Affinage

SLC30A1

Proton-coupled zinc antiporter SLC30A1 · UniProt Q9Y6M5

Length
507 aa
Mass
55.3 kDa
Annotated
2026-04-28
81 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC30A1 (ZnT1) is the principal plasma membrane zinc exporter, essential for systemic zinc homeostasis through basolateral efflux in intestinal enterocytes and for cytosolic zinc buffering in virtually all cell types. Its transmembrane domain mediates Zn²⁺/H⁺ antiport (or Zn²⁺/Ca²⁺ exchange in neurons), with His43 in TM helix II critical for zinc selectivity as revealed by cryo-EM structure and mutagenesis, while a structurally independent C-terminal domain inhibits L-type calcium channels and activates Raf-1/ERK signaling to enhance T-type calcium channel surface expression (PMID:28091657, PMID:39422023, PMID:22572848). ZnT1 is transcriptionally induced by zinc through MTF-1 binding to metal-response elements in its promoter, and post-translationally regulated by zinc-dependent endocytosis and proteasomal/lysosomal degradation under zinc-deficient conditions (PMID:10952993, PMID:31471319). Beyond ion transport, ZnT1 physically associates with GluN2A/NMDA receptor subunits to generate postsynaptic zinc microdomains that tonically inhibit NMDAR currents, regulates endosomal zinc to control TLR4 and PD-L1 surface expression in macrophages, and is required for NF-κB–dependent nitric oxide production and intracellular bacterial killing (PMID:32937457, PMID:37816045, PMID:39475776). Somatic in-frame deletions near the zinc-binding site cause pathological Na⁺ influx and autonomous aldosterone production in aldosterone-producing adenomas (PMID:37709865).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Establishing where ZnT1 acts: localization to the basolateral membrane of enterocytes resolved how dietary zinc exits absorptive cells into the circulation, defining ZnT1 as an efflux transporter rather than an uptake channel.

    Evidence Immunofluorescence and Western blot in rat intestine with dietary zinc manipulation

    PMID:9560190

    Open questions at the time
    • Mechanism of transport (ion coupling) unknown
    • No structural information
    • No loss-of-function in vivo
  2. 2000 High

    Identifying the transcriptional circuit: MTF-1 was shown to directly bind metal-response elements in the ZnT1 promoter and to be required for both basal and zinc-induced ZnT1 expression, establishing the feedback loop whereby zinc induces its own export machinery.

    Evidence EMSA, MTF-1 knockout fibroblasts, and transgenic mice with dietary zinc manipulation

    PMID:10952993

    Open questions at the time
    • Post-translational regulation not yet explored
    • Other transcription factors potentially involved not tested
  3. 2000 High

    Demonstrating neuroprotective zinc efflux: overexpression of ZnT1 enhanced zinc efflux and protected neurons from zinc toxicity, while dominant-negative ZnT1 increased vulnerability, linking ZnT1 activity to neuronal survival via L-type calcium channel-mediated zinc entry.

    Evidence Gain- and loss-of-function stable PC12 cell lines with zinc efflux and viability assays

    PMID:11119691

    Open questions at the time
    • Whether ZnT1 directly interacts with L-type channels or acts indirectly was unclear
    • Mechanism of dominant-negative action not defined
  4. 2004 Medium

    Discovering ZnT1's channel-modulatory function: ZnT1 was found to inhibit zinc permeation through L-type calcium channels independently of altering channel expression, revealing a second function beyond zinc efflux.

    Evidence Fluorescent zinc influx measurements in HEK293 and PC-12 cells co-expressing ZnT1 with LTCC

    PMID:15378655 PMID:15451416

    Open questions at the time
    • Whether inhibition is direct (physical interaction) or indirect was unresolved
    • No domain mapping
  5. 2006 High

    Validating LTCC inhibition in native cells: siRNA knockdown in cortical neurons and overexpression/knockdown in cardiomyocytes confirmed that endogenous ZnT1 inhibits L-type calcium channel currents, with ~4-fold increases in Ca²⁺/Zn²⁺ influx upon ZnT1 silencing.

    Evidence siRNA in primary neurons and cardiomyocytes; Xenopus oocyte electrophysiology; rapid pacing in vivo

    PMID:16741752 PMID:17196651

    Open questions at the time
    • Direct physical interaction with LTCC subunits not demonstrated
    • Structural basis of inhibition unknown
  6. 2009 High

    Confirming evolutionary conservation: Drosophila ZnT1 localized basolaterally in enterocytes and was required for zinc absorption; human ZnT1 (but not ZnT4 or ZnT7) rescued the fly phenotype, validating a conserved intestinal zinc export mechanism.

    Evidence Gut-specific RNAi in Drosophila with cross-species rescue by human ZnT1

    PMID:19325039

    Open questions at the time
    • Mammalian intestinal knockout not yet performed
    • Transport mechanism (ion coupling) still unknown
  7. 2011 High

    Identifying a signaling scaffold function: ZnT1's C-terminal domain was shown to interact with Raf-1 kinase and activate ERK, protecting cardiomyocytes from ischemia-reperfusion injury independently of zinc transport.

