Enzymes
UniProtKB help_outline | 1,065 proteins |
Reaction participants Show >> << Hide
- Name help_outline hydrogencarbonate Identifier CHEBI:17544 (Beilstein: 3903504; CAS: 71-52-3) help_outline Charge -1 Formula CHO3 InChIKeyhelp_outline BVKZGUZCCUSVTD-UHFFFAOYSA-M SMILEShelp_outline OC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 58 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline Mn2+ Identifier CHEBI:29035 (CAS: 16397-91-4) help_outline Charge 2 Formula Mn InChIKeyhelp_outline WAEMQWOKJMHJLA-UHFFFAOYSA-N SMILEShelp_outline [Mn++] 2D coordinates Mol file for the small molecule Search links Involved in 11 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:62260 | RHEA:62261 | RHEA:62262 | RHEA:62263 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family: characterization of transporter properties.
He L., Girijashanker K., Dalton T.P., Reed J., Li H., Soleimani M., Nebert D.W.
Cadmium is a dangerous metal distributed widely in the environment. Members of our laboratory recently identified the ZIP8 transporter protein, encoded by the mouse Slc39a8 gene, to be responsible for genetic differences in response to cadmium damage of the testis. Stable retroviral infection of t ... >> More
Cadmium is a dangerous metal distributed widely in the environment. Members of our laboratory recently identified the ZIP8 transporter protein, encoded by the mouse Slc39a8 gene, to be responsible for genetic differences in response to cadmium damage of the testis. Stable retroviral infection of the ZIP8 cDNA in mouse fetal fibroblast cultures (rvZIP8 cells) leads to as much as a 10-fold increase in the rate of intracellular cadmium influx and accumulation. In the present study, we showed that cadmium uptake operated maximally at pH 7.5 and a temperature of 37 degrees C and was inhibited by cyanide. Of more than a dozen cations tested, manganese(II) was the best competitive cation for cadmium uptake. The Km for Cd2+ uptake was 0.62 microM, and the Km for Mn2+ uptake was 2.2 microM; thus, manganese is probably the physiological substrate for ZIP8. Cadmium uptake was independent of sodium, potassium or chloride ions, but strongly dependent on the presence of bicarbonate. By Western blot analysis of rvZIP8 cells, we showed that ZIP8 protein was glycosylated. Using Z-stack confocal microscopy in Madin-Darby canine kidney polarized epithelial cells, we found that ZIP8 was localized on the apical side-implying an important role for manganese or cadmium uptake and disposition. It is likely that ZIP8 is a Mn2+/HCO3- symporter, that a HCO3-gradient across the plasma membrane acts as the driving force for manganese uptake, and that cadmium is a rogue hitchhiker displacing manganese to cause cadmium-associated disease. << Less
Mol. Pharmacol. 70:171-180(2006) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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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 J.J., Sparkman B.K., Shawki A., Illing A.C., Mitchell C.J., Zhao N., Liuzzi J.P., Cousins R.J., Knutson M.D., Mackenzie B.
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 ... >> More
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. << Less
Am. J. Physiol. 301:C862-C871(2011) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.