SLC39A5 Membrane Protein Introduction

Introduction of SLC39A5

Zinc transporter ZIP5 (short for ZIP-5), alternatively known as the Zrt- and Irt-like protein 5 or SLC39A5, is encoded by the SLC39A5 gene in human. The zinc transporter SLC39A5 is a member of the ZIP family of metal ion transporters, which is also known as solute carrier family 39 (SLC39). SLC39A5 expression is restricted to many tissues that are important for zinc homeostasis, including liver, kidney, pancreas, small intestine, colon, spleen, fetal liver, and fetal kidney. The sequence of SLC39A5 protein is similar to the SLC39A4 protein.

Basic Information of SLC39A5
Protein Name Zinc transporter ZIP5
Gene Name SLC39A5
Aliases Solute carrier family 39 member 5, Zrt- and Irt-like protein 5, ZIP-5
Organism Homo sapiens (Human)
UniProt ID Q6ZMH5
Transmembrane Times 6
Length (aa) 540

Function of SLC39A5 Membrane Protein

Zrt- and Irt-like protein (ZIP) family has been thought to control the cytosolic concentration of zinc by transporting zinc into the cytoplasm from the extracellular space or from intracellular compartments. SLC39A5 is found in the basolateral membranes of pancreatic acinar cells and intestinal enterocytes, which are supposed to control zinc excretion from the body, and SLC39A5 proteins are internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. The zinc-regulation and basolateral localization of SLC39A5 in these cells are unique among the 14 members of the SLC39 family. The SLC39A5 protein may have an effect on polarized cells by carrying out serosal-to-mucosal zinc transport. It also plays a role in eye development. It can regulate extracellular matrix (ECM) proteins of the sclera and modulate the BMP/TGF-beta (bone morphogenetic protein/transforming growth factor-beta) signaling pathway. Co-expression of SLC39A4 and SLC39A5 in the intestine led to the hypothesis that these proteins play overlapping roles in the uptake of dietary zinc across the apical membrane of intestinal enterocytes.

Subcellular localization and the direction of zinc transport of ZnT and ZIP transporters. Fig.1 Subcellular localization and the direction of zinc transport of ZnT and ZIP transporters. (Kambe, 2015)

Application of SLC39A5 Membrane Protein in Literature

  1. Maares M., et al. Characterization of Caco-2 cells stably expressing the protein-based zinc probe eCalwy-5 as a model system for investigating intestinal zinc transport. J Trace Elem Med Biol. 2018, 49: 35-42. PubMed ID: 29895370

    Authors of this study attempt to reassure the presence of characteristic enterocyte-specific properties in the Caco-2-eCalwy clone and indicate that introduction of the additional zinc-binding protein in Caco-2 cells did not alter mRNA expression of the major intestinal zinc transporters, including ZIP5.

  2. Yin S., et al. Functional studies of Drosophila zinc transporters reveal the mechanism for zinc excretion in Malpighian tubules. BMC Biol. 2017, 15(1): 12. PubMed ID: 28196538

    Authors of this study demonstrate that knockdown of Zip71B/dZip5 or ZnT35C is able to mitigate stone formation, consistent with their roles in tubular zinc homeostasis.

  3. Li Q., et al. Knockdown of Zinc Transporter ZIP5 by RNA Interference Inhibits Esophageal Cancer Growth In Vivo. Oncol Res. 2016, 24(3): 205-14. PubMed ID: 27458102

    This article indicates that knocking down ZIP5 by small interfering RNA (siRNA) may be a new treatment strategy for esophageal cancer.

  4. Jin J., et al. Knockdown of zinc transporter ZIP5 (SLC39A5) expression significantly inhibits human esophageal cancer progression. Oncol Rep. 2015, 34(3): 1431-9. PubMed ID: 26133979

    This study aims to investigate the role of ZIP5 in esophageal cancer cells, and the results show that ZIP5 knockdown could inhibit cell progression in ESCC.

  5. Geiser J., et al. The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. PLoS One. 2013, 8(11): e82149. PubMed ID: 24303081

    Results of this study reveal that ZIP5 is involved in the control of zinc excretion in mice and functions in acinar cells to protect against zinc-induced acute pancreatitis.

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  1. Kambe T, et al. (2015). The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiological reviews. 95(3), pp.749-784.

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