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SLC39A6 Membrane Protein Introduction

Introduction of SLC39A6

Zinc transporter ZIP6 (short for ZIP-6), alternatively known as estrogen-regulated protein LIV-1 or Zrt- and Irt-like protein 6, is encoded by the SLC39A6 gene in human. The zinc transporter SLC39A6 is a member of the ZIP (Zrt- and Irt-like protein) family of metal ion transporters, which is also called the solute carrier family 39 (SLC39). SLC39A6 is highly expressed in the breast, prostate, placenta, kidney, pituitary and corpus callosum, as well as in heart and intestine at a weak level. It has also been found in the cells derived from an adenocarcinoma of the lung and cervix carcinoma.

Basic Information of SLC39A6
Protein Name Zinc transporter ZIP6
Gene Name SLC39A6
Aliases Estrogen-regulated protein LIV-1, Solute carrier family 39 member 6, Zrt- and Irt-like protein 6, ZIP-6
Organism Homo sapiens (Human)
UniProt ID Q13433
Transmembrane Times 6
Length (aa) 755
Sequence MARKLSVILILTFALSVTNPLHELKAAAFPQTTEKISPNWESGINVDLAISTRQYHