calmodulin binds the intracellular loop of NCX1 in a Ca2+-dependent manner at a specific CaM-binding segment (CaMS). Deletion of the CaMS from NCX1.1 or NCX1.3 reduces exchange activity and membrane localization. Point mutations at conserved CaMS residues have differential effects on activity in NCX1.1 vs NCX1.3 splice variants. CaM pulldown of intracellular loop subclones, co-expression with CaM or Ca2+-binding deficient CaM1234, Ca2+ influx assay in HEK293T cells, deletion and point mutagenesis PloS one High 26421717
2015 NCX1 and calretinin co-immunoprecipitate from human SH-SY5Y cells. Calretinin silencing prevents preconditioning-induced NCX1 upregulation and activity as well as Akt activation, indicating calretinin is required for NCX1-mediated neuroprotection in the striatum. Co-immunoprecipitation, confocal microscopy, in vitro and in vivo calretinin siRNA, Fura-2 Ca2+ imaging Molecular neurobiology Medium 25633096
2015 Anoctamin-6 (Ano6) interacts with NCX1 (identified by two-hybrid split-ubiquitin screen). NCX1 requires Ano6 for efficient Ca2+ extrusion from osteoblasts; Ano6-/- osteoblasts lack Ca2+-activated anion currents and show impaired NCX1-mediated Ca2+ efflux for bone mineralization. Two-hybrid split-ubiquitin screen, osteoblasts from Ano6-/- mice, Ca2+ efflux assays, current recordings The Journal of biological chemistry High 25589784
2015 HDAC5 (class IIa) serves as a scaffold to recruit HDAC1/2/Sin3a co-repressor complexes and Nkx2.5/YY1 transcription factors to the Ncx1 promoter. HDAC5 KO prevents pressure overload-induced Ncx1 upregulation. HDAC5 is required for HDAC1/Sin3a co-repressor complex recruitment to the Ncx1 promoter. HDAC5-/- mice, transverse aortic constriction, ChIP, pharmacological class IIa HDAC inhibition Nucleic acids research High 26704971
2015 TRPC3 colocalization with NCX1 in cardiac myocytes supports a microdomain interaction that is disrupted upon TRPC3 activation. TRPC3 overexpression increases NCX1 currents following TRPC3 activation. Pro-arrhythmic effects outlast TRPC3 current activation and are suppressed by NCX inhibitor, demonstrating TRPC3-NCX1 coupling in arrhythmogenesis. TRPC3 transgenic mice, TRPC3-specific agonist GSK1702934A, NCX current measurement, immunocytochemistry colocalization, Langendorff hearts Cardiovascular research High 25631581
2018 TGFβ induces formation of a TRPC6/NCX1 molecular complex in hepatocellular carcinoma cells. TGFβ stimulates intracellular Ca2+ increase through both NCX1 and TRPC6. Positive feedback exists between TRPC6/NCX1 signaling and Smad signaling. This complex mediates TGFβ-induced migration, invasion, and metastasis. Co-immunoprecipitation, Ca2+ imaging, siRNA knockdown, invasion and migration assays, nude mouse xenograft Cancer research Medium 29500176
2020 NCX1 is palmitoylated at a single cysteine (Cys739) in its large regulatory intracellular loop. An amphipathic α-helix (residues 740–756) adjacent to the palmitoylation site is required for NCX1 palmitoylation. Palmitoylation does not regulate normal forward or reverse ion transport but is required for Na+-dependent inactivation and inactivation by PIP2 depletion. Mutagenesis of palmitoylation site, palmitoylation assays, functional NCX1 activity assays Cell calcium High 31935590
2021 NCX1 palmitoylation is catalyzed by multiple zDHHC-PATs; the NCX1 amphipathic α-helix directly interacts with zDHHC-PATs. The thioesterase APT1 (not APT2) catalyzes NCX1 depalmitoylation in the Golgi, governing NCX1 subcellular organization. NCX1 can be palmitoylated in both Golgi and ER. zDHHC-PAT palmitoylation screen, thioesterase knockdown, subcellular localization studies, protein interaction assays Cell calcium High 33873072
2021 MTF-1 (metal transcription factor-1) translocates to the nucleus and directly binds the metal responsive element (MRE) at -23/-17 bp of the Ncx1 brain promoter, activating NCX1 transcription during remote limb ischemic postconditioning (RLIP). MTF-1 silencing prevented RLIP-induced NCX1 upregulation and neuroprotection. ChIP, promoter-reporter assay, siRNA of MTF-1 in vivo, rat tMCAO + femoral artery occlusion model, infarct volume measurement Cell death & disease High 33931586