    Evidence C-terminal domain constructs, MEK inhibitor epistasis, LDH/caspase assays in HL-1 cells and isolated rat hearts

    PMID:22193398

    Open questions at the time
    • Direct binding site on Raf-1 not mapped
    • Physiological relevance in vivo not tested with conditional KO
  8. 2012 High

    Linking Ras-ERK to T-type channel regulation: ZnT1 was shown to enhance T-type calcium channel (CaV3.1/3.2) surface expression through Ras-ERK signaling, establishing ZnT1 as a hub connecting L-type channel inhibition and T-type channel activation.

    Evidence Xenopus oocyte electrophysiology; CHO cell surface biotinylation; TIRF; dominant-negative Raf-1 and MEK inhibitor

    PMID:22572848

    Open questions at the time
    • In vivo cardiac electrophysiology consequences not tested
    • Whether LTCC β-subunit competes with Raf-1 for ZnT1 binding not yet known
  9. 2014 High

    Defining the transport mechanism: ZnT1 was demonstrated to function as a Zn²⁺/H⁺ exchanger, with mutagenesis of two residues in the predicted zinc-binding domain abolishing both transport and zinc resistance.

    Evidence FluoZin-3/Fura-2 imaging in HEK293T; site-directed mutagenesis; pH and Na⁺ substitution experiments

    PMID:24951051

    Open questions at the time
    • No direct structural data for human ZnT1
    • Whether H⁺ coupling is universal or cell-type-specific unclear
  10. 2017 High

    Separating transport from channel modulation: domain dissection proved that zinc transport (transmembrane domain) and LTCC inhibition (C-terminal domain) are structurally and functionally independent — transport-dead mutants still inhibited LTCC, and the CTD alone sufficed.

    Evidence Site-directed mutagenesis of TM zinc-binding residues; CTD truncation; electrophysiology in oocytes and HEK cells

    PMID:28091657

    Open questions at the time
    • Structural basis of CTD–LTCC interaction not resolved
    • Whether CTD also mediates other protein interactions not systematically tested
  11. 2019 High

    Revealing post-translational regulation: ZnT1 was found to accumulate at the plasma membrane under zinc sufficiency but undergo endocytosis and proteasomal/lysosomal degradation under zinc deficiency, with N-glycosylation at Asn299 modulating protein stability.

    Evidence Endocytosis/degradation pathway inhibitors; N299 mutagenesis; zinc resistance assay

    PMID:31471319

    Open questions at the time
    • E3 ligase or sorting signals for endocytosis not identified
    • Whether zinc directly triggers conformational change for membrane retention unknown
  12. 2020 High

    Establishing a synaptic signaling role: ZnT1 was shown to physically associate with GluN2A at the postsynapse, creating a zinc microdomain that tonically inhibits NMDA receptors; disrupting this interaction with a cell-permeant peptide abolished synaptic zinc-dependent NMDAR inhibition.

    Evidence Cell-permeant peptide disrupting ZnT1-GluN2A; electrophysiology at dorsal cochlear nucleus synapses; intracellular zinc chelation

    PMID:32937457

    Open questions at the time
    • Binding interface between ZnT1 and GluN2A not structurally resolved
    • Generalizability across synapse types not fully established
  13. 2021 High

    Discovering alternative ion coupling in neurons: in cortical neurons, ZnT1 was shown to function as a Zn²⁺/Ca²⁺ exchanger rather than Zn²⁺/H⁺, with extracellular Ca²⁺ required for ZnT1-dependent Zn²⁺ efflux, revealing cell-type-specific transport mechanisms.

    Evidence AAV-shRNA knockdown; dual FluoZin-3/GCaMP6 imaging; H⁺ gradient and Ca²⁺ removal experiments in primary cortical neurons

    PMID:34871934

    Open questions at the time
    • Structural basis for Ca²⁺ vs H⁺ coupling selectivity unknown
    • Whether Zn²⁺/Ca²⁺ exchange occurs in non-neuronal cells not tested
  14. 2023 High

    Connecting ZnT1 mutations to disease: somatic in-frame deletions in SLC30A1 near the zinc-binding site (His43/Asp47) were found to cause pathological Na⁺ influx and autonomous aldosterone production, identifying ZnT1 as a driver of aldosterone-producing adenomas.

    Evidence Sequencing of APAs; inducible expression of SLC30A1Δ51_57del; Na⁺ current, Ca²⁺ imaging, CYP11B2 and aldosterone measurement in adrenal cells

    PMID:37709865

    Open questions at the time
    • Whether mutant ZnT1 conducts Na⁺ directly or indirectly through conformational change is unresolved
    • Prevalence across APA cohorts not fully defined
  15. 2023 High

    Revealing an immune regulatory function: myeloid-specific ZnT1 knockout showed that ZnT1 controls endosomal zinc to regulate TLR4 and PD-L1 endocytic turnover, and separately that ZnT1 zinc export is required for NF-κB activation, NO production, and intracellular Salmonella killing.

    Evidence Lyz2-Cre conditional KO mice; flow cytometry; liver tumor model; Salmonella infection; NF-κB and NO assays

    PMID:37816045 PMID:39475776

    Open questions at the time
    • Whether endosomal vs plasma membrane ZnT1 pools serve distinct functions in macrophages is unclear
    • Downstream zinc-sensing mechanism activating NF-κB not identified
  16. 2024 High

    Solving the structure and confirming essentiality: cryo-EM structure of ZnT1 combined with His43 mutagenesis revealed a unique zinc transport mechanism within the SLC30 family, and intestinal-specific knockout proved ZnT1 is essential for systemic zinc homeostasis and viability.

    Evidence Cryo-EM; site-directed mutagenesis; intestinal-specific knockout mice; lineage tracing

    PMID:39422023

    Open questions at the time
    • Full-length structure including CTD not resolved
    • Conformational cycle of transport not captured
    • Drug-targetable pockets not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for the CTD's dual interaction with Raf-1 and LTCC β-subunit, whether Zn²⁺/Ca²⁺ vs Zn²⁺/H⁺ exchange selectivity is determined by intrinsic transporter properties or the cellular environment, the identity of the E3 ligase driving zinc-dependent endocytosis, and how ZnT1-ZIP complexes are assembled and regulated at synapses.
  • Full-length cryo-EM structure with CTD not available
  • No reconstituted system comparing H⁺ vs Ca²⁺ coupling
  • E3 ligase for ZnT1 endocytosis unidentified
  • ZIP-ZnT1 complex stoichiometry and regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 8 GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005768 endosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-382551 Transport of small molecules 6 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
CACNBGLUN2AMTF-1RAF-1ZIP1ZIP3

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ZnT-1 (SLC30A1) protein is localized to the basolateral surface of intestinal enterocytes, consistent with a role in transporting dietary zinc from enterocytes to the portal circulation; dietary zinc supplementation upregulates ZnT-1 mRNA and protein in the intestine. Immunofluorescence localization; Western blot; dietary zinc manipulation in intact animals Proceedings of the National Academy of Sciences of the United States of America High 9560190
2000 The transcription factor MTF-1 directly binds to two metal-response elements in the ZnT1 promoter and is essential for both basal and metal (zinc and cadmium)-induced transcriptional regulation of the ZnT1 gene. In vitro DNA-binding assay (EMSA); MTF-1 knockout mouse embryo fibroblasts; RNA synthesis inhibition; dietary zinc manipulation in transgenic mice The Journal of biological chemistry High 10952993
2000 ZnT-1 overexpression in PC12 cells enhances zinc efflux and protects against zinc-induced neurotoxicity, while dominant-negative ZnT-1 reduces zinc efflux and increases vulnerability to zinc-induced death mediated via L-type Ca2+ channels. Stable cell lines overexpressing wild-type or dominant-negative rat ZnT-1; zinc efflux measurements; cell viability assays; pharmacological L-type Ca2+ channel manipulation Brain research High 11119691
2004 ZnT-1 modulates zinc influx rather than efflux by inhibiting zinc permeation through L-type calcium channels (LTCC); co-expression of ZnT-1 with LTCC reduces zinc influx ~3-fold without altering LTCC protein expression. Fluorescent zinc transport measurements in HEK293 and PC-12 cells; co-expression of ZnT-1 with LTCC; immunoblot for LTCC expression Biochemical and biophysical research communications Medium 15451416
2004 Heterologous expression of ZnT-1 in astrocytes slows intracellular zinc accumulation via L-type calcium channels and reduces sensitivity to zinc toxicity; endogenous ZnT-1 expression is induced ~4-fold by sub-lethal zinc preconditioning. Fluorescence cell imaging; heterologous overexpression; immunoblot; immunohistochemistry Glia Medium 15378655
2006 ZnT-1 inhibits L-type calcium channel (LTCC) activity in cardiomyocytes; overexpression decreases and siRNA knockdown increases barium influx through LTCC; rapid pacing increases ZnT-1 expression and inhibits LTCC, and ZnT-1 silencing prevents this pacing-induced LTCC inhibition. ZnT-1 overexpression and siRNA knockdown in cultured cardiomyocytes; co-expression in Xenopus oocytes; rapid pacing of cultured cells and atria in vivo; whole-cell barium current measurements Cell calcium High 17196651
2006 siRNA-mediated silencing of ZnT-1 in cortical neurons increases Ca2+, Zn2+, and Cd2+ influx through L-type calcium channels approximately 4-fold, and increases cadmium-induced neuronal death ~2-fold; ZnT-1 thus modulates cation permeation through LTCC. siRNA silencing; fluorescence imaging of intracellular Ca2+, Zn2+, Cd2+; FM1-43 synaptic release assay; L-type Ca2+ channel pharmacology (nimodipine) Journal of molecular medicine (Berlin, Germany) High 16741752
2008 ZnT1 directly mediates Zn2+ efflux in cortical neurons; shRNA-mediated knockdown of ZnT1 (~40% reduction) causes significant decrease in Zn2+ efflux, demonstrating ZnT1 as a primary route for zinc efflux from neurons. Vector-based shRNA; FluoZin-3 fluorescence microfluorometry; EDTA chelation to measure unopposed efflux Neuroscience letters Medium 19095042
2009 Drosophila ZnT1 (dZnT1), ortholog of human ZnT1, localizes to the basolateral membrane of intestinal enterocytes and is required for dietary zinc absorption; human ZnT1 (but not ZnT7 or ZnT4) rescues zinc-acquisition defects caused by dZnT1 silencing, functionally validating conserved mechanism. Ubiquitous and gut-specific RNAi; dZnT1 overexpression; rescue by human ZnT1; subcellular localization in gut; cell culture zinc efflux assay FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 19325039
2011 ZnT-1 protects cardiomyocytes from ischemia-reperfusion injury through its C-terminal domain interaction with Raf-1 kinase leading to ERK activation; the C-terminal domain alone is sufficient for ERK activation and I/R protection, whereas a truncated ZnT-1 lacking the C-terminal domain fails to activate ERK and does not protect. ZnT-1 overexpression and knockdown in HL-1 cells; C-terminal domain expression constructs; MEK inhibitor (PD98059); LDH release and caspase activation assays; phospho-ERK immunoblot Journal of molecular medicine (Berlin, Germany) High 22193398
2012 ZnT-1 enhances T-type calcium channel (CaV3.1 and CaV3.2) activity and surface expression through activation of Ras-ERK signaling; MEK inhibitor PD-98059 blocks ZnT-1-induced augmentation of CaV3.1 surface expression; co-expression of non-active Raf-1 blocks this effect. Xenopus oocyte electrophysiology; co-expression in CHO cells; biotinylation surface expression assay; TIRF microscopy; MEK inhibitor; dominant-negative Raf-1; ERK phosphorylation immunoblot American journal of physiology. Cell physiology High 22572848
2013 ZnT1, metallothionein (MT), and ZnT4 cooperatively supply zinc in the cytoplasm for full activation of secretory zinc enzyme TNAP in the early secretory pathway; cells deficient in all three (ZnT1−/−MT−/−ZnT4−/−) show reduced TNAP activity that is not rescued by normalizing cytosolic zinc but is rescued by zinc-competent re-expression of ZnT1 or ZnT4. Gene knockout (triple KO cells); TNAP activity reporter assay; zinc supplementation; re-expression of WT vs zinc-transport-incompetent mutants of ZnT1 and ZnT4 PloS one High 24204829
2014 ZnT-1 functions as a Zn2+/H+ exchanger: it mediates sodium-independent, pH-driven, calcium-sensitive zinc efflux from HEK293T cells; substitution of two amino acids in the putative zinc-binding domain abolishes Zn2+ efflux and cellular zinc resistance. Fluorescence imaging (FluoZin-3, Fura-2) in HEK293T cells; site-directed mutagenesis of zinc-binding domain; homology modeling from YiiP crystal structure; pharmacological manipulation of pH and sodium Metallomics : integrated biometal science High 24951051
2016 MTF1 controls ZnT1 and metallothionein expression to buffer cellular zinc homeostasis; MTF1-depleted cells show augmented transcriptomic response to zinc for most genes except ZnT1 and metallothioneins, indicating ZnT1 and MTs together buffer intracellular zinc and limit the zinc-responsive transcriptome. siRNA knockdown of MTF1 in Caco-2 cells; microarray transcriptomics; metallothionein overexpression; SLC30A5 promoter reporter assay Metallomics : integrated biometal science Medium 26824222
2017 ZnT-1 has two structurally independent functions: Zn2+/H+ exchange (mediated by transmembrane helices) and inhibition of L-type calcium channels (mediated by the intracellular C-terminal domain); mutations disabling zinc transport do not prevent LTCC inhibition, and the C-terminal domain alone inhibits LTCC as efficiently as full-length ZnT-1. Site-directed mutagenesis of transmembrane zinc-binding residues; C-terminal domain truncation constructs; barium current measurements in Xenopus oocytes and HEK cells; FluoZin-3 zinc transport assay Metallomics : integrated biometal science High 28091657
2019 ZnT1 accumulates on the plasma membrane under zinc-sufficient conditions and is endocytosed and degraded via both proteasomal and lysosomal pathways under zinc-deficient conditions; ZnT1 is N-glycosylated on Asn299 (extracellular loop between TM domains V and VI), which affects ZnT1 stability (non-glycosylated form is more stable) but not zinc resistance or localization. Immunofluorescence localization; endocytosis and degradation pathway inhibitors; N-glycosylation site mutagenesis (Asn299); zinc resistance assay The Journal of biological chemistry High 31471319
2019 Overexpression of wild-type ZnT1 lowers intracellular zinc levels, while overexpression of predicted deleterious ZnT1 missense mutations fails to reduce intracellular zinc, validating eight mutations as loss-of-function; functional zinc transport assays confirmed the zinc efflux activity of ZnT1. Functional zinc transport assay (cytosolic zinc measurement); overexpression of WT and mutant ZnT1; bioinformatics prediction of deleterious mutations Cell death discovery Medium 31728210
2020 ZnT1 physically associates with the NMDA receptor subunit GluN2A at the postsynapse; disruption of ZnT1-GluN2A association by a cell-permeant peptide strongly reduces NMDAR inhibition by synaptic zinc; postsynaptic intracellular zinc transported by ZnT1 generates a zinc microdomain that inhibits NMDARs. Cell-permeant peptide disruption of ZnT1-GluN2A interaction; electrophysiological recording in mouse dorsal cochlear nucleus synapses; intracellular zinc chelation Science advances High 32937457
2020 SLC30A1 (ZnT1) localizes to both the plasma membrane and intracellular zinc-containing vesicles in LPS-stimulated macrophages; ectopic overexpression of SLC30A1 is sufficient to promote zinc-containing vesicle formation and increase zinc stress in intracellular Escherichia coli, augmenting bacterial clearance. Ectopic SLC30A1 overexpression in THP-1 cells; zinc-stress reporter bacteria; confocal microscopy; CRISPR screen Journal of leukocyte biology Medium 32441444
2021 ZnT1 functions as a Zn2+/Ca2+ exchanger in neurons: ZnT1 knockdown via AAV-shRNA increases rate of cytosolic Zn2+ rise and decreases rate of Zn2+ removal; H+ gradients are not coupled to ZnT1-dependent transport; extracellular Ca2+ is required for and drives ZnT1-dependent Zn2+ efflux, and Ca2+ rises closely parallel Zn2+ removal. AAV-shRNA knockdown; FluoZin-3 Zn2+ imaging; H+ gradient manipulation; Ca2+ removal and supplementation; GCaMP6 Ca2+ imaging in primary mouse cortical neurons Cell calcium High 34871934
2021 Human ZnT1 and a purified variant exhibit Zn2+/H+ antiporter activity when reconstituted in heterologous expression system; the soluble C-terminal domain (hZnT1-CTD) forms a dimer in solution as shown by SAXS; stability of hZnT1-CTD is pH-dependent. Heterologous expression in S. cerevisiae; detergent purification; Zn2+/H+ antiporter activity assay; SAXS analysis of CTD; bacterial expression of CTD Frontiers in chemistry Medium 33996761
2022 Increased intracellular zinc drives MTF-1 activation in cortical neurons, which upregulates ZnT1 expression and increases ZnT1-GluN2A interactions, thereby enhancing tonic zinc inhibition of NMDAR-mediated currents; disruption of GluN2A-ZnT1 interaction abrogates this effect. MTF-1 reporter assay in cortical neurons; cell-permeable peptide disruption of ZnT1-GluN2A; electrophysiological recordings of NMDAR currents Neuroscience letters Medium 36202195
2022 Overexpression of cell-surface ZIPs (ZIP4, ZIP5) increases cellular zinc content and drives compensatory upregulation of plasma-membrane ZnT1 expression without external zinc supplementation; in polarized cells, apical ZIP4 expression facilitates basolateral ZnT1 expression, indicating coordinated vectorial zinc transport. ZIP4/ZIP5 overexpression; ZnT1 protein expression by Western blot; polarized cell (Caco-2) system; zinc content measurement Scientific reports Medium 35513474
2023 Somatic in-frame deletions in SLC30A1 (ZnT1) near the zinc-binding site (His43, Asp47 in TM domain II) cause pathological Na+ influx, membrane depolarization, voltage-gated Ca2+ channel opening, increased cytosolic Ca2+, and stimulation of CYP11B2 mRNA and aldosterone production in adrenal cells. Next-generation sequencing of APAs/APNs; doxycycline-inducible expression of SLC30A1Δ51_57del in adrenal cell system; Na+ current measurement; Ca2+ imaging; CYP11B2 mRNA quantification; aldosterone measurement Nature genetics High 37709865
2023 ZnT1 regulates endosomal zinc levels to control endocytosis of TLR4 and PD-L1 in macrophages; myeloid-specific ZnT1 knockout increases TLR4 and PD-L1 surface expression, chronic inflammation, and liver tumor burden; zinc supplementation reduces PD-L1 surface expression in a ZNT1-dependent manner. Myeloid-specific (Lyz2-Cre) Slc30a1 conditional knockout mice; flow cytometry for surface TLR4 and PD-L1; tumor model; zinc supplementation Hepatology (Baltimore, Md.) High 37816045
2023 ZnT1 interacts with both Raf-1 kinase and the VGCC β-subunit; the β-subunit inhibits ZnT1-induced Ras-ERK activation and consequently reduces ZnT1-mediated augmentation of T-type calcium channel (TTCC) surface expression, revealing a ZnT1-mediated crosstalk between LTCC and TTCC. Co-expression in Xenopus oocytes; binding/interaction assays; ERK phosphorylation; surface expression assay; endothelin-1 as control activator Metallomics : integrated biometal science Medium 37193665
2024 Intestinal Slc30a1 (ZnT1) is essential for systemic zinc homeostasis and survival; lineage tracing shows ZnT1 localizes to the basolateral membrane of intestinal epithelial cells; cryo-EM structure combined with site-specific mutagenesis identifies His43 as a critical residue for zinc selectivity, and reveals a unique zinc transport mechanism within the SLC30A family. Intestinal-specific knockout mice; lineage tracing; cryo-EM structural determination; site-specific mutagenesis; zinc transport assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 39422023
2024 Myeloid-specific Slc30a1 knockout macrophages show defective intracellular killing of Salmonella correlated with reduced NF-κB activation and reduced nitric oxide production; Slc30a1-deficient macrophages accumulate intracellular zinc, confirming its zinc export function is required for NO-mediated antibacterial activity. Lyz2-Cre conditional knockout mice; Salmonella infection model; NF-κB activation assay; NO production measurement; intracellular zinc imaging eLife High 39475776
2021 Slc30a1a/b (ZnT1 orthologs) deficiency in zebrafish causes zinc accumulation in neural crest (NC) cells, increases NC stemness markers, and impairs pharyngeal arch (PA) differentiation; snai2 and jag1b are downstream targets; the double zinc-finger domain of Snai2 is a zinc-responsive element regulating jag1b; knockdown of snai2 or jag1b rescues PA development. Slc30a1 mutant zebrafish; SMART-seq transcriptomics; in situ hybridization; snai2 and jag1b knockdown rescue experiments; zinc-finger domain functional analysis MedComm Medium 34977877
2026 ZIP3 physically interacts with ZnT1 in dorsal cochlear nucleus neurons and ZIP1 interacts with ZnT1 in hippocampal CA3 cells; ZIP-ZnT1 complexes form local Zn2+ microdomains that enhance ZnT1-dependent Zn2+ efflux; co-expression of ZnT1 with ZIP3 or ZIP1 increases Zn2+ efflux rates compared to ZnT1 alone. Co-immunoprecipitation/interaction assays; ZIP3 knockout; FluoZin-3 Zn2+ imaging; co-expression in SH-SY5Y cells; dorsal cochlear nucleus and hippocampus neurophysiology Cellular and molecular life sciences : CMLS Medium 41779239

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. The Journal of biological chemistry 325 10952993
1998 Regulation of the zinc transporter ZnT-1 by dietary zinc. Proceedings of the National Academy of Sciences of the United States of America 239 9560190
2003 Induction of the ZRC1 metal tolerance gene in zinc-limited yeast confers resistance to zinc shock. The Journal of biological chemistry 137 12556516
1997 Expression of zinc transporter gene, ZnT-1, is induced after transient forebrain ischemia in the gerbil. The Journal of neuroscience : the official journal of the Society for Neuroscience 110 9254680
2007 Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9. Journal of leukocyte biology 93 17971500
2019 Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels. The Journal of biological chemistry 90 31471319
2000 L-type Ca(2+) channel-mediated Zn(2+) toxicity and modulation by ZnT-1 in PC12 cells. Brain research 86 11119691
2004 ZnT-1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc. Glia 84 15378655
2002 Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain. The Journal of comparative neurology 81 11984815
2016 Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc. Metallomics : integrated biometal science 76 26824222
2009 Dietary zinc absorption is mediated by ZnT1 in Drosophila melanogaster. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 76 19325039
2006 Immunohistochemical analysis of ZnT1, 4, 5, 6, and 7 in the mouse gastrointestinal tract. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 76 17101726
2005 Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease. Neurotoxicity research 70 16179263
2014 ZnT-1 extrudes zinc from mammalian cells functioning as a Zn(2+)/H(+) exchanger. Metallomics : integrated biometal science 68 24951051
2008 Zinc transporters ZnT1 (Slc30a1), Zip8 (Slc39a8), and Zip10 (Slc39a10) in mouse red blood cells are differentially regulated during erythroid development and by dietary zinc deficiency. The Journal of nutrition 65 18936201
2005 Zinc deficiency is associated with increased brain zinc import and LIV-1 expression and decreased ZnT-1 expression in neonatal rats. The Journal of nutrition 62 15867272
2006 Silencing of ZnT-1 expression enhances heavy metal influx and toxicity. Journal of molecular medicine (Berlin, Germany) 60 16741752
2004 A role for ZnT-1 in regulating cellular cation influx. Biochemical and biophysical research communications 60 15451416
2010 Increased level of exogenous zinc induces cytotoxicity and up-regulates the expression of the ZnT-1 zinc transporter gene in pancreatic cancer cells. The Journal of nutritional biochemistry 58 20392624
2020 Synaptic zinc inhibition of NMDA receptors depends on the association of GluN2A with the zinc transporter ZnT1. Science advances 53 32937457
2001 The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae. Biochemical and biophysical research communications 48 11263974
2023 Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism. Nature genetics 43 37709865
2016 Expression of the ZNT1 Zinc Transporter from the Metal Hyperaccumulator Noccaea caerulescens Confers Enhanced Zinc and Cadmium Tolerance and Accumulation to Arabidopsis thaliana. PloS one 43 26930473
2003 Zinc accumulation in N-methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered expression of ZnT-1 and metallothionein. Experimental biology and medicine (Maywood, N.J.) 42 12773700
2008 Silencing of ZnT1 reduces Zn2+ efflux in cultured cortical neurons. Neuroscience letters 41 19095042
2006 Crosstalk between L-type calcium channels and ZnT-1, a new player in rate-dependent cardiac electrical remodeling. Cell calcium 37 17196651
2000 Expression of ZRC1 coding for suppressor of zinc toxicity is induced by zinc-starvation stress in Zap1-dependent fashion in Saccharomyces cerevisiae. Biochemical and biophysical research communications 36 11027563
2010 Characterization of the ER-located zinc transporter ZnT1 and identification of a vesicular zinc storage compartment in Hebeloma cylindrosporum. Fungal genetics and biology : FG & B 33 21134481
2019 Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer. Cell death discovery 31 31728210
2013 Cooperative functions of ZnT1, metallothionein and ZnT4 in the cytoplasm are required for full activation of TNAP in the early secretory pathway. PloS one 31 24204829
2012 ZnT-1 enhances the activity and surface expression of T-type calcium channels through activation of Ras-ERK signaling. American journal of physiology. Cell physiology 31 22572848
2011 ZnT-1 protects HL-1 cells from simulated ischemia-reperfusion through activation of Ras-ERK signaling. Journal of molecular medicine (Berlin, Germany) 31 22193398
2005 Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 30 15995149
2008 ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats. Toxicology letters 29 19059322
2002 Postnatal regulation of ZnT-1 expression in the mouse brain. Brain research. Developmental brain research 29 12220707
2018 MiR-411 suppresses the development of bladder cancer by regulating ZnT1. OncoTargets and therapy 26 30584327
2009 Regulation of metallothioneins and ZnT-1 transporter expression in human hepatoma cells HepG2 exposed to zinc and cadmium. Toxicology in vitro : an international journal published in association with BIBRA 25 19900532
2008 A single amino acid change in the yeast vacuolar metal transporters ZRC1 and COT1 alters their substrate specificity. The Journal of biological chemistry 25 18930916
2022 Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs. Scientific reports 24 35513474
2021 ZnT1 is a neuronal Zn2+/Ca2+ exchanger. Cell calcium 24 34871934
2009 Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity. The Biochemical journal 22 19538181
2023 ZNT1 and Zn 2+ control TLR4 and PD-L1 endocytosis in macrophages to improve chemotherapy efficacy against liver tumor. Hepatology (Baltimore, Md.) 21 37816045
2020 Frontline Science: LPS-inducible SLC30A1 drives human macrophage-mediated zinc toxicity against intracellular Escherichia coli. Journal of leukocyte biology 20 32441444
