Affinage

SLC39A14

Metal cation symporter ZIP14 · UniProt Q15043

Length
492 aa
Mass
54.2 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC39A14/ZIP14 is a broad-scope divalent metal-ion transporter that mediates cellular uptake of Fe2+, Zn2+, Mn2+, and Cd2+ through an electroneutral metal/bicarbonate symport mechanism, operating at the plasma membrane and within endosomes to govern systemic metal homeostasis (PMID:18270315, PMID:21653899, PMID:23090441). It transports ferrous (but not ferric) iron and is responsible for non-transferrin-bound iron uptake as well as assimilation of transferrin-derived iron at endosomal pH, with prion protein serving as a ferrireductase partner that supplies Fe2+ from Fe3+ (PMID:16950869, PMID:20682781, PMID:25862412). In the liver, ZIP14 drives NTBI uptake and delivers zinc that inhibits PTP1B to enhance c-Met signaling and hepatocyte proliferation, supports adaptation to ER stress, and traffics through endosomes to supply zinc-dependent insulin-degrading enzyme and cathepsin D, thereby regulating insulin receptor turnover and glucose homeostasis (PMID:22374166, PMID:27703010, PMID:28673968). ZIP14 expression is induced by inflammatory signals — IL-6 in liver, IL-1β via iNOS-derived nitric oxide and AP-1, and ATF4/ATF6α during ER stress — and is post-translationally controlled by iron through an N102-glycosylation-dependent membrane-extraction and proteasomal degradation pathway, by Mn through lysosomal degradation, by p53-mediated ubiquitination, and by HFE-mediated destabilization (PMID:15863613, PMID:19179618, PMID:24927598, PMID:26028554, PMID:29292794, PMID:28673968, PMID:31541377, PMID:18524764). In the intestine ZIP14 localizes basolaterally to restrict net manganese absorption and to supply labile zinc that sustains HDAC activity, tight-junction integrity, and MHCII/CIITA expression, while in skeletal muscle ZIP14-mediated zinc accumulation represses MyoD and Mef2c to block myogenesis and drive cancer cachexia (PMID:31028174, PMID:36537699, PMID:39793074, PMID:29875463). Loss of ZIP14 across intestinal, hepatic, and non-hepatic tissues causes systemic manganese overload with brain accumulation and motor deficits, and a dominant gain-of-function mutation trapping ZIP14 intracellularly causes a hyperostosis bone phenotype through cAMP-CREB/NFAT activation (PMID:28751976, PMID:31028174, PMID:35742937, PMID:29621230).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 2005 High

    Established ZIP14 as a functional plasma-membrane zinc influx transporter and linked it to inflammation-driven hypozincemia, defining a first physiological context.

    Evidence Overexpression zinc-transport assays plus IL-6 knockout mouse and hepatocyte transfection

    PMID:15642354 PMID:15863613

    Open questions at the time
    • Did not establish substrate breadth beyond zinc
    • Transcription factor mediating IL-6 induction not yet defined
  2. 2006 High

    Showed ZIP14 transports non-transferrin-bound iron as Fe2+ in addition to zinc, expanding it from a zinc transporter to a multi-metal transporter.

    Evidence Radioisotope uptake in HEK293H and Sf9 overexpression and hepatocyte siRNA knockdown with ferrous chelator

    PMID:16950869

    Open questions at the time
    • Did not determine kinetics or full metal selectivity
    • Did not address transferrin-bound iron pathway
  3. 2008 High

    Defined the transport mechanism as metal/bicarbonate symport and characterized two splice isoforms (ZIP14A/B) with distinct Cd2+/Mn2+ affinities, establishing the biochemical basis of substrate handling.

    Evidence Kinetic uptake assays of two isoforms in fibroblasts and polarized MDCK cells with HCO3- dependence

    PMID:18270315

    Open questions at the time
    • Physiological roles of isoform differences not addressed
    • Electroneutrality not yet proven electrophysiologically
  4. 2008 High

    Identified HFE as a post-translational destabilizer of ZIP14 that reduces both TBI and NTBI uptake, connecting ZIP14 to hereditary hemochromatosis regulation.

    Evidence HFE overexpression plus ZIP14 siRNA epistasis and protein half-life assays in HepG2/HeLa cells

    PMID:18524764

    Open questions at the time
    • Molecular mechanism of HFE-mediated destabilization not resolved
    • Direct HFE-ZIP14 interaction not demonstrated
  5. 2009 High

    Defined a second inflammatory induction route, showing IL-1β induces ZIP14 via iNOS-derived NO acting through AP-1 at the promoter.

    Evidence NO donor and iNOS-/- hepatocytes with ChIP for AP-1 and RNA Pol II

    PMID:19179618

    Open questions at the time
    • Did not link induction to downstream metal-dependent function
    • AP-1 subunit identity not specified
  6. 2010 High

    Showed ZIP14 assimilates transferrin-derived iron from endosomes at acidic pH, revealing an endosomal arm of its iron-handling role beyond plasma-membrane NTBI uptake.

    Evidence FLAG knock-in HepG2 cells, confocal co-localization with transferrin endosomes, siRNA, pH-dependent transport

    PMID:20682781

    Open questions at the time
    • Endosomal recruitment mechanism not defined
    • Quantitative contribution versus DMT1 not resolved
  7. 2010 Medium

    Connected ZIP14 isoform splicing to Wnt/β-catenin signaling via SRSF1/SRPK1 in colorectal cancer, linking transporter isoform choice to an oncogenic pathway.

    Evidence β-catenin and TCF perturbation plus SRSF1/SRPK1 knockdown and exon arrays in colon cancer lines

    PMID:20938052

    Open questions at the time
    • SRSF1 binding partly in silico predicted
    • Functional metal-transport consequence of isoform switch not measured
  8. 2011 High

    Provided rigorous reconstituted kinetics establishing ZIP14 selectivity (Fe2+, Zn2+, Cd2+, Mn2+ but not Cu) and ion dependencies, giving a definitive biophysical substrate map.

    Evidence Xenopus oocyte heterologous expression with multi-isotope kinetic and ion-dependence analysis

    PMID:21653899

    Open questions at the time
    • Structural basis of selectivity unknown
    • Differing Fe2+ vs Zn2+ inhibition profiles mechanistically unexplained
  9. 2011 Medium

    Linked ZIP14 to GPCR cAMP-CREB signaling via suppression of phosphodiesterase activity, implicating it in growth and gluconeogenesis phenotypes.

