Affinage

SLC30A3

Probable proton-coupled zinc antiporter SLC30A3 · UniProt Q99726

Length
388 aa
Mass
41.9 kDa
Annotated
2026-04-28
56 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC30A3 (ZnT3) is a six-transmembrane-domain H⁺/Zn²⁺ antiporter that loads zinc into synaptic vesicles of glutamatergic neurons, thereby establishing the pool of vesicular zinc released during neurotransmission (PMID:8962159, PMID:9990090, PMID:39474773). ZnT3 is targeted to synaptic vesicle membranes through selective interaction with the AP-3 adaptor complex and forms covalent dityrosine-linked oligomers (via Y372 and Y357) that regulate its vesicle targeting and transport capacity (PMID:14657250, PMID:19521526). Genetic ablation of ZnT3 completely eliminates histochemically reactive and mass-spectrometric vesicular zinc, abolishes activity-dependent presynaptic ERK1/2 MAPK signaling in hippocampal mossy fibers, and produces deficits in contextual discrimination and spatial working memory (PMID:9990090, PMID:17712179, PMID:21245308). SLC30A3 transcription is driven by Sp1 binding to GC-box elements—a process inhibited by mutant huntingtin—and is epigenetically repressed by HDAC1-mediated H3K27 deacetylation at its super-enhancer region (PMID:32944220, PMID:33715270).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Identification of a candidate synaptic vesicle zinc transporter resolved the long-standing question of how histochemically reactive zinc accumulates in presynaptic terminals.

    Evidence Molecular cloning of ZnT3 with immunohistochemistry matching Timm's zinc staining pattern in mouse brain

    PMID:8962159

    Open questions at the time
    • Transport activity not directly demonstrated at this stage
    • Necessity for vesicular zinc not established
  2. 1997 High

    Ultrastructural localization established that ZnT3 resides on the membranes of all clear synaptic vesicles in zinc-rich boutons, not on other organelles, placing it at the correct subcellular site to mediate vesicular zinc loading.

    Evidence Immuno-electron microscopy of mossy fiber boutons in mouse and monkey hippocampus

    PMID:9356509

    Open questions at the time
    • Functional transport not yet demonstrated
    • Mechanism of vesicle targeting unknown
  3. 1999 High

    Gene knockout proved that ZnT3 is both necessary and sufficient (in a dose-dependent manner) for all histochemically detectable vesicular zinc, ruling out redundant transporters.

    Evidence ZnT3 knockout and heterozygous mice analyzed by Timm's staining, synchrotron XRF, and Western blot

    PMID:9990090

    Open questions at the time
    • Behavioral consequences of vesicular zinc loss unknown
    • Molecular transport mechanism (antiporter vs. uniporter) unresolved
  4. 2000 High

    Using the ZnT3 knockout as an epistasis tool showed that seizure-induced toxic zinc accumulation in neurons derives from non-vesicular sources, reframing the role of vesicular zinc in excitotoxicity.

    Evidence Kainate seizure model in ZnT3 KO mice with fluorescent zinc imaging and CaEDTA chelation

    PMID:10807937

    Open questions at the time
    • Identity of non-vesicular zinc source not determined
    • Relevance to chronic neurodegeneration unclear
  5. 2003 High

    Discovery that ZnT3 is targeted to synaptic vesicles via selective binding to the AP-3 adaptor complex provided the first vesicle-sorting mechanism for a zinc transporter and explained its compartment-specific localization.

    Evidence Cell-free AP-3 binding assay, AP-3-null (mocha) mouse biochemistry, and immunoisolation of vesicle populations

    PMID:14657250

    Open questions at the time
    • Sorting signal motif on ZnT3 not mapped
    • Whether AP-3 interaction is direct or via an adaptor unclear
  6. 2005 High

    Co-targeting of ZnT3 and Vglut1 to the same vesicles with reciprocal enhancement of zinc and glutamate uptake revealed a functional coupling between vesicular zinc and glutamate loading.

    Evidence Deconvolution microscopy, subcellular fractionation, and functional transport assays in PC12 cells with AP-3 perturbation

    PMID:15860731

    Open questions at the time
    • Mechanism of reciprocal transport enhancement not defined
    • Whether coupling occurs in vivo not tested
  7. 2007 High

    Quantitative elemental analysis confirmed that ZnT3 controls the actual mass of zinc—not just histochemical stainability—in mossy fibers, validating prior qualitative staining methods.

    Evidence Microprobe synchrotron X-ray fluorescence in ZnT3 KO versus wild-type hippocampus

    PMID:17712179

    Open questions at the time
    • Zinc concentrations in individual vesicles not resolved
    • Stoichiometry of transport unknown
  8. 2009 High

    Identification of dityrosine-mediated covalent oligomerization (Y372, Y357) as a regulator of ZnT3 vesicle targeting and zinc transport capacity provided the first post-translational regulatory mechanism for this transporter.

    Evidence Site-directed mutagenesis with SDS-PAGE, vesicle targeting assay, and zinc toxicity resistance in PC12 cells

    PMID:19521526

    Open questions at the time
    • Oxidative enzyme catalyzing dityrosine bond formation not identified
    • In vivo relevance of oligomerization not tested
  9. 2011 High

    Linking vesicular zinc release to presynaptic ERK1/2 MAPK signaling and hippocampus-dependent memory established a downstream signaling pathway through which ZnT3 influences cognition.

    Evidence ZnT3 KO mice with phospho-ERK immunoassay, pharmacological zinc/MAPK blockade, and behavioral tasks (contextual discrimination, spatial working memory)

    PMID:21245308

    Open questions at the time
    • Direct zinc target upstream of ERK1/2 not identified
    • Whether zinc acts on presynaptic receptors or intracellularly unresolved
  10. 2013 Medium

    Biophysical characterization of ZnT3 metal-binding peptides identified a high-affinity N-terminal HHCH zinc-binding site with tetrahedral coordination, providing candidate residues for the transport or sensing mechanism.

    Evidence Potentiometric titration, UV-Vis, CD, EPR, NMR spectroscopy of synthetic peptide-metal complexes

    PMID:23839275

    Open questions at the time
    • Studies used peptide fragments, not full-length protein
    • Role of HHCH site in transport cycle not validated by mutagenesis in cells
  11. 2016 Medium

    Multiple lines of work expanded ZnT3's functional repertoire beyond mossy fibers: ZnT3 localizes to insulin secretory granules in beta cells and modulates insulin content, and ZnT3 knockdown sensitizes neuroblastoma cells to ER stress by preventing ERK1/2 activation.

    Evidence Immuno-gold EM in INS-1E cells with overexpression/secretion assays; siRNA knockdown in SH-SY5Y cells under tunicamycin with ERK1/2 phosphorylation readout

    PMID:26867900 PMID:27678294

    Open questions at the time
    • Physiological importance of ZnT3 in beta cells versus the canonical ZnT8 not delineated
    • ER stress protection mechanism downstream of ERK not resolved
  12. 2020 Medium

    Demonstration that mutant huntingtin reduces ZnT3 transcription by inhibiting Sp1 binding to the ZnT3 promoter provided a mechanistic link between Huntington's disease pathogenesis and vesicular zinc depletion.

    Evidence ChIP plus dual-luciferase reporter assay in BHK cells and N171-82Q HD transgenic mice, with Sp1 overexpression rescue

    PMID:32944220

    Open questions at the time
    • Whether ZnT3 restoration rescues HD phenotypes not tested
    • Other transcription factors controlling SLC30A3 expression not characterized
  13. 2021 Medium

    Identification of HDAC1-mediated H3K27 deacetylation at the SLC30A3 super-enhancer as an epigenetic silencing mechanism expanded understanding of how SLC30A3 is transcriptionally regulated, with functional consequences for MAPK-dependent apoptosis in glioblastoma cells.

    Evidence ChIP-seq in glioblastoma cells, overexpression/knockdown with in vitro and in vivo growth assays, MAPK pathway analysis

    PMID:33715270

    Open questions at the time
    • Relevance of this epigenetic mechanism to neuronal ZnT3 expression not examined
    • Whether MAPK-mediated apoptosis reflects canonical ZnT3 function unclear
  14. 2023 Medium

    Neuronal-specific ZnT3 knockout in a stroke model established that vesicular zinc released into extracellular fluid directly activates MMP-2, degrading tight junction proteins and disrupting the blood-brain barrier.

    Evidence Neuronal-specific ZnT3 KO mice with cerebral ischemia, extracellular zinc measurement, MMP-2 activity assay, tight junction protein analysis

    PMID:37962463

    Open questions at the time
    • Whether zinc activates MMP-2 by direct metal binding or indirect mechanism not fully resolved
    • Contribution relative to other MMP activators in stroke not quantified
  15. 2024 High

    Cryo-EM structures of ZnT3 (inward-facing) and the related ZnT4 (outward-facing) revealed the conformational cycle underlying H⁺/Zn²⁺ antiport, providing the first structural framework for the SLC30A3 transport mechanism.

    Evidence Cryo-electron microscopy of human ZnT3 and ZnT4

    PMID:39474773

    Open questions at the time
    • Only the inward-facing conformation was captured for ZnT3 itself
    • Substrate-bound transition states not resolved
    • Transport kinetics not measured
  16. 2025 Medium

    Discovery that ZnT3 physically interacts with TMEM163 and that both cooperatively regulate zinc efflux and neuronal apoptosis under ischemic conditions identified a new functional partner modulating ZnT3 activity.

    Evidence Co-immunoprecipitation, surface biotinylation, siRNA/overexpression with FluoZin-3 zinc measurement and TUNEL in primary hippocampal neurons under OGD

    PMID:41504061

    Open questions at the time
    • Reciprocal Co-IP and endogenous interaction not confirmed in brain tissue
    • Stoichiometry and interface of ZnT3–TMEM163 complex unknown
    • In vivo validation of cooperative zinc efflux pending

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the direct zinc sensor or receptor that transduces released vesicular zinc into ERK1/2 activation, the structural basis of ZnT3's transport cycle in substrate-bound states, and the physiological significance of ZnT3 outside the nervous system (e.g., pancreatic beta cells).
  • No direct zinc target upstream of presynaptic ERK identified
  • Outward-facing ZnT3 cryo-EM structure not yet captured
  • Physiological role of ZnT3 in beta cells versus ZnT8 not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140657 ATP-dependent activity 1
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005886 plasma membrane 2
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-112316 Neuronal System 3
Partners
AP3D1SP1TMEM163VGLUT1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ZnT3 (SLC30A3) was cloned and predicted to have six transmembrane domains with 52% amino acid identity to ZnT2; antibodies against its C-terminal tail produced staining matching Timm's histochemical zinc reaction in synaptic vesicle-rich regions, leading to the proposal that ZnT3 transports zinc into synaptic vesicles. Molecular cloning, Northern blot, RT-PCR, in situ hybridization, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 8962159
1997 ZnT3 protein was localized by electron microscopy to the membranes of all clear small round synaptic vesicles in mossy fiber boutons in mouse and monkey hippocampus, coinciding with Timm's-stainable zinc-containing vesicles. Electron microscopy immunolocalization, Timm's staining Proceedings of the National Academy of Sciences of the United States of America High 9356509
1999 Targeted disruption of the ZnT3 gene completely eliminated histochemically reactive vesicular zinc from mouse brain without altering mossy fiber bouton ultrastructure; mice heterozygous for ZnT3 had proportionally reduced ZnT3 protein and intermediate vesicular zinc, establishing that ZnT3 is required for zinc transport into synaptic vesicles and that vesicular zinc concentration is determined by ZnT3 abundance. Gene knockout, Timm's staining, immunohistochemistry, Western blot, synchrotron X-ray fluorescence Proceedings of the National Academy of Sciences of the United States of America High 9990090
2000 In ZnT3 knockout mice subjected to kainate seizures, zinc still accumulated in degenerating CA1/CA3 neurons (detectable by fluorescent zinc dye), demonstrating that the source of toxic zinc accumulation is not synaptic vesicles but other extracellular sources; CaEDTA injection into ventricles blocked this accumulation, indicating that extracellular zinc rise is the critical event. ZnT3 knockout model, kainate seizure induction, fluorescent zinc staining (MSO dye), CaEDTA chelation The Journal of neuroscience High 10807937
2003 ZnT3 cytosolic tail interacted selectively with the AP-3 adaptor complex in cell-free assays; pharmacological or genetic disruption of AP-3 specifically reduced ZnT3 (but not synaptophysin) targeting to synaptic-like microvesicles, and immunoisolation confirmed ZnT3 and synaptophysin reside in distinct vesicle subpopulations. ZnT3 content in synaptic vesicles was reduced in AP-3-deficient (mocha) neurons. Cell-free AP-3 binding assay, pharmacological disruption of vesicle biogenesis, immunoisolation, mocha (AP-3 null) mouse brain biochemistry, immunofluorescence Molecular biology of the cell High 14657250
2005 ZnT3 and the vesicular glutamate transporter Vglut1 are co-targeted to the same synaptic-like microvesicles via partly AP-3-dependent mechanisms; Vglut1 expression increased vesicular zinc uptake, and ZnT3 expression increased vesicular glutamate uptake in a zinc-dependent fashion, indicating functional coupling of their transport activities. Deconvolution microscopy, subcellular fractionation, whole-cell flow cytometry zinc uptake assay, pharmacological and genetic AP-3 perturbation Journal of cell science High 15860731
2007 Microprobe synchrotron X-ray fluorescence demonstrated that the 2-3 fold elevation of total elemental zinc normally present in hippocampal mossy fibers is absent in ZnT3 knockout mice, confirming that ZnT3 controls the actual mass (not just histochemical stainability) of zinc in synaptic vesicles. Microprobe synchrotron X-ray fluorescence (quantitative elemental analysis), ZnT3 knockout mice The journal of histochemistry and cytochemistry High 17712179
2009 ZnT3 forms covalent homo-oligomers via intermolecular dityrosine bonds; mutagenesis identified Y372 and Y357 as critical residues. Y372F mutation prevented oligomerization, reduced ZnT3 targeting to synaptic-like microvesicles, and decreased resistance to zinc toxicity. Y357F acted as a gain-of-function mutant with increased oligomerization, vesicle targeting, and zinc toxicity resistance, establishing that dityrosine dimerization regulates ZnT3 subcellular localization and zinc transport capacity. Site-directed mutagenesis, SDS-PAGE under non-reducing conditions, vesicle targeting assay, zinc toxicity resistance assay in PC12 cells PloS one High 19521526
2009 siRNA-mediated knockdown of ZnT3 in INS-1E pancreatic beta cells decreased insulin expression and secretion; ZnT3 knockout mice showed higher glucose levels after streptozotocin-induced beta-cell stress. ZnT3 expression in beta cells was regulated by glucose concentration and zinc chelation. siRNA knockdown, ELISA insulin assay, in vivo streptozotocin model with ZnT3 KO mice, Western blot, immunohistochemistry PloS one Medium 19492079
2011 ZnT3 knockout mice have reduced Erk1/2 MAPK activation in hippocampal mossy fiber terminals and disinhibited zinc-sensitive MAPK tyrosine phosphatase activity. Activity-dependent vesicular zinc exocytosis is required for presynaptic MAPK and phosphatase regulation. ZnT3KO mice show complete deficits in contextual discrimination and spatial working memory; local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. ZnT3 KO mice, phospho-ERK immunoassay, pharmacological MAPK/zinc blockade, behavioral tasks (contextual discrimination, spatial working memory) Proceedings of the National Academy of Sciences of the United States of America High 21245308
2012 In vascular smooth muscle cells, Angiotensin II-induced senescence requires zinc and downregulation of ZnT3 and ZnT10. Overexpression of ZnT3 decreased reactive oxygen species and prevented senescence. ZnT3 and ZnT10 downregulation by siRNA increases ROS and downregulates catalase by a post-transcriptional mechanism mediated by decreased ERK1/2 phosphorylation. Overexpression, siRNA knockdown, ROS assay, NADPH oxidase activity assay, AKT/Akt phosphorylation assay, catalase assay in vascular smooth muscle cells PloS one Medium 22427991
2013 Potentiometric and spectroscopic (UV-Vis, CD, EPR, NMR) analyses of peptides mimicking ZnT3 metal-binding sequences identified a high-affinity zinc-binding site at the conserved N-terminal -HHCH- sequence (modeled by peptide L3), which binds zinc with 3-4 orders of magnitude higher stability than the His-rich intracellular loop, with {3N(im),S(-)} tetrahedral coordination, suggesting this site is involved in zinc sensing or translocation. Potentiometric titration, UV-Vis, CD, EPR, NMR spectroscopy of synthetic peptide-metal complexes Dalton transactions Medium 23839275
2016 SLC30A3 knockdown in neuroblastoma cells (SH-SY5Y) reduced cell viability and increased cleaved caspase-3 under ER stress (tunicamycin treatment); SLC30A3 KD abolished the ERK1/2 phosphorylation increase normally induced by tunicamycin, placing SLC30A3 upstream of ERK1/2 activation in the cellular defense against ER stress. siRNA knockdown, cell viability assay, cleaved caspase-3 Western blot, ERK1/2 phosphorylation assay under tunicamycin treatment Biochemical and biophysical research communications Medium 27678294
2016 ZnT3 gene deletion reduced motor deficits and neuropathological changes (demyelination, immune cell infiltration, BBB disruption) in a MOG-induced EAE multiple sclerosis model; ZnT3 deletion inhibited EAE-associated MMP-9 activation and formation of aberrant synaptic zinc patches. ZnT3 KO mice, EAE induction, clinical scoring, immunohistochemistry, MMP-9 activity assay, BBB permeability assay Neurobiology of disease Medium 27370228