2022 Insulin triggers palmitoylation of NCX1 via a zDHHC5-dependent mechanism, inducing structural rearrangements within NCX1 dimers. Insulin activates fatty acid and fatty acyl CoA synthesis, promoting palmitoylation of the zDHHC5 active site, leading to enhanced NCX1 palmitoylation that tunes NCX1 inactivation. Palmitoylation assays, zDHHC5 knockout/inhibition, NCX1 activity assays, structural proximity assays, multiple cell types Cell calcium High 35231700
2022 TRPC1 and NCX1 co-localize and co-immunoprecipitate in gastric cancer cells. TRPC1 drives NCX1 to operate in Ca2+ entry mode, raising cytosolic Ca2+, which promotes proliferation, migration, and invasion through AKT/β-catenin signaling. Co-immunoprecipitation, Ca2+ imaging, siRNA knockdown, cell proliferation/invasion assays, xenograft mouse model Oncogene Medium 35882979
2023 Cryo-EM structure of human NCX1.3 with SEA0400 inhibitor reveals an inward-facing conformation. The exchanger-inhibitory peptide (XIP) is trapped in a groove between TMD and CBD2, clashing with gating helices TM1/6 in outward-facing state, thus promoting inactivation. SEA0400 binds and stiffens helix TM2ab, allosterically attenuating Ca2+-uptake activity. Cryo-EM structure determination, inhibitor-bound complex, structural analysis of XIP and SEA0400 binding sites The EMBO journal High 38177313
2023 In perivascular astrocyte endfeet, cerebral ischemia increases SUR1-TRPM4 and NCX1. Na+ influx through SUR1-TRPM4 induces NCX1 to operate in reverse mode (Ca2+ influx), raising intra-endfoot Ca2+, which triggers calmodulin-dependent AQP4 translocation to the plasma membrane and water influx causing cerebral edema. Pharmacological inhibition or astrocyte-specific deletion of NCX1 reduced brain swelling. Mouse ischemic stroke model, astrocyte-specific NCX1 deletion, pharmacological inhibition, Ca2+ imaging, brain edema measurement Science signaling High 37279286
2024 Na+-dependent inactivation of NCX1 is essential for normal cardiac function. CRISPR/Cas9 knock-in of K229Q mutation removes Na+-dependent inactivation while preserving transport properties. K229Q mice show reduced left ventricular ejection fraction, prolonged QT interval, enhanced NCX1 activity, action potential prolongation, aberrant action potentials, faster Ca2+ transient decline, and depressed cell shortening. CRISPR/Cas9 knock-in mouse model, echocardiography, patch-clamp electrophysiology, Ca2+ transient imaging, NCX1 activity assay Nature communications High 38714663

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Tissue specificity and alternative splicing of the Na+/Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in rat. The American journal of physiology 308 9142850
2018 A circular transcript of ncx1 gene mediates ischemic myocardial injury by targeting miR-133a-3p. Theranostics 212 30613267
1998 Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3). The American journal of physiology 175 9486131
2004 Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia. Stroke 134 15472108
2006 Cellular and subcellular localization of Na+-Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat. Cell calcium 118 16914199
2003 Sodium/calcium exchanger (NCX1) macromolecular complex. The Journal of biological chemistry 112 12754202
2003 Molecular determinants of Na+/Ca2+ exchange (NCX1) inhibition by SEA0400. The Journal of biological chemistry 109 14660663
1998 Protein kinase C-dependent regulation of Na+/Ca2+ exchanger isoforms NCX1 and NCX3 does not require their direct phosphorylation. Biochemistry 91 9860837
2015 Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by Epigenetic Mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 85 25972164
2007 BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential. Cell calcium 82 17343909
1999 Ionic regulatory properties of brain and kidney splice variants of the NCX1 Na(+)-Ca(2+) exchanger. The Journal of general physiology 82 10539974
2006 Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex. Cardiovascular research 77 17129578
2015 TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1. Cardiovascular research 74 25631581
2009 NCX1 expression and functional activity increase in microglia invading the infarct core. Stroke 73 19745171
2005 Mutation in sodium-calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish. Proceedings of the National Academy of Sciences of the United States of America 71 16314583