    Evidence Slc39a14 KO mice with cAMP, PDE activity, and CREB phosphorylation readouts

    PMID:21445361

    Open questions at the time
    • Mechanistic link from zinc transport to PDE inhibition inferred not shown
    • Which PDE isoform involved unresolved
  10. 2012 High

    Established hepatic ZIP14 as a driver of regeneration by importing zinc to inhibit PTP1B and enhance c-Met signaling, defining a signaling-via-metal mechanism.

    Evidence Partial hepatectomy in Zip14 KO mice plus hepatocyte overexpression with PTP1B activity and c-Met phosphorylation

    PMID:22374166

    Open questions at the time
    • Direct zinc-PTP1B inhibition in vivo not quantified
    • Endosomal versus cytosolic zinc pool not distinguished
  11. 2012 Medium

    Mapped intestinal and renal localization, showing basolateral enterocyte and apical proximal-tubule roles in metal transport, and demonstrated endosomal zinc trafficking required for barrier integrity.

    Evidence Fractionation, FluoZin imaging, permeability and occludin assays in Zip14 KO intestine; siRNA in proximal tubule Transwell

    PMID:22534978 PMID:25428902

    Open questions at the time
    • Overlap with ZIP8 not fully resolved
    • Mechanism of occludin phosphorylation regulation not defined
  12. 2012 High

    Confirmed electroneutral divalent-cation/bicarbonate symport electrophysiologically and showed isoform-specific inhibition patterns, finalizing the transport mechanism.

    Evidence Xenopus oocyte electrogenicity studies with potassium gradient and competitive inhibition

    PMID:23090441

    Open questions at the time
    • Stoichiometry of metal:bicarbonate not precisely fixed
    • Structural transporter model absent
  13. 2012 Medium

    Showed ZIP14 buffers macrophage inflammatory responses through LPS-induced zinc uptake, broadening its role to innate immunity.

    Evidence LPS treatment and siRNA in primary human macrophages with cytokine readouts and pathway inhibitors

    PMID:23052185

    Open questions at the time
    • Direct transcription factor at promoter not pinned
    • Single lab
  14. 2013 Medium

    Demonstrated iron-status-dependent post-translational upregulation of ZIP14 protein (opposite to DMT1), establishing iron as a regulator of transporter abundance.

    Evidence Immunofluorescence and immunoblotting versus qRT-PCR across iron-status rat and hypotransferrinemic models

    PMID:23349308

    Open questions at the time
    • Degradation mechanism not yet defined here
    • mRNA/protein discordance only correlative
  15. 2014 High

    Defined the iron-sensitive degradation pathway: endocytosis, N102-glycosylation-dependent membrane extraction, deglycosylation, and ERAD-independent proteasomal degradation, explaining iron-regulated ZIP14 stability.

    Evidence Inhibitor panels, N102 glycosylation mutants, pulse-chase and endocytosis assays

    PMID:24927598

    Open questions at the time
    • Ubiquitin ligase mediating degradation not identified
    • How iron blocks membrane extraction mechanistically unknown
  16. 2014 Medium

    Extended IL-6 induction of ZIP14 to neuronal cells, where it raises Mn uptake while ZnT10 downregulation limits efflux, implicating ZIP14 in neuronal Mn accumulation.

    Evidence siRNA and IL-6 treatment with Mn uptake assays in SH-SY5Y cells

    PMID:24576911

    Open questions at the time
    • In vivo neuronal relevance not tested
    • Transcription factor for neuronal IL-6 induction unspecified
  17. 2015 High

    Demonstrated in vivo that ZIP14 is the major route of hepatic/pancreatic NTBI loading and is required for iron deposition in hemochromatosis models, establishing it as a therapeutic node in iron overload.

    Evidence Slc39a14 KO crossed with Hfe-/- and Hfe2-/- mice with in vivo NTBI uptake and tissue iron histology

    PMID:26028554

    Open questions at the time
    • Did not address extrahepatic iron handling
    • Contribution to systemic iron balance versus other transporters not quantified
  18. 2015 Medium

    Identified prion protein as a ferrireductase partner supplying Fe2+ to ZIP14, providing a mechanism for ferric iron utilization.

    Evidence PrPC KO mice and HepG2 coexpression with ferric versus ferrous uptake

    PMID:25862412

    Open questions at the time
    • Ferrireductase activity not proven by reconstitution
    • Physical PrPC-ZIP14 interaction not shown
  19. 2016 High

    Revealed ZIP14-mediated endosomal zinc delivery controls insulin receptor degradation via IDE and cathepsin D, mechanistically connecting ZIP14 trafficking to glucose homeostasis.

    Evidence Zip14 KO hepatocytes with endosome fractionation, IDE/cathepsin D activity, insulin receptor signaling and metabolic assays

    PMID:27703010

    Open questions at the time
    • Trigger for plasma-membrane-to-endosome translocation unresolved
    • Direct zinc loading of IDE not demonstrated structurally
  20. 2016 Medium

    Showed ZIP14 contributes ~50% of β-cell NTBI uptake, extending its iron role to islet cells.

    Evidence siRNA and overexpression with NTBI uptake in βlox5 cells and primary human islets

    PMID:27903581

    Open questions at the time
    • Functional consequence for β-cell iron physiology not addressed
    • Single lab
  21. 2016 High

    Identified ZIP14 as a driver of cancer cachexia, where cytokine-induced zinc accumulation represses MyoD/Mef2c to block myogenesis, providing a metal-dependent atrophy mechanism.

    Evidence Germline and muscle-specific Zip14 KO across multiple metastatic cancer models with cytokine treatment and myogenic marker analysis

    PMID:29875463

    Open questions at the time
    • How zinc represses MyoD/Mef2c mechanistically not fully defined
    • Therapeutic window in humans not addressed
  22. 2017 High

    Established ZIP14 as required for hepatic ER-stress adaptation, with ATF4/ATF6α driving its transcription and ZIP14-zinc suppressing PTP1B to limit apoptosis and steatosis.

    Evidence ER-stress Zip14 KO mice with ATF4/ATF6α overexpression, PTP1B activity, apoptosis and steatosis readouts

    PMID:28673968

    Open questions at the time
    • Direct ATF binding sites on Zip14 promoter not mapped here
    • Relationship to inflammatory induction routes unresolved
  23. 2017 Medium

    Identified p53 as a binding partner promoting ZIP14 ubiquitination and degradation, adding a tumor-suppressor-linked layer of post-translational control over iron uptake.

    Evidence Co-precipitation, ubiquitination assay, p53 perturbation with NTBI uptake

    PMID:29292794

    Open questions at the time
    • E3 ligase recruited by p53 not identified
    • Direct versus indirect interaction not fully resolved
  24. 2017 High

    Distinguished organ-specific Mn-clearance roles, showing global but not hepatocyte-specific Zip14 loss causes brain Mn accumulation, establishing that non-hepatic ZIP14 prevents systemic Mn overload and underlies the hypermanganesemia-dystonia disease.

    Evidence Global and hepatocyte-specific Slc39a14 KO mice with ICP-MS, motor assays, chelation rescue

    PMID:28751976

    Open questions at the time
    • Identity of the critical non-hepatic tissue not yet pinpointed here
    • Mechanism of Mn excretion downstream of uptake not defined
  25. 2018 High

    Defined a dominant gain-of-function mutation (L441R) trapping ZIP14 intracellularly to cause zinc accumulation and cAMP-CREB/NFAT hyperactivation, producing a hyperostosis bone phenotype and revealing trafficking-dependent signaling control.

    Evidence Patient exome sequencing and osteoblast-specific L438R knock-in mice with localization, zinc, and signaling assays

    PMID:29621230

    Open questions at the time
    • How intracellular zinc activates CREB/NFAT mechanistically unresolved
    • Relationship to loss-of-function Mn phenotype not integrated
  26. 2018 Medium

    Showed ZIP14 mediates bidirectional Mn flux across the blood-brain barrier with pH/bicarbonate/LPS dependence, situating it in CNS metal entry.

    Evidence siRNA, surface biotinylation, and directional 54Mn uptake in brain microvascular endothelial cells

    PMID:31699897

    Open questions at the time
    • Net directional contribution in vivo not established
    • Overlap with ZIP8 not resolved
  27. 2019 High

    Identified intestinal basolateral ZIP14 as the gatekeeper restricting net Mn absorption, with loss causing hepatic and brain Mn accumulation.

    Evidence CRISPR ZIP14-deficient CaCo-2 Transwell directional transport and intestine-specific Zip14 KO mice with ICP-MS

    PMID:31028174

    Open questions at the time
    • Coordination with hepatic clearance not yet tested
    • Mn re-secretion route into lumen not fully defined
  28. 2019 Medium

    Showed Mn-induced lysosomal degradation of ZIP14 provides cytoprotective feedback limiting Mn uptake, complementing the iron-sensitive proteasomal route.

    Evidence Bafilomycin inhibition, LAMP1 co-localization and Mn uptake in polarized HepaRG cells

    PMID:31541377

    Open questions at the time
    • Trigger sensing Mn for lysosomal targeting unknown
    • Single lab
  29. 2019 Medium

    Demonstrated SPCA1-controlled cytoplasmic Ca2+ regulates ZIP14 plasma-membrane occupancy and Mn uptake, adding a calcium-dependent trafficking control.

    Evidence Surface biotinylation, SPCA1 RNAi, Ca2+ chelation and 54Mn uptake in brain endothelial cells

    PMID:35787370

    Open questions at the time
    • Molecular link from Ca2+ to ZIP14 trafficking unknown
    • In vivo relevance untested
  30. 2020 Medium

    Showed ZIP14 has a basal homeostatic role in skeletal muscle, with deletion causing wasting via Mef2c/p38/NF-κB dysregulation and inflammatory zinc uptake driving atrophy gene signatures.

    Evidence Zip14 KO mice with LPS challenge, microarray, ChIP at Mef2c promoter, and atrophy marker analysis

    PMID:32132660

    Open questions at the time
    • Reconciliation of basal protective role with cachexia-driving role incomplete
    • miRNA mechanism downstream not defined
  31. 2022 High

    Linked intestinal ZIP14-supplied zinc to HDAC3 activity and epigenetic control of barrier and cytokine genes, defining a zinc-to-chromatin axis in gut homeostasis.

    Evidence Enterocyte-specific Zip14 KO with RNA-seq, ChIP for NF-κB/STAT3/CDX2, HDAC activity, and zinc-rescue organoids

    PMID:36537699

    Open questions at the time
    • How labile zinc tunes HDAC3 activity mechanistically unresolved
    • Causal chain to disease phenotype not fully mapped
  32. 2022 Medium

    Showed intestinal and hepatic ZIP14 cooperate, with double deletion causing far greater Mn overload than single-tissue loss, defining a multi-organ clearance system.

    Evidence Intestine-, liver-, and double-tissue Slc39a14 KO mice with ICP-MS

    PMID:35742937

    Open questions at the time
    • Quantitative partition between organs not resolved
    • Single lab
  33. 2023 High

    Revealed a non-canonical ER-localized ZIP14 in pancreatic β cells acting as a negative regulator of glucose-stimulated insulin secretion, distinguishing it from plasma-membrane ZIP14 roles.

    Evidence β cell-specific Zip14 KO with ER co-localization, insulin secretion in vivo/ex vivo/MIN6, and metabolic phenotyping

    PMID:38019082

    Open questions at the time
    • Mechanism by which ER zinc trafficking restrains secretion unresolved
    • Relationship to hepatic glucose roles not integrated
  34. 2024 High

    Connected intestinal ZIP14-supplied labile zinc to chromatin accessibility at MHCII loci and CIITA expression, extending the zinc-chromatin axis to mucosal immune gene regulation.

    Evidence Enterocyte-specific Zip14 KO with ATAC-seq, CIITA ChIP, zinc measurement and organoid zinc rescue

    PMID:39793074

    Open questions at the time
    • Direct zinc-dependent factor controlling chromatin not identified
    • Functional immune consequence in vivo not fully tested
  35. 2024 Medium

    Defined a feedforward transcriptional loop in which zinc increases ZIP14 via MTF1 binding and HDAC4 release at the promoter in liver fibrosis.

    Evidence CCl4 fibrosis model with ZnCl2 treatment and ChIP for MTF1/HDAC4 at the ZIP14 promoter

    PMID:38221603

    Open questions at the time
    • Causal contribution to fibrosis outcome not established
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZIP14 trafficking between plasma membrane, endosomes, and ER is selected in a tissue-specific manner, and the structural basis of its metal selectivity, remain unresolved.
  • No structural model of the transporter exists in the corpus
  • Signals directing ER versus plasma-membrane localization across cell types unknown
  • The E3 ligases and sensors coupling iron/Mn levels to degradation are not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-382551 Transport of small molecules 6 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3
Partners
HFEPRPCPTP1BTP53

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ZIP14 (SLC39A14) is a plasma membrane-localized glycoprotein that functions as a zinc influx transporter in a temperature-dependent manner. The LZT metalloprotease motif (HEXPHEXGD) in transmembrane domain V is relevant to zinc transport, though ZIP14 lacks the initial histidine yet retains transport activity. Overexpression in cells with functional zinc transport assay (temperature-dependence), glycosylation analysis FEBS letters Medium 15642354
2005 IL-6 upregulates ZIP14 expression in liver, and this ZIP14 induction drives hepatic zinc import and contributes to hypozincemia during acute-phase inflammatory response. ZIP14 localizes to the plasma membrane of hepatocytes and increases zinc uptake when transfected into HEK cells. IL-6 knockout mouse model (turpentine inflammation, LPS), immunohistochemistry, transfection with 65Zn accumulation and fluorescent Zn probe, metallothionein mRNA induction Proceedings of the National Academy of Sciences of the United States of America High 15863613
2006 ZIP14 mediates cellular uptake of non-transferrin-bound iron (NTBI) as Fe2+ (inhibited by bathophenanthroline sulfonate, a cell-impermeant ferrous chelator) and zinc; overexpression in HEK 293H and Sf9 cells increases 65Zn and 59Fe uptake; siRNA knockdown in AML12 hepatocytes reduces both iron and zinc uptake. Overexpression in HEK 293H and Sf9 cells with radioisotope uptake (65Zn, 59Fe); siRNA knockdown in hepatocytes; ferrous chelator inhibition Proceedings of the National Academy of Sciences of the United States of America High 16950869
2008 ZIP14A and ZIP14B (arising from alternative splicing of exons 4A/4B) function as metal/bicarbonate symporters transporting Cd2+, Mn2+, and Zn2+. ZIP14B has higher affinity than ZIP14A for Cd2+ (Km=0.14 vs 1.1 µM) and Mn2+ (Km=4.4 vs 18.2 µM). Uptake is dependent on extracellular HCO3-. ZIP14 is glycosylated and localizes to the apical surface of polarized MDCK cells. Stable retroviral-infected mouse fetal fibroblast cultures; transient transfection in MDCK polarized epithelial cells; kinetic uptake assays with Cd, Mn, Zn; HCO3- dependence; glycosylation analysis; subcellular localization Molecular pharmacology High 18270315
2008 HFE (hereditary hemochromatosis protein) decreases ZIP14 protein levels post-translationally (without changing ZIP14 mRNA), shortening its half-life, thereby reducing both transferrin-bound and non-transferrin-bound iron uptake in HepG2 cells. ZIP14 knockdown abolishes HFE's effect on NTBI uptake. HFE overexpression in HepG2 and HeLa cells; siRNA knockdown of ZIP14; protein half-life/turnover assays; NTBI uptake assays The Journal of biological chemistry High 18524764
2009 IL-1β upregulates ZIP14 expression and zinc transport in hepatocytes via inducible nitric oxide synthase (iNOS)-generated nitric oxide (NO). The NO donor SNAP increases Zip14 mRNA and transcriptional activity; ChIP showed AP-1 and RNA polymerase II association with Zip14 promoter after NO exposure; induction was absent in iNOS-/- hepatocytes. Primary hepatocyte culture with NO donor (SNAP); IL-1β treatment of WT and iNOS-/- hepatocytes; ChIP for AP-1 and RNA Pol II; zinc fluorophore transport assay; RT-PCR American journal of physiology. Gastrointestinal and liver physiology High 19179618
2010 ZIP14 mediates cellular assimilation of iron from transferrin (transferrin-bound iron, TBI) via endosomal localization. ZIP14 is detected at the plasma membrane and in endosomes containing internalized transferrin in HepG2 cells; siRNA knockdown reduces iron assimilation from transferrin by 50% without affecting transferrin uptake; ZIP14 can transport iron at pH 6.5 (the endosomal pH where iron dissociates from transferrin). Targeted knock-in FLAG-tagged ZIP14 in HepG2 cells; confocal immunofluorescence; siRNA knockdown; iron assimilation assays; pH-dependent transport assay The Journal of biological chemistry High 20682781
2010 SLC39A14/ZIP14 splicing is regulated by the Wnt/β-catenin pathway in colorectal cancer; β-catenin knockdown or dominant-negative TCF expression alters the exon 4A/4B isoform ratio. The splicing factors SRSF1 and its kinase SRPK1 mediate this regulation, with SRSF1 binding preferentially to exon 4B. β-catenin siRNA knockdown, dominant-negative TCF overexpression in DLD1 and Ls174T cells; siRNA knockdown of SRPK1 and SRSF1; exon array and RT-PCR; in silico splicing factor binding analysis Molecular & cellular proteomics : MCP Medium 20938052
2011 ZIP14 is a broad-scope metal-ion transporter that specifically transports Fe2+ (not Fe3+), with K0.5 ≈ 2 µM; transport is saturable, temperature-dependent, pH-sensitive, Ca2+-dependent, stimulated by HCO3-, and inhibited by Co2+, Mn2+, Zn2+. ZIP14 also transports Cd2+, Mn2+, Zn2+ (K0.5 ≈ 2 µM for Zn2+) but not Cu (I or II). The inhibition profiles and Ca2+ dependence differ between Fe2+ and Zn2+ transport. Xenopus laevis oocyte heterologous expression system; radioisotope transport assays (55Fe, 109Cd, 54Mn, 65Zn, 64Cu); kinetic analysis; temperature, pH, ion dependence assays American journal of physiology. Cell physiology High 21653899
2011 SLC39A14/ZIP14 controls GPCR-mediated cAMP-CREB signaling by suppressing basal phosphodiesterase (PDE) activity. Zip14 KO mice show reduced cAMP due to increased PDE activity, causing impaired GPCR signaling in growth plate, pituitary, and liver, resulting in growth retardation and impaired gluconeogenesis. Slc39a14 knockout mouse model; cAMP measurement; PDE activity assay; CREB phosphorylation analysis; growth and gluconeogenesis phenotyping PloS one Medium 21445361
2012 ZIP14 localizes to the basolateral membrane of enterocytes and is present in endosomes; it is involved in endosomal trafficking of zinc. Zip14 KO mice show zinc trapped in endosomes and reduced threonine phosphorylation of tight junction protein occludin, impairing intestinal barrier function. Plasma membrane fractionation; endosome isolation; FluoZin-3AM fluorescence for endosomal zinc; intestinal permeability assays (FITC-dextran); occludin phosphorylation; claudin 1/2 expression American journal of physiology. Gastrointestinal and liver physiology Medium 25428902
2012 ZIP14 mediates hepatic zinc uptake during liver regeneration, inhibiting PTP1B phosphatase activity through increased intracellular zinc, which in turn enhances c-Met phosphorylation and hepatocyte proliferation. Zip14 KO mice fail to show increased hepatic zinc or hepatocyte proliferation after partial hepatectomy. Partial hepatectomy in WT and Zip14 KO mice; Zip14-overexpressing AML12 hepatocytes; PTP1B activity assay; c-Met phosphorylation; proliferation markers (PCNA, CyclinD1, Ki67); hepatic zinc measurement Gastroenterology High 22374166
2012 ZIP8 and ZIP14 both mediate apical uptake of Cd2+ and Mn2+ in kidney proximal tubule cells; siRNA knockdown of either reduces uptake from the apical membrane. ZIP8 and ZIP14 are expressed in the S3 segment of proximal tubules. siRNA knockdown of ZIP8, ZIP14, DMT1 in proximal tubule cell Transwell culture; apical/basolateral metal uptake assays; in situ hybridization Metallomics : integrated biometal science Medium 22534978
2012 ZIP14 in the Xenopus oocyte system mediates electroneutral divalent cation/bicarbonate symport (confirmed by electrogenicity studies using a potassium gradient). ZIP14A and ZIP14B show distinct metal-ion inhibition patterns for Cd and Zn uptake. Xenopus oocyte expression; Km/Vmax determination; electrogenicity studies with potassium gradient; competitive inhibition with 10 divalent cations Metallomics : integrated biometal science High 23090441
2012 ZIP14 mediates zinc uptake in macrophages in response to LPS; Zip14 knockdown attenuates cytokine production, indicating ZIP14 has a buffering role in macrophage inflammatory responses. LPS induction of ZIP14 depends on calcium signaling, GC-rich DNA binding, and NF-κB downregulation. LPS treatment of primary human macrophages; siRNA knockdown; cytokine mRNA (RT-qPCR) and protein measurement; pharmacological inhibitors of calcium signaling and NF-κB Inflammation research Medium 23052185
2013 ZIP14 protein is localized to the basolateral membrane of hepatocytes and to acinar cells of the pancreas; its protein levels are upregulated in iron-loaded animals (post-translationally, as mRNA does not change with iron status), while DMT1 is regulated oppositely. Confocal immunofluorescence microscopy; immunoblotting; qRT-PCR in iron-deficient, adequate, and overloaded rats; hypotransferrinemic mice Haematologica Medium 23349308
2014 ZIP14 undergoes endocytosis, membrane extraction, deglycosylation, and proteasomal degradation via a pathway independent of ER-associated protein degradation (ERAD). Iron inhibits membrane extraction of internalized ZIP14, resulting in higher steady-state levels. N-linked glycosylation at N102 is required for efficient membrane extraction and iron-sensitive degradation of ZIP14. Inhibitor studies (proteasome inhibitors, retrograde trafficking inhibitors, bafilomycin); glycosylation mutants (N102 substitution); pulse-chase and protein stability assays; endocytosis assays Proceedings of the National Academy of Sciences of the United States of America High 24927598
2014 IL-6 upregulates ZIP14 in SH-SY5Y neuronal cells, increasing Mn2+ uptake; siRNA knockdown of ZIP14 reduces Mn2+ uptake. IL-6 also downregulates ZnT10, reducing Mn excretion. Combined effect enhances Mn accumulation in neuronal cells. siRNA knockdown of ZIP14, ZIP8, ZnT10 in SH-SY5Y cells; IL-6 treatment; Mn uptake assays; mRNA and protein quantification Metallomics : integrated biometal science Medium 24576911
2015 SLC39A14 ablation in mice markedly reduces NTBI uptake by liver and pancreas. In hemochromatosis mouse models (Hfe-/- and Hfe2-/-), Slc39a14 deficiency greatly diminishes hepatic and pancreatic iron loading and prevents iron deposition in hepatocytes and pancreatic acinar cells. Slc39a14 KO mice crossed with Hfe-/- and Hfe2-/- mice; plasma NTBI uptake measurements; tissue iron quantification; histology Cell metabolism High 26028554
2015 Prion protein (PrPC) functions as a ferrireductase partner for ZIP14 (and DMT1); coexpression of PrPC with ZIP14 in HepG2 cells increases uptake of Fe3+ (not Fe2+), suggesting PrPC reduces Fe3+ to Fe2+ for transport through ZIP14. PrPC knockout mice with 59Fe radiolabeling; HepG2 cell overexpression; ferric vs ferrous iron uptake assays; coexpression studies Free radical biology & medicine Medium 25862412
2016 ZIP14 is upregulated in cachectic skeletal muscles by TNF-α and TGF-β cytokines. ZIP14-mediated zinc uptake in muscle progenitor cells represses MyoD and Mef2c expression, blocking muscle-cell differentiation. In differentiated muscle cells, ZIP14-mediated zinc accumulation induces myosin heavy chain loss. Germline or muscle-specific Zip14 depletion reduces muscle atrophy in metastatic cancer models. Cancer cachexia mouse models (metastatic colon, lung, breast); germline and muscle-specific Zip14 KO; cytokine treatment (TNF-α, TGF-β); MyoD and Mef2c mRNA/protein; myosin heavy chain measurement; zinc measurement Nature medicine High 29875463
2016 ZIP14 is localized on the plasma membrane of human β-cells (primary islets and βlox5 cell line) and mediates ~50% of NTBI uptake in these cells; siRNA knockdown of ZIP14 reduces NTBI uptake by 50% in both cell systems. siRNA knockdown in βlox5 cells and primary human islets; NTBI uptake assays; overexpression of ZIP14, ZIP8, DMT1; immunofluorescence American journal of physiology. Cell physiology Medium 27903581
2016 ZIP14 undergoes sequential translocation from the plasma membrane to early and late endosomes during glucose uptake in hepatocytes. ZIP14-mediated zinc transport delivers zinc to endosomes where it supports activity of zinc-dependent insulin-degrading enzyme (IDE) and cathepsin D to regulate insulin receptor activity. Zip14 KO mice show zinc-deficient endosomes, impaired IDE/cathepsin D activity, enhanced insulin receptor signaling, increased glycogen synthesis, and impaired gluconeogenesis. Zip14 KO mouse hepatocytes; endosome fractionation; zinc measurement in endosomes; IDE and cathepsin D activity assays; insulin receptor phosphorylation; glycogen synthesis and gluconeogenesis assays; live cell imaging of ZIP14 localization The Journal of biological chemistry High 27703010
2017 p53 interacts with ZIP14 protein, increases its ubiquitination, and promotes its degradation, thereby reducing ZIP14 protein levels post-translationally. Loss of p53 results in higher ZIP14 levels and increased NTBI uptake. Co-precipitation (p53-ZIP14 interaction); ubiquitination assay; p53 overexpression/knockdown; NTBI uptake assays; immunoblotting Nutrients Medium 29292794
2017 Hepatic ZIP14 mediates zinc import required for adaptation to ER stress; ZIP14-mediated zinc inhibits PTP1B activity to suppress apoptosis and steatosis. During ER stress, transcription factors ATF4 and ATF6α transcriptionally upregulate Zip14. Zip14 KO mice under ER stress show greater PTP1B activity, proapoptotic protein expression, and hepatic steatosis. Pharmacologic and HFD-induced ER stress in Zip14 KO mice; ATF4/ATF6α overexpression; PTP1B activity assay; apoptosis markers; steatosis quantification Proceedings of the National Academy of Sciences of the United States of America High 28673968
2017 Slc39a14 global knockout mice develop markedly increased Mn in brain and extrahepatic tissues with motor deficits reversible by Na2CaEDTA chelation. Hepatocyte-specific Slc39a14 KO mice do not accumulate Mn in brain under normal conditions, indicating hepatocyte-autonomous loss of ZIP14 is insufficient to cause brain Mn accumulation; non-hepatic ZIP14 expression is required to prevent systemic Mn overload. Global and hepatocyte-specific (Alb-Cre) Slc39a14 KO mice; ICP-MS for tissue metal levels; motor deficit assays; chelation rescue Cell discovery High 28751976
2018 ZIP14 mediates Mn2+ uptake in brain microvascular endothelial cells (BMVECs) at both apical (blood) and basal (brain) sides, supporting bidirectional Mn flux across the blood-brain barrier. Knockdown of ZIP14 (and ZIP8) reduces Mn uptake; uptake is pH-, bicarbonate-, and LPS-dependent. siRNA knockdown of ZIP8 and ZIP14 in BMVECs; surface protein biotinylation; 54Mn uptake; kinetic analysis; LPS treatment; apical/basolateral transport assays The Journal of biological chemistry Medium 31699897
2018 A dominant gain-of-function mutation (L441R) in ZIP14 prevents its trafficking to the plasma membrane and causes intracellular zinc accumulation, leading to hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts exhibit enhanced endosteal cortical bone formation with osteoporotic trabecular bone, causing Hyperostosis Cranialis Interna-like phenotype. Whole-exome sequencing (patient); conditional knock-in mouse (osteoblast-specific L438R); subcellular localization assay; zinc measurement; cAMP-CREB and NFAT signaling assays; bone histomorphometry PLoS genetics High 29621230
2019 Intestinal ZIP14 acts primarily as a basolateral transporter in enterocytes that mediates direct basolateral reuptake of freshly absorbed manganese, thereby restricting net absorptive manganese transport. Loss of intestinal ZIP14 impairs secretory (basolateral-to-apical) Mn transport and enhances absorptive (apical-to-basolateral) Mn transport. Intestine-specific Zip14 KO mice accumulate Mn in liver and brain. CaCo-2 Transwell model; ZIP14-deficient CaCo-2 cells (CRISPR); directional Mn transport assays; intestine-specific Zip14 KO mice; ICP-MS The Journal of biological chemistry High 31028174
2019 ZIP14 in brain microvascular endothelial cells has plasma membrane occupancy regulated by cytoplasmic Ca2+ via the Golgi Ca2+-ATPase SPCA1. RNAi knockdown of SPCA1 increases cytoplasmic Ca2+, which enhances membrane localization of ZIP14 and increases 54Mn2+ uptake; SPCA1 overexpression has opposite effects. Surface protein biotinylation; indirect immunofluorescence; GFP-tagged proteins; SPCA1 RNAi knockdown; Ca2+ chelation; 54Mn2+ uptake assays The Journal of biological chemistry Medium 35787370
2019 ZIP14 is degraded in response to Mn exposure via a lysosomal pathway (blocked by bafilomycin A1, which increased ZIP14 in LAMP1-positive vesicles), providing a cytoprotective feedback mechanism to limit Mn uptake. ZIP14 is localized to the basolateral surface of polarized HepaRG hepatocytes. Western blot and immunofluorescence in polarized HepaRG cells; 54Mn uptake (time- and temperature-dependent); bafilomycin A1 inhibition; LAMP1 co-localization Biometals Medium 31541377
2020 Zip14 deletion in skeletal muscle results in muscle wasting at basal steady state associated with increased p-Mef2c, Hspb7, p38 activation, and NF-κB binding to the Mef2c promoter. Zip14-mediated zinc uptake in muscle during LPS inflammation increases Atrogin1/MuRF1 and reduces MyoD (cachexia signatures). miR-675-3p and -5p induction by LPS is Zip14-dependent. Zip14 global KO mice; LPS-induced inflammation; microarray and qPCR; ChIP (NF-κB at Mef2c promoter); p38 phosphorylation; Atrogin1/MuRF1/MyoD protein levels Scientific reports Medium 32132660
2022 Enterocyte-specific ZIP14 ablation reduces HDAC3 (and total HDAC) activity, leading to epigenetic dysregulation of tight junction and cytokine genes (claudin 1, 2, IL-6, IFNγ). NF-κB, STAT3, and CDX2 show increased binding to promoters of dysregulated genes. Zinc supplementation of organoids from ΔIECZip14 mice restores differential gene expression. Enterocyte-specific Zip14 KO mice; RNA sequencing; ChIP for NF-κB, STAT3, CDX2; HDAC activity assays; intestinal organoids with zinc supplementation American journal of physiology. Gastrointestinal and liver physiology High 36537699
2022 Combined intestinal and hepatic ZIP14 deletion (double KO) causes much greater manganese overload than single-tissue deletion alone, demonstrating that both intestinal and hepatic ZIP14 cooperate to maintain systemic Mn homeostasis. Intestine-specific, liver-specific, and double (intestine+liver) Zip14 KO mice; ICP-MS for tissue Mn International journal of molecular sciences Medium 35742937
2023 In pancreatic β cells, ZIP14 localizes on the endoplasmic reticulum (not plasma membrane) and functions as a negative regulator of glucose-stimulated insulin secretion by regulating intracellular zinc trafficking. β cell-specific Zip14 KO mice show greater glucose-stimulated insulin secretion, increased energy expenditure, and on HFD develop greater islet hyperplasia and compensatory hyperinsulinemia. β cell-specific Zip14 KO mice; ZIP14 localization by immunofluorescence (co-staining with ER marker); glucose-stimulated insulin secretion (in vivo, ex vivo islets, MIN6 cells); zinc measurement; metabolic phenotyping American journal of physiology. Endocrinology and metabolism High 38019082
2024 Enterocyte-specific ZIP14 deletion reduces cellular labile zinc, causing chromatin remodeling (closed chromatin at MHCII gene regulatory regions) and decreased expression of MHCII molecules and their master transactivator CIITA. Zinc supplementation of Zip14 KO organoids restores MHCII transcript levels. Enterocyte-specific Zip14 KO; RNA sequencing; ChIP with CIITA antibody; ATAC-seq; FluoZin-3 zinc measurement; organoid zinc supplementation rescue; western blot, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 39793074
2024 In liver fibrosis, zinc supplementation increases ZIP14 expression via MTF1 transcription factor binding to the ZIP14 promoter and reduction of HDAC4 binding, establishing an epigenetic mechanism by which zinc regulates ZIP14 expression in hepatocytes. CCl4-induced liver fibrosis mouse model; ZnCl2 treatment; ChIP for MTF1 and HDAC4 at ZIP14 promoter; ZIP14 expression; intracellular zinc measurement Biological trace element research Medium 38221603