2020 Mutant huntingtin inhibits binding of the transcription factor Sp1 to GC boxes in the ZnT3 promoter, reducing ZnT3 transcription. Sp1 overexpression ameliorated mutant huntingtin-induced ZnT3 downregulation. This was demonstrated by dual-luciferase reporter gene assay and chromatin immunoprecipitation in HD transgenic mice and BHK cells expressing mutant huntingtin. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), Western blot, RT-PCR, autometallography in N171-82Q HD transgenic mice Cell & bioscience Medium 32944220
2021 HDAC1, overexpressed in glioblastoma, inhibits SLC30A3 expression by promoting H3K27ac deacetylation of the super enhancer region of SLC30A3. SLC30A3 overexpression activates the MAPK signaling pathway to promote apoptosis of GBM cells and inhibits growth and metastasis in vitro and in vivo. ChIP-seq, GEO microarray analysis, overexpression/knockdown functional assays in vitro and in vivo, MAPK pathway analysis IUBMB life Medium 33715270
2024 Cryo-EM structures of human ZnT3 (inward-facing conformation) and ZnT4 (outward-facing conformation) were determined; combining these structures revealed the conformational changes within the transmembrane domain during Zn2+ transport, consistent with a H+/Zn2+ antiporter mechanism. Cryo-electron microscopy structural determination of human ZnT3 and ZnT4 FEBS letters High 39474773
2024 WFS1 regulates ZnT3 expression; in neural progenitor cells derived from hESCs, WFS1 deficiency caused upregulation of ZnT3 and dysregulated Zn2+ homeostasis leading to apoptosis. Riluzole treatment regulated ZnT3 expression to restore zinc homeostasis and protect NPCs from lipotoxicity-induced death. hESC neural differentiation, WFS1 knockout, ZnT3 expression analysis, apoptosis assay, riluzole pharmacological intervention Advanced science Medium 39258564
2023 Neuronal-specific ZnT3 knockout mice showed markedly reduced extracellular fluid zinc levels and reduced BBB permeability after cerebral ischemia; elevated extracellular zinc (from ZnT3-mediated vesicular release) directly bound to and activated MMP-2 in extracellular fluid, leading to degradation of tight junction proteins and BBB disruption. Neuronal-specific ZnT3 KO mice, rat stroke model, extracellular zinc measurement, BBB permeability assay, MMP-2 activity assay, tight junction protein analysis Aging and disease Medium 37962463
2024 ZnT3 knockout mice showed reduced hippocampal and cortical zinc, decreased density of mature dendritic spines, reduced expression of GLUT3, GLUT4, and insulin receptor in hippocampal synaptosomes, and reduced AKT expression and insulin-induced AKT phosphorylation, linking ZnT3-dependent zinc homeostasis to insulin signaling and synaptic plasticity. ZnT3 KO mice, Golgi-Cox staining of dendritic spines, Western blot for glucose transporters and insulin signaling components in synaptosomes, behavioral testing Frontiers in molecular neuroscience Medium 38807922
2025 ZnT3 physically interacts with TMEM163 (shown by co-immunoprecipitation); under oxygen-glucose deprivation, both proteins translocate from the cell membrane to the cytoplasm, and their overexpression exacerbates extracellular zinc overload and neuronal apoptosis, while silencing attenuates zinc efflux and neuronal damage, demonstrating cooperative regulation of zinc homeostasis. Co-immunoprecipitation, cell surface biotinylation for localization, siRNA silencing, plasmid overexpression, FluoZin-3 zinc measurement, MTT viability assay, TUNEL staining in primary hippocampal neurons under OGD Frontiers in bioscience Medium 41504061
2020 miR-5572 is elevated in sporadic ALS spinal cords and was predicted and validated to target SLC30A3 mRNA, providing a post-transcriptional mechanism for reduced ZnT3 levels in sALS. Microarray, real-time RT-PCR, TargetScan prediction, functional validation of miR-5572 targeting SLC30A3 International journal of molecular sciences Low 32599739
2016 In pancreatic INS-1E beta cells, ZnT3 co-localizes with insulin in secretory granules near the plasma membrane (shown by immuno-gold electron microscopy); ZnT3 overexpression decreased insulin content and secretion but improved cell survival, while reducing ZnT8 mRNA expression, suggesting transcriptional co-regulation between ZnT3 and ZnT8. Immuno-gold electron microscopy, overexpression, insulin ELISA, cell viability assay, qRT-PCR Biometals Medium 26867900

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 ZnT-3, a putative transporter of zinc into synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America 590 8962159
1999 Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proceedings of the National Academy of Sciences of the United States of America 457 9990090
1997 Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. Proceedings of the National Academy of Sciences of the United States of America 302 9356509
2000 Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures: evidence against synaptic vesicle origin. The Journal of neuroscience : the official journal of the Society for Neuroscience 173 10807937
2011 Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory. Proceedings of the National Academy of Sciences of the United States of America 144 21245308
2014 Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment. Neurobiology of aging 105 25104558
2003 The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation. Molecular biology of the cell 100 14657250
2007 Evidence that the ZNT3 protein controls the total amount of elemental zinc in synaptic vesicles. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 98 17712179
2012 Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PloS one 79 22427991
2005 Vglut1 and ZnT3 co-targeting mechanisms regulate vesicular zinc stores in PC12 cells. Journal of cell science 74 15860731
2009 SLC30A3 responds to glucose- and zinc variations in beta-cells and is critical for insulin production and in vivo glucose-metabolism during beta-cell stress. PloS one 67 19492079
2009 ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain. Molecular neurodegeneration 54 20030848
2000 Deficiencies of hippocampal Zn and ZnT3 accelerate brain aging of Rat. Biochemical and biophysical research communications 48 11118316
2009 SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its subcellular localization and metal transport capacity. PloS one 45 19521526
2014 Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis. Journal of neuroscience research 44 25284286
2002 Developmental expression of ZnT3 in mouse brain: correlation between the vesicular zinc transporter protein and chelatable vesicular zinc (CVZ) cells. Glial and neuronal CVZ cells interact. Molecular and cellular neurosciences 36 12401442
2011 ZnT3: a zinc transporter active in several organs. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 35 21866305
2008 ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats. Toxicology letters 29 19059322
2004 Localization of zinc transporter-3 (ZnT-3) in mouse retina. Vision research 28 15535999
2007 Zinc distribution and expression pattern of ZnT3 in mouse brain. Biological trace element research 27 17916939
2010 siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 26 21208276
2020 Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington's disease transgenic mouse. Cell & bioscience 22 32944220
2016 Common variants in the chromosome 2p23 region containing the SLC30A3 (ZnT3) gene are associated with schizophrenia in female but not male individuals in a large collection of European samples. Psychiatry research 21 27750116
2019 Involvement of the synapse-specific zinc transporter ZnT3 in cadmium-induced hippocampal neurotoxicity. Journal of cellular physiology 19 30714133
2016 Zinc transporter 3 (ZnT3) gene deletion reduces spinal cord white matter damage and motor deficits in a murine MOG-induced multiple sclerosis model. Neurobiology of disease 19 27370228
2010 Elevation of zinc transporter ZnT3 protein in the cerebellar cortex of the AbetaPP/PS1 transgenic mouse. Journal of Alzheimer's disease : JAD 19 20164588
2021 Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma. IUBMB life 18 33715270
2020 Increased Cerebrospinal Fluid Concentration of ZnT3 Is Associated with Cognitive Impairment in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 17 32925049
2019 Effects of social defeat stress and fluoxetine treatment on neurogenesis and behavior in mice that lack zinc transporter 3 (ZnT3) and vesicular zinc. Hippocampus 15 31821659
2016 The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 15 26867900
2017 ZnT3 Gene Deletion Reduces Colchicine-Induced Dentate Granule Cell Degeneration. International journal of molecular sciences 14 29048371
2016 Protective roles of SLC30A3 against endoplasmic reticulum stress via ERK1/2 activation. Biochemical and biophysical research communications 14 27678294
2014 SLC30A3 and SEP15 gene polymorphisms influence the serum concentrations of zinc and selenium in mature adults. Nutrition research (New York, N.Y.) 14 25249019
2017 Leptin treatment prevents long-term abnormalities in cognition, seizure threshold, hippocampal mossy fiber sprouting and ZnT3/CB-D28k expression in a rat developmental "twist" seizure model. Epilepsy research 13 29287786
2016 Zinc Transporter 3 (Znt3) as an Active Substance in the Enteric Nervous System of the Porcine Esophagus. Journal of molecular neuroscience : MN 13 27796869
2017 Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or neuromodulators in the enteric nervous system of the porcine esophagus. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 12 28417221
2013 The effects of interactions between selenium and zinc serum concentration and SEP15 and SLC30A3 gene polymorphisms on memory scores in a population of mature and elderly adults. Genes & nutrition 12 24338343
2020 MicroRNA-5572 Is a Novel MicroRNA-Regulating SLC30A3 in Sporadic Amyotrophic Lateral Sclerosis. International journal of molecular sciences 11 32599739
2012 Neurochemical characterization of zinc transporter 3-like immunoreactive (ZnT3(+)) neurons in the intramural ganglia of the porcine duodenum. Journal of molecular neuroscience : MN 11 22791190
2019 Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc. Behavioural brain research 8 31689442
2005 Adrenalectomy-induced ZnT3 downregulation in mouse hippocampus is followed by vesicular zinc depletion. Neuroscience letters 8 15755519
2024 The WFS1-ZnT3-Zn2+ Axis Regulates the Vicious Cycle of Obesity and Depression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39258564
2023 Neuronal Zinc Transporter ZnT3 Modulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption. Aging and disease 7 37962463
2020 The Expression of ZnT3 and GFAP Is Potentiated in the Hippocampus of Drug-Resistant Epileptic Rats Induced by Amygdala Kindling. Neuroimmunomodulation 6 33161399
2013 A comparative study on the possible zinc binding sites of the human ZnT3 zinc transporter protein. Dalton transactions (Cambridge, England : 2003) 6 23839275
2024 Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms. FEBS letters 5 39474773
2024 Genetic deletion of zinc transporter ZnT3 induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism. Frontiers in molecular neuroscience 4 38807922
2022 Variants in the zinc transporter-3 encoding gene (SLC30A3) in schizophrenia and bipolar disorder: Effects on brain glutamate-A pilot study. Frontiers in psychiatry 4 36203844
2019 Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell-deficient mice. The European journal of neuroscience 4 31502721
2018 Alterations in the Neurobehavioral Phenotype and ZnT3/CB-D28k Expression in the Cerebral Cortex Following Lithium-Pilocarpine-Induced Status Epilepticus: the Ameliorative Effect of Leptin. Biological trace element research 3 29687372
2024 Zinc transporter ZnT3/Slc30a3 has a potential role in zinc ion influx in mouse oocytes. The Journal of reproduction and development 2 39048372
2025 Ginsenoside Rb1 combined with Lycium barbarum polysaccharide alleviate the Tripterygium wilfordii polyglycoside-induced oligoasthenozoospermia in mice by inhibiting ZnT3-mediated oxidative stress response. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 1 40233591
2025 SLC30A3 as a Zinc Transporter-Related Biomarker and Potential Therapeutic Target in Alzheimer's Disease. Genes 1 41300833
2023 A preliminary investigation of the regulatory effect of acupuncture on hippocampal circHDAC2/miR-3065/SLC30A3 axis in CIRI rats. Zhen ci yan jiu = Acupuncture research 1 38146241
2025 ZnT3-TMEM163 Mediates Zinc Homeostasis Imbalance Induced Neurodegeneration in Hippocampus. Frontiers in bioscience (Landmark edition) 0 41504061
2002 [Cloning of ZnT3 cDNA and expression of ZnT3 mRNA in mice]. Wei sheng yan jiu = Journal of hygiene research 0 12561542