2017 Zinc transport and the inhibition of the L-type calcium channel are two separable functions of ZnT-1. Metallomics : integrated biometal science 20 28091657
2007 Correlation between atrial ZnT-1 expression and atrial fibrillation in humans: a pilot study. Journal of cardiovascular electrophysiology 20 17971132
2019 The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection. Scientific reports 19 31320712
2003 Different induction of metallothioneins and Hsp70 and presence of the membrane transporter ZnT-1 in HepG2 cells exposed to copper and zinc. Toxicology in vitro : an international journal published in association with BIBRA 19 14599444
2017 Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters ZIP14 and ZNT1 in Obesity and Polycystic Ovary Syndrome. Frontiers in endocrinology 18 28303117
2007 Cortisol stimulates the zinc signaling pathway and expression of metallothioneins and ZnT1 in rainbow trout gill epithelial cells. American journal of physiology. Regulatory, integrative and comparative physiology 18 18077514
2007 Expression of ZnT-1 (Slc30a1) and MT-1 (Mt1) in the conceptus of cadmium treated mice. Reproductive toxicology (Elmsford, N.Y.) 15 17669619
2024 The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 39422023
2018 Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans. Journal of microbiology (Seoul, Korea) 14 29299844
2021 Heterologous Expression and Biochemical Characterization of the Human Zinc Transporter 1 (ZnT1) and Its Soluble C-Terminal Domain. Frontiers in chemistry 13 33996761
2010 The correlation among the dynamic change of Zn2+, ZnT-1, and brain-derived neurotrophic factor after acute spinal cord injury in rats. Biological trace element research 13 20838921
2021 Enhancement of Zn tolerance and accumulation in plants mediated by the expression of Saccharomyces cerevisiae vacuolar transporter ZRC1. Planta 12 33956221
2020 The Roles of ZnT1 and ZnT4 in Glucose-Stimulated Zinc Secretion in Prostate Epithelial Cells. Molecular imaging and biology 12 33140261
2006 Cadmium and zinc induction of ZnT-1 mRNA in an established carp cell line. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 12 16627006
2022 The correlation and role analysis of SLC30A1 and SLC30A10 in cervical carcinoma. Journal of Cancer 10 35154468
2022 Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A. Neuroscience letters 10 36202195
2011 The effects of transformation and ZnT-1 silencing on zinc homeostasis in cultured cells. The Journal of nutritional biochemistry 10 21775119
2020 Drosophila ZnT1 is essential in the intestine for dietary zinc absorption. Biochemical and biophysical research communications 9 33012507
2024 The zinc transporter Slc30a1 (ZnT1) in macrophages plays a protective role against attenuated Salmonella. eLife 8 39475776
2019 MiRNA-8073 targets ZnT1 to inhibit malignant progression of ovarian cancer. European review for medical and pharmacological sciences 8 31364107
2010 The involvement of ZnT-1, a new modulator of cardiac L-type calcium channels, in [corrected] atrial tachycardia remodeling. [corrected]. Annals of the New York Academy of Sciences 8 20201890
2021 Overexpression of ZNT1 and NRAMP4 from the Ni Hyperaccumulator Noccaea caerulescens Population Monte Prinzera in Arabidopsis thaliana Perturbs Fe, Mn, and Ni Accumulation. International journal of molecular sciences 7 34769323
2021 Metal transporter Slc30a1 controls pharyngeal neural crest differentiation via the zinc-Snai2-Jag1 cascade. MedComm 6 34977877
2016 ZNT-1 Expression Reduction Enhances Free Zinc Accumulation in Astrocytes After Ischemic Stroke. Acta neurochirurgica. Supplement 6 26463958
2023 ZnT1 induces a crosstalk between T-type and L-type calcium channels through interactions with Raf-1 kinase and the calcium channel β2 subunit. Metallomics : integrated biometal science 5 37193665
2021 HPV infection upregulates the expression of ZNT-1 in condyloma acuminatum. European journal of histochemistry : EJH 3 33908744
2011 Rapid homeostatic response of H4IIE cells to diethylenetriaminepentaacetic acid is not due to changes in the amount or localization of ZnT-1 protein. Nutrition research (New York, N.Y.) 3 21636019
2024 Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue. Biological trace element research 2 38319549
2007 Age-dependent oxidation and aggregation of ZnT-1: a role for metal catalyzed oxidation? Experimental gerontology 2 17997256
2025 Modulation of ZnT-1 by Let7a unveils a therapeutic potential in amyotrophic lateral sclerosis. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 1 40113485
2022 Zinc transporter Slc30a1 regulates melanocyte development by interacting with mt2 in zebrafish. European journal of cell biology 1 36063588
2026 Piezo1 Regulates ZnT1-Mediated Zinc Homeostasis in Ulcerative Colitis. Inflammation 0 41586934
2026 ZIP-ZnT1 complexes mediate a local Zn2+-cycle regulating neuronal Zn²⁺ transport. Cellular and molecular life sciences : CMLS 0 41779239
2026 SLC30A1, SLC30A5, and SLC30A9 transporters play crucial role in ligand-independent activation of ESR1 signalling in breast cancer cells via modulation of AKT activity by zinc. Metallomics : integrated biometal science 0 41790496
2026 The role of zinc transporter 1 (ZnT1) in health and disease: From molecular mechanisms to therapeutic opportunities. European journal of medicinal chemistry 0 41833275
2025 Ginsenoside Ro alleviated cuproptosis induced by high oxalate via inhibiting zinc transporter ZnT1 in renal tubular epithelial cells. Journal of ginseng research 0 41550586
2024 CDF family of zinc transporters ZRC-1, MSC-2, and ZRG-17 are involved in survival at high zinc conditions, vegetative development, and cellulase utilization in Neurospora crassa. Journal of biosciences 0 38186003
2024 ZNT1 Regulates the Proliferation, Migration and Invasion of HaCaT Cells Infected with HPV Through the PI3K/Akt Pathway. Indian journal of dermatology 0 38841228