RGD Reference Report - ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading.

Authors: Wang, Chia-Yu  Jenkitkasemwong, Supak  Duarte, Stephanie  Sparkman, Brian K  Shawki, Ali  Mackenzie, Bryan  Knutson, Mitchell D 
Citation: Wang CY, etal., J Biol Chem. 2012 Oct 5;287(41):34032-43. doi: 10.1074/jbc.M112.367284. Epub 2012 Aug 16.
RGD ID: 15090842
Pubmed: (View Article at PubMed) PMID:22898811
DOI: Full-text: DOI:10.1074/jbc.M112.367284

ZIP8 (SLC39A8) belongs to the ZIP family of metal-ion transporters. Among the ZIP proteins, ZIP8 is most closely related to ZIP14, which can transport iron, zinc, manganese, and cadmium. Here we investigated the iron transport ability of ZIP8, its subcellular localization, pH dependence, and regulation by iron. Transfection of HEK 293T cells with ZIP8 cDNA enhanced the uptake of (59)Fe and (65)Zn by 200 and 40%, respectively, compared with controls. Excess iron inhibited the uptake of zinc and vice versa. In RNA-injected Xenopus oocytes, ZIP8-mediated (55)Fe(2+) transport was saturable (K(0.5) of ∼0.7 μm) and inhibited by zinc. ZIP8 also mediated the uptake of (109)Cd(2+), (57)Co(2+), (65)Zn(2+) > (54)Mn(2+), but not (64)Cu (I or II). By using immunofluorescence analysis, we found that ZIP8 expressed in HEK 293T cells localized to the plasma membrane and partially in early endosomes. Iron loading increased total and cell-surface levels of ZIP8 in H4IIE rat hepatoma cells. We also determined by using site-directed mutagenesis that asparagine residues 40, 88, and 96 of rat ZIP8 are glycosylated and that N-glycosylation is not required for iron or zinc transport. Analysis of 20 different human tissues revealed abundant ZIP8 expression in lung and placenta and showed that its expression profile differs markedly from ZIP14, suggesting nonredundant functions. Suppression of endogenous ZIP8 expression in BeWo cells, a placental cell line, reduced iron uptake by ∼40%, suggesting that ZIP8 participates in placental iron transport. Collectively, these data identify ZIP8 as an iron transport protein that may function in iron metabolism.


Gene Ontology Annotations    

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Slc39a8  (solute carrier family 39 member 8)

Additional Information