2002 Brain distribution of the Na+/Ca2+ exchanger-encoding genes NCX1, NCX2, and NCX3 and their related proteins in the central nervous system. Annals of the New York Academy of Sciences 70 12502586
2002 Stoichiometry of the Cardiac Na+/Ca2+ exchanger NCX1.1 measured in transfected HEK cells. Biophysical journal 67 11916852
2009 Anoxia-induced NF-kappaB-dependent upregulation of NCX1 contributes to Ca2+ refilling into endoplasmic reticulum in cortical neurons. Stroke 66 19164785
2011 NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke 62 21293012
2014 Endoplasmic reticulum refilling and mitochondrial calcium extrusion promoted in neurons by NCX1 and NCX3 in ischemic preconditioning are determinant for neuroprotection. Cell death and differentiation 59 24632945
2014 MicroRNA-103-1 selectively downregulates brain NCX1 and its inhibition by anti-miRNA ameliorates stroke damage and neurological deficits. Molecular therapy : the journal of the American Society of Gene Therapy 59 24954474
2000 Functional differences between cardiac and renal isoforms of the rat Na+-Ca2+ exchanger NCX1 expressed in Xenopus oocytes. The Journal of physiology 59 11118492
2009 Kinetic and equilibrium properties of regulatory calcium sensors of NCX1 protein. The Journal of biological chemistry 58 19141619
2002 Sodium/calcium exchanger subtypes NCX1, NCX2 and NCX3 show cell-specific expression in rat hippocampus cultures. Brain research. Molecular brain research 57 12425943
2013 The topology of the cardiac Na⁺/Ca²⁺ exchanger, NCX1. Journal of molecular and cellular cardiology 52 23376057
1997 Cloning of cardiac, kidney, and brain promoters of the feline ncx1 gene. The Journal of biological chemistry 51 9111065
2011 NCX1 and NCX3: two new effectors of delayed preconditioning in brain ischemia. Neurobiology of disease 50 22036625
2018 The NCX1/TRPC6 Complex Mediates TGFβ-Driven Migration and Invasion of Human Hepatocellular Carcinoma Cells. Cancer research 49 29500176
2018 Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis. Experimental & molecular medicine 49 29735991
2016 Endothelial Cells Can Regulate Smooth Muscle Cells in Contractile Phenotype through the miR-206/ARF6&NCX1/Exosome Axis. PloS one 49 27031991
2013 The cardiac sodium-calcium exchanger NCX1 is a key player in the initiation and maintenance of a stable heart rhythm. Cardiovascular research 48 23761399
2002 Plasma membrane Ca2+-ATPase and NCX1 Na+/Ca2+ exchanger expression in distal convoluted tubule cells. American journal of physiology. Renal physiology 48 12060584
2013 An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart. Cardiovascular research 46 23436819
2007 Mitochondrial localization of Na+/Ca2+ exchangers NCX1-3 in neurons and astrocytes of adult rat brain in situ. Pharmacological research 46 18024055
2007 The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway. Molecular pharmacology 46 18079274
2017 Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women. Biology of sex differences 45 28807015
2023 Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke. Science signaling 42 37279286
2015 Anoctamin-6 controls bone mineralization by activating the calcium transporter NCX1. The Journal of biological chemistry 42 25589784
1996 The organization of the human gene NCX1 encoding the sodium-calcium exchanger. Genomics 42 8921376
2017 Coupling between the TRPC3 ion channel and the NCX1 transporter contributed to VEGF-induced ERK1/2 activation and angiogenesis in human primary endothelial cells. Cellular signalling 41 28535874
2018 LncRNA SLC8A1-AS1 protects against myocardial damage through activation of cGMP-PKG signaling pathway by inhibiting SLC8A1 in mice models of myocardial infarction. Journal of cellular physiology 40 30378115
2016 Genetic Variation in the SLC8A1 Calcium Signaling Pathway Is Associated With Susceptibility to Kawasaki Disease and Coronary Artery Abnormalities. Circulation. Cardiovascular genetics 40 27879314
2007 ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and brain ischemia. Annals of the New York Academy of Sciences 40 17446481
2002 Expression of Na(+)/Ca(2+) exchanger isoforms (NCX1 and NCX3) and plasma membrane Ca(2+) ATPase during osteoblast differentiation. Journal of cellular biochemistry 40 11813267
2012 NCX1 is a new rest target gene: role in cerebral ischemia. Neurobiology of disease 39 23069678
2018 NCX1 and NCX3 as potential factors contributing to neurodegeneration and neuroinflammation in the A53T transgenic mouse model of Parkinson's Disease. Cell death & disease 38 29941946
2014 Down-Regulation of SLC8A1 as a Putative Apoptosis Evasion Mechanism by Modulation of Calcium Levels in Penile Carcinoma. The Journal of urology 38 25481039
2011 High levels of synaptosomal Na(+)-Ca(2+) exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer's disease. Cell calcium 37 21382638
2009 beta-Adrenergic receptor stimulated Ncx1 upregulation is mediated via a CaMKII/AP-1 signaling pathway in adult cardiomyocytes. Journal of molecular and cellular cardiology 37 19945464
2002 The molecular determinants of ionic regulatory differences between brain and kidney Na+/Ca2+ exchanger (NCX1) isoforms. The Journal of biological chemistry 37 12118014
1999 Cardiac expression of the Na(+)/Ca(2+) exchanger NCX1 is GATA factor dependent. The American journal of physiology 36 10409212
2004 Effects of SEA0400 on mutant NCX1.1 Na+-Ca2+ exchangers with altered ionic regulation. Molecular pharmacology 35 14978259
2014 Na+ dysregulation coupled with Ca2+ entry through NCX1 promotes muscular dystrophy in mice. Molecular and cellular biology 34 24662047
2012 Physical and functional interaction of NCX1 and EAAC1 transporters leading to glutamate-enhanced ATP production in brain mitochondria. PloS one 34 22479505
2018 Deficiency of PKD2L1 (TRPP3) Exacerbates Pathological Cardiac Hypertrophy by Augmenting NCX1-Mediated Mitochondrial Calcium Overload. Cell reports 33 30089272
2006 Cells expressing unique Na+/Ca2+ exchange (NCX1) splice variants exhibit different susceptibilities to Ca2+ overload. American journal of physiology. Heart and circulatory physiology 33 16399865
1999 Chimeric analysis of Na(+)/Ca(2+) exchangers NCX1 and NCX3 reveals structural domains important for differential sensitivity to external Ni(2+) or Li(+). The Journal of biological chemistry 33 10438478
2012 Nanomolar ouabain increases NCX1 expression and enhances Ca2+ signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance? American journal of physiology. Heart and circulatory physiology 31 22842068
2000 Physiological functions of the regulatory domains of the cardiac Na(+)/Ca(2+) exchanger NCX1. American journal of physiology. Cell physiology 30 10913006
2001 NCX1 Na/Ca exchanger splice variants in pancreatic islet cells. The Journal of endocrinology 29 11241183
2012 ERK1/2, p38, and JNK regulate the expression and the activity of the three isoforms of the Na+ /Ca2+ exchanger, NCX1, NCX2, and NCX3, in neuronal PC12 cells. Journal of neurochemistry 28 22708976
2016 Induced NCX1 overexpression attenuates pressure overload-induced pathological cardiac remodelling. Cardiovascular research 27 27229460
2016 The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux. Oncotarget 27 27275542
2011 CaMKIIδB mediates aberrant NCX1 expression and the imbalance of NCX1/SERCA in transverse aortic constriction-induced failing heart. PloS one 27 21931829
2002 Functional regulation of alternatively spliced Na+/Ca2+ exchanger (NCX1) isoforms. Annals of the New York Academy of Sciences 27 12502560
2014 Involvement of the Na+/Ca2+ exchanger isoform 1 (NCX1) in neuronal growth factor (NGF)-induced neuronal differentiation through Ca2+-dependent Akt phosphorylation. The Journal of biological chemistry 26 25416782
2009 Molecular pharmacology of the amiloride analog 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-n-[[(2,4-dimethylbenzyl)-amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) as a pan inhibitor of the Na+-Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in stably transfected cells. The Journal of pharmacology and experimental therapeutics 26 19602550
2001 A distant upstream region of the rat multipartite Na(+)-Ca(2+) exchanger NCX1 gene promoter is sufficient to confer cardiac-specific expression. Mechanisms of development 26 11731239
2003 Partial rescue of the Na+-Ca2+ exchanger (NCX1) knock-out mouse by transgenic expression of NCX1. Experimental & molecular medicine 25 12754417
1998 Cloning of the multipartite promoter of the sodium-calcium exchanger gene NCX1 and characterization of its activity in vascular smooth muscle cells. The Journal of biological chemistry 25 9516469