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proceedings of the National Academy of Sciences of the United States of America 454 16950869
2005 Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proceedings of the National Academy of Sciences of the United States of America 443 15863613
2008 Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. Molecular pharmacology 277 18270315
2015 SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis. Cell metabolism 193 26028554
2011 Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. American journal of physiology. Cell physiology 189 21653899
2012 Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics : integrated biometal science 166 22534978
2018 Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle. Nature medicine 150 29875463
2013 ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders. Haematologica 147 23349308
2005 Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. FEBS letters 144 15642354
2011 The zinc transporter SLC39A14/ZIP14 controls G-protein coupled receptor-mediated signaling required for systemic growth. PloS one 143 21445361
2012 Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia). PloS one 141 23110240
2010 ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. The Journal of biological chemistry 135 20682781
2018 The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14). The Journal of nutrition 107 29490098
2017 Manganese transporter Slc39a14 deficiency revealed its key role in maintaining manganese homeostasis in mice. Cell discovery 107 28751976
2014 Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function. American journal of physiology. Gastrointestinal and liver physiology 94 25428902
2010 Alternative splicing of SLC39A14 in colorectal cancer is regulated by the Wnt pathway. Molecular & cellular proteomics : MCP 75 20938052
2017 Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress. Proceedings of the National Academy of Sciences of the United States of America 69 28673968
2012 The zinc transporter Zip14 influences c-Met phosphorylation and hepatocyte proliferation during liver regeneration in mice. Gastroenterology 69 22374166
2008 The hereditary hemochromatosis protein, HFE, inhibits iron uptake via down-regulation of Zip14 in HepG2 cells. The Journal of biological chemistry 69 18524764
2015 Prion protein functions as a ferrireductase partner for ZIP14 and DMT1. Free radical biology & medicine 68 25862412
2020 The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis. International journal of molecular sciences 66 32392784
2015 Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation. American journal of physiology. Gastrointestinal and liver physiology 63 26272258
2015 Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity. American journal of physiology. Endocrinology and metabolism 62 26646099
2012 ZIP14 zinc transporter downregulation and zinc depletion in the development and progression of hepatocellular cancer. Journal of gastrointestinal cancer 62 21373779
2019 The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. The Journal of biological chemistry 60 31028174
2022 ZIP14 is involved in iron deposition and triggers ferroptosis in diabetic nephropathy. Metallomics : integrated biometal science 59 35641158
2009 Interleukin-1beta contributes via nitric oxide to the upregulation and functional activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes. American journal of physiology. Gastrointestinal and liver physiology 59 19179618
2016 The plasma membrane metal-ion transporter ZIP14 contributes to nontransferrin-bound iron uptake by human β-cells. American journal of physiology. Cell physiology 58 27903581
2012 ZIP14 and ZIP8 zinc/bicarbonate symporters in Xenopus oocytes: characterization of metal uptake and inhibition. Metallomics : integrated biometal science 56 23090441
2014 An iron-regulated and glycosylation-dependent proteasomal degradation pathway for the plasma membrane metal transporter ZIP14. Proceedings of the National Academy of Sciences of the United States of America 54 24927598
2019 Iron uptake by ZIP8 and ZIP14 in human proximal tubular epithelial cells. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 51 30806852
2016 Hepatic ZIP14-mediated Zinc Transport Contributes to Endosomal Insulin Receptor Trafficking and Glucose Metabolism. The Journal of biological chemistry 50 27703010
2005 SLC39A14, a LZT protein, is induced in adipogenesis and transports zinc. The FEBS journal 50 15794747
2018 Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system. Orphanet journal of rare diseases 47 29382362
2019 The solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels. The Journal of biological chemistry 42 31699897
2018 Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies. Molecular genetics and metabolism 41 29685658
2012 Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 39 23052185
2017 Iron importers Zip8 and Zip14 are expressed in retina and regulated by retinal iron levels. Experimental eye research 38 28057442
2014 Interleukin-6 enhances manganese accumulation in SH-SY5Y cells: implications of the up-regulation of ZIP14 and the down-regulation of ZnT10. Metallomics : integrated biometal science 36 24576911
2017 The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14. Nutrients 34 29292794
2018 Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 33 29895370
2024 Inhibition of Slc39a14/Slc39a8 reduce vascular calcification via alleviating iron overload induced ferroptosis in vascular smooth muscle cells. Cardiovascular diabetology 32 38812011
2018 A novel mutation in SLC39A14 causing hypermanganesemia associated with infantile onset dystonia. The journal of gene medicine 32 29498153
2018 Autosomal-recessive iron deficiency anemia, dystonia and hypermanganesemia caused by new variant mutation of the manganese transporter gene SLC39A14. Acta neurologica Belgica 29 30232769
2014 Psychological stress induced zinc accumulation and up-regulation of ZIP14 and metallothionein in rat liver. BMC gastroenterology 29 24548602
2017 Concentration-dependent roles of DMT1 and ZIP14 in cadmium absorption in Caco-2 cells. The Journal of toxicological sciences 27 28904291
2014 Tissue-Specific Induction of Mouse ZIP8 and ZIP14 Divalent Cation/Bicarbonate Symporters by, and Cytokine Response to, Inflammatory Signals. International journal of toxicology 27 24728862
2020 Circular RNA circ_001842 plays an oncogenic role in renal cell carcinoma by disrupting microRNA-502-5p-mediated inhibition of SLC39A14. Journal of cellular and molecular medicine 26 32729666
2014 Cellular localization and developmental changes of Zip8, Zip14 and transferrin receptor 1 in the inner ear of rats. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 26 25007852
2020 Astrocytic expression of ZIP14 (SLC39A14) is part of the inflammatory reaction in chronic neurodegeneration with iron overload. Glia 25 32077535
2020 Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7. Scientific reports 25 32132660
2019 Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia. Cancers 25 31861290
2023 Knockdown of SLC39A14 inhibits glioma progression by promoting erastin-induced ferroptosis SLC39A14 knockdown inhibits glioma progression. BMC cancer 22 37978473
2019 Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14. Nutrients 22 31261654
2024 Mesenchymal Stem Cells Prevent SLC39A14-Dependent Hepatocyte Ferroptosis through Exosomal miR-16-5p in Liver Graft. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 39680749
2020 Human placental cell line HTR-8/SVneo accumulates cadmium by divalent metal transporters DMT1 and ZIP14. Metallomics : integrated biometal science 21 33146651
2018 Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption. FEBS open bio 20 29632817
2018 Long-Term High-Fat Diet Decreases Hepatic Iron Storage Associated with Suppressing TFR2 and ZIP14 Expression in Rats. Journal of agricultural and food chemistry 20 30350980
2012 The exon-level biomarker SLC39A14 has organ-confined cancer-specificity in colorectal cancer. International journal of cancer 20 22173985
2017 Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters ZIP14 and ZNT1 in Obesity and Polycystic Ovary Syndrome. Frontiers in endocrinology 19 28303117
2022 Effect of Chelation Therapy on a Korean Patient With Brain Manganese Deposition Resulting From a Compound Heterozygous Mutation in the SLC39A14 Gene. Journal of movement disorders 18 35306789
2022 Enterocyte-specific deletion of metal transporter Zip14 (Slc39a14) alters intestinal homeostasis through epigenetic mechanisms. American journal of physiology. Gastrointestinal and liver physiology 17 36537699
2020 Localization of ZIP14 and ZIP8 in HIBCPP Cells. Brain sciences 17 32784388
2019 Berberine induces ZIP14 expression and modulates zinc redistribution to protect intestinal mucosal barrier during polymicrobial sepsis. Life sciences 17 31351968
2019 Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice. Nutrients 17 31487869
2018 Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis. PLoS genetics 17 29621230
2022 The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice. International journal of molecular sciences 16 35742937
2021 HIF-1α Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular Zn2+ Accumulation in Inflammatory Synoviocytes. International journal of molecular sciences 16 34198528
2021 Behavioral and neurochemical studies of inherited manganese-induced dystonia-parkinsonism in Slc39a14-knockout mice. Neurobiology of disease 15 34358615
2019 ZIP14 is degraded in response to manganese exposure. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 15 31541377
2022 Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish. Disease models & mechanisms 14 35514229
2023 Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism. American journal of physiology. Gastrointestinal and liver physiology 13 37873588
2024 RELA-mediated upregulation of LINC03047 promotes ferroptosis in silica-induced pulmonary fibrosis via SLC39A14. Free radical biology & medicine 12 39111583
2022 Calcium and the Ca-ATPase SPCA1 modulate plasma membrane abundance of ZIP8 and ZIP14 to regulate Mn(II) uptake in brain microvascular endothelial cells. The Journal of biological chemistry 12 35787370
2022 Hereditary Disorders of Manganese Metabolism: Pathophysiology of Childhood-Onset Dystonia-Parkinsonism in SLC39A14 Mutation Carriers and Genetic Animal Models. International journal of molecular sciences 11 36361624
2021 Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats. Biology 11 34356508
2024 Dihydroartemisinin Sensitizes Lung Cancer Cells to Cisplatin Treatment by Upregulating ZIP14 Expression and Inducing Ferroptosis. Cancer medicine 10 39394878
2021 Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload in Zip14-/- Mice. International journal of molecular sciences 10 34202493
2016 Hepatic mobilization of zinc after an experimental surgery, and its relationship with inflammatory cytokines release, and expression of metallothionein and Zip14 transporter. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 10 27785531
2024 Expression of Manganese Transporters ZIP8, ZIP14, and ZnT10 in Brain Barrier Tissues. International journal of molecular sciences 9 39408669
2023 A novel homozygous SLC39A14 variant in an infant with hypermanganesemia and a review of the literature. Frontiers in pediatrics 9 36733764
2022 Pathophysiological studies of aging Slc39a14 knockout mice to assess the progression of manganese-induced dystonia-parkinsonism. Neurotoxicology 9 36152728
2023 Absence of Slc39a14/Zip14 in mouse pancreatic beta cells results in hyperinsulinemia. American journal of physiology. Endocrinology and metabolism 8 38019082
2025 Metal ion transporter SLC39A14-mediated ferroptosis and glycosylation modulate the tumor immune microenvironment: pan-cancer multi-omics exploration of therapeutic potential. Cancer cell international 7 41121066
2024 The Role of Zinc on Liver Fibrosis by Modulating ZIP14 Expression Throughout Epigenetic Regulatory Mechanisms. Biological trace element research 7 38221603
2024 SLC39A14 promotes the development of esophageal squamous cell carcinoma through PI3K/Akt/mTOR signaling pathway. International immunopharmacology 7 39700956
2013 Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation. Toxicology letters 7 23353815
2008 Restraint stress up-regulates expression of zinc transporter Zip14 mRNA in mouse liver. Cytotechnology 7 19003164
2024 IRG1/Itaconate inhibits hepatic stellate cells ferroptosis and attenuates TAA-induced liver fibrosis by regulating SLC39A14 expression. International immunopharmacology 6 39724735
2020 Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1-deficient mouse model of breast cancer metastasis. Cancer medicine 6 32730698
2025 SOX4-ZIP14-zinc metabolism mediates oncogenesis and suppresses T cell immunity in nasopharyngeal carcinoma. Cell reports. Medicine 5 40818459
2022 Heterogeneous Immunolocalisation of Zinc Transporters ZIP6, ZIP10 and ZIP14 in Human Normo- and Asthenozoospermic Spermatozoa. Current issues in molecular biology 5 36005133
2024 The mechanism by which piR-000699 targets SLC39A14 regulates ferroptosis in aging myocardial ischemia/reperfusion injury. Acta biochimica et biophysica Sinica 4 38439666
2024 Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 4 39793074
2022 Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14. Oxidative medicine and cellular longevity 4 36062189
2022 Long Noncoding RNA, MicroRNA, Zn Transporter Zip14 (Slc39a14) and Inflammation in Mice. Nutrients 4 36501144
2024 ZIP14 Affects the Proliferation, Apoptosis, and Migration of Cervical Cancer Cells by Regulating the P38 MAPK Pathway. Current cancer drug targets 3 37990424
2024 Genetic control of MRI contrast using the manganese transporter Zip14. Magnetic resonance in medicine 3 38573932
2022 Transcriptional Regulation and Protein Localization of Zip10, Zip13 and Zip14 Transporters of Freshwater Teleost Yellow Catfish Pelteobagrus fulvidraco Following Zn Exposure in a Heterologous HEK293T Model. International journal of molecular sciences 3 35887381
2024 ZIP8 Is Upregulated in the Testis of Zip14-/- Mice. Nutrients 2 39519408

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