Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Cell Physiol
2011 Oct 01;3014:C862-71. doi: 10.1152/ajpcell.00479.2010.
Show Gene links
Show Anatomy links
Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron.
Pinilla-Tenas JJ
,
Sparkman BK
,
Shawki A
,
Illing AC
,
Mitchell CJ
,
Zhao N
,
Liuzzi JP
,
Cousins RJ
,
Knutson MD
,
Mackenzie B
.
???displayArticle.abstract???
Recent studies have shown that overexpression of the transmembrane protein Zrt- and Irt-like protein 14 (Zip14) stimulates the cellular uptake of zinc and nontransferrin-bound iron (NTBI). Here, we directly tested the hypothesis that Zip14 transports free zinc, iron, and other metal ions by using the Xenopus laevis oocyte heterologous expression system, and use of this approach also allowed us to characterize the functional properties of Zip14. Expression of mouse Zip14 in RNA-injected oocytes stimulated the uptake of (55)Fe in the presence of l-ascorbate but not nitrilotriacetic acid, indicating that Zip14 is an iron transporter specific for ferrous ion (Fe(2+)) over ferric ion (Fe(3+)). Zip14-mediated (55)Fe(2+) uptake was saturable (K(0.5) ≈ 2 μM), temperature-dependent (apparent activation energy, E(a) = 15 kcal/mol), pH-sensitive, Ca(2+)-dependent, and inhibited by Co(2+), Mn(2+), and Zn(2+). HCO(3)(-) stimulated (55)Fe(2+) transport. These properties are in close agreement with those of NTBI uptake in the perfused rat liver and in isolated hepatocytes reported in the literature. Zip14 also mediated the uptake of (109)Cd(2+), (54)Mn(2+), and (65)Zn(2+) but not (64)Cu (I or II). (65)Zn(2+) uptake also was saturable (K(0.5) ≈ 2 μM) but, notably, the metal-ion inhibition profile and Ca(2+) dependence of Zn(2+) transport differed from those of Fe(2+) transport, and we propose a model to account for these observations. Our data reveal that Zip14 is a complex, broad-scope metal-ion transporter. Whereas zinc appears to be a preferred substrate under normal conditions, we found that Zip14 is capable of mediating cellular uptake of NTBI characteristic of iron-overload conditions.
Andrews,
Disorders of iron metabolism.
1999, Pubmed
Andrews,
Disorders of iron metabolism.
1999,
Pubmed
Barisani,
Evidence for a low Km transporter for non-transferrin-bound iron in isolated rat hepatocytes.
1995,
Pubmed
Canonne-Hergaux,
Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood cells of normal and anemic mk/mk mice.
2001,
Pubmed
Collins,
Functional and molecular characterization of NHE3 expression during ontogeny in rat jejunal epithelium.
1997,
Pubmed
Cousins,
Mammalian zinc transport, trafficking, and signals.
2006,
Pubmed
Cragg,
A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane.
2002,
Pubmed
,
Xenbase
Dufner-Beattie,
The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice.
2003,
Pubmed
Dufner-Beattie,
Structure, function, and regulation of a subfamily of mouse zinc transporter genes.
2003,
Pubmed
Eide,
The SLC39 family of metal ion transporters.
2004,
Pubmed
Eng,
Sequence analyses and phylogenetic characterization of the ZIP family of metal ion transport proteins.
1998,
Pubmed
Gaither,
Functional expression of the human hZIP2 zinc transporter.
2000,
Pubmed
Gao,
The hereditary hemochromatosis protein, HFE, inhibits iron uptake via down-regulation of Zip14 in HepG2 cells.
2008,
Pubmed
Girijashanker,
Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter.
2008,
Pubmed
Grootveld,
Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy.
1989,
Pubmed
Gunshin,
Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver.
2005,
Pubmed
Hershko,
Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity.
1978,
Pubmed
Inman,
Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport.
1994,
Pubmed
Jordan,
The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity.
1994,
Pubmed
Knutson,
Iron-sensing proteins that regulate hepcidin and enteric iron absorption.
2010,
Pubmed
Lichten,
Interleukin-1beta contributes via nitric oxide to the upregulation and functional activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes.
2009,
Pubmed
Lichten,
Mammalian zinc transporters: nutritional and physiologic regulation.
2009,
Pubmed
Lin,
Selective electrodiffusion of zinc ions in a Zrt-, Irt-like protein, ZIPB.
2010,
Pubmed
Liuzzi,
Mammalian zinc transporters.
2004,
Pubmed
Liuzzi,
Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response.
2005,
Pubmed
Liuzzi,
Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells.
2006,
Pubmed
Mackenzie,
Iron Imports. II. Iron uptake at the apical membrane in the intestine.
2005,
Pubmed
Mackenzie,
Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes.
2006,
Pubmed
,
Xenbase
Mackenzie,
Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1).
2007,
Pubmed
,
Xenbase
McEwan,
The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo.
1988,
Pubmed
McEwan,
A combined TDDA-PVC pH and reference electrode for use in the upper small intestine.
1990,
Pubmed
Moridani,
Iron complexes of deferiprone and dietary plant catechols as cytoprotective superoxide radical scavengers(1).
2001,
Pubmed
Nomura,
Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.
1994,
Pubmed
Núñez,
Mobilization of iron from endocytic vesicles. The effects of acidification and reduction.
1990,
Pubmed
Pattison,
Kinetics of zinc uptake and exchange by primary cultures of rat hepatocytes.
1986,
Pubmed
Romero-Calvo,
Reversible Ponceau staining as a loading control alternative to actin in Western blots.
2010,
Pubmed
Shawki,
Interaction of calcium with the human divalent metal-ion transporter-1.
2010,
Pubmed
,
Xenbase
Taylor,
Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14.
2005,
Pubmed
Thompson,
Iron absorption by Belgrade rat pups during lactation.
2007,
Pubmed
Wang,
The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells.
2004,
Pubmed
Wright,
Characterization of non-transferrin-bound iron clearance by rat liver.
1986,
Pubmed
Zhao,
ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin.
2010,
Pubmed
de Valk,
Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes.
2000,
Pubmed
