title: Structure, function, and regulation of a subfamily of mouse zinc transporter genes.
abstract: Zinc is an essential metal for all eukaryotes, and cells have evolved a complex system of proteins to maintain the precise balance of zinc uptake, intracellular storage, and efflux. In mammals, zinc uptake appears to be mediated by members of the Zrt/Irt-like protein (ZIP) superfamily of metal ion transporters. Herein, we have studied a subfamily of zip genes (zip1, zip2, and zip3) that is conserved in mice and humans. These eight-transmembrane domain proteins contain a conserved 12-amino acid signature sequence within the fourth transmembrane domain. All three of these mouse ZIP proteins function to specifically increase the uptake of zinc in transfected cultured cells, similar to the previously demonstrated functions of human ZIP1 and ZIP2 (Gaither, L. A., and Eide, D. J. (2000) J. Biol. Chem. 275, 5560-5564; Gaither, L. A., and Eide, D. J. (2001) J. Biol. Chem. 276, 22258-22264). No ZIP3 orthologs have been previously studied. Furthermore, this first systematic comparative study of the in vivo expression and dietary zinc regulation of this subfamily of zip genes revealed that 1) zip1 mRNA is abundant in many mouse tissues, whereas zip2 and zip3 mRNAs are very rare or moderately rare, respectively, and tissue-restricted in their accumulation; and 2) unlike mouse metallothionein I and zip4 mRNAs (Dufner-Beattie, J., Wang, F., Kuo, Y.-M., Gitschier, J., Eide, D., and Andrews, G. K. (2003) J. Biol. Chem. 278, 33474-33481), the abundance of zip1, zip2, and zip3 mRNAs is not regulated by dietary zinc in the intestine and visceral endoderm, tissues involved in nutrient absorption. These studies suggest that all three of these ZIP proteins may play cell-specific roles in zinc homeostasis rather than primary roles in the acquisition of dietary zinc.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160-7421, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Dufner-Beattie
authors.forename: S Joshua
authors.initials: SJ
authors.lastname: Langmade
authors.forename: Fudi
authors.initials: F
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Eide
authors.forename: Glen K
authors.initials: GK
authors.lastname: Andrews
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D027682:Cation Transport Proteins; D002412:Cations; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D015032:Zinc / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002412:Cations; D018076:DNA, Complementary; D012333:RNA, Messenger; C403517:SLC39A1 protein, human; C498424:SLC39A2 protein, human; C106542:SLC39A3 protein, human; C485744:Slc39a1 protein, mouse; C498425:Slc39a2 protein, mouse; C498426:Slc39a3 protein, mouse; C017800:zinc-binding protein; D015032:Zinc