2015 Calmodulin Interacts with the Sodium/Calcium Exchanger NCX1 to Regulate Activity. PloS one 24 26421717
2008 Membrane targeting and coupling of NHE1-integrinalphaIIbbeta3-NCX1 by lipid rafts following integrin-ligand interactions trigger Ca2+ oscillations. The Journal of biological chemistry 24 18996841
2023 Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400. The EMBO journal 22 38177313
2011 Distinct expression of the calcium exchangers, NCKX3 and NCX1, and their regulation by steroid in the human endometrium during the menstrual cycle. Reproductive sciences (Thousand Oaks, Calif.) 22 21321244
2009 A Na+/Ca2+ exchanger isoform, NCX1, is involved in retinal cell death after N-methyl-D-aspartate injection and ischemia-reperfusion. Journal of neuroscience research 22 18855935
2018 The inhibitory effect of rosmarinic acid on overexpression of NCX1 and stretch- induced arrhythmias after acute myocardial infarction in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29710544
2020 Regulation of NCX1 by palmitoylation. Cell calcium 20 31935590
2020 Circ-SLC8A1 regulates osteoporosis through blocking the inhibitory effect of miR-516b-5p on AKAP2 expression. The journal of gene medicine 20 32830397
2015 Evidence for a non-canonical role of HDAC5 in regulation of the cardiac Ncx1 and Bnp genes. Nucleic acids research 20 26704971
2002 Toward a topological model of the NCX1 exchanger. Annals of the New York Academy of Sciences 20 12502529
1999 Truncation of the C terminus of the rat brain Na(+)-Ca(2+) exchanger RBE-1 (NCX1.4) impairs surface expression of the protein. The Journal of biological chemistry 20 10455160
1998 NCX1 Na/Ca exchanger inhibition by antisense oligonucleotides in mouse distal convoluted tubule cells. Kidney international 20 9734614
2021 The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke. Cell death & disease 19 33931586
2006 Regulation of Ncx1 expression. Identification of regulatory elements mediating cardiac-specific expression and up-regulation. The Journal of biological chemistry 19 16966329
2024 Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1. Nature communications 18 38714663
2021 Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1. Cell calcium 18 33873072
2020 Transcriptional and epigenetic regulation of ncx1 and ncx3 in the brain. Cell calcium 18 32172011
2020 Gateways for Glutamate Neuroprotection in Parkinson's Disease (PD): Essential Role of EAAT3 and NCX1 Revealed in an In Vitro Model of PD. Cells 18 32899900
2016 Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway. Cancer letters 18 27108064
2010 Nitric oxide stimulates NCX1 and NCX2 but inhibits NCX3 isoform by three distinct molecular determinants. Molecular pharmacology 18 21159997
2009 Change in intracellular pH causes the toxic Ca2+ entry via NCX1 in neuron- and glia-derived cells. Cellular and molecular neurobiology 18 19830548
2022 Insulin-induced palmitoylation regulates the Cardiac Na+/Ca2+ exchanger NCX1. Cell calcium 17 35231700
2015 NCX1 Exchanger Cooperates with Calretinin to Confer Preconditioning-Induced Tolerance Against Cerebral Ischemia in the Striatum. Molecular neurobiology 17 25633096
2013 Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. PloS one 17 23990893
2007 What we know about the structure of NCX1 and how it relates to its function. Annals of the New York Academy of Sciences 17 17303833
2007 Phosphorylation and other conundrums of Na/Ca exchanger, NCX1. Annals of the New York Academy of Sciences 17 17446449
2003 Co-ordinated expression of 5-HT2C receptors with the NCX1 Na+/Ca2+ exchanger in histaminergic neurones. Journal of neurochemistry 17 14535948
2022 NCX1 coupled with TRPC1 to promote gastric cancer via Ca2+/AKT/β-catenin pathway. Oncogene 16 35882979
2013 Transcriptional pathways and potential therapeutic targets in the regulation of Ncx1 expression in cardiac hypertrophy and failure. Advances in experimental medicine and biology 16 23224875
2002 Role of sodium-calcium exchanger (Ncx1) in embryonic heart development: a transgenic rescue? Annals of the New York Academy of Sciences 16 12502569

Missed literature

Know a paper Affinage missed for SLC8A1? Flag it for the maintainers and the community.

No submissions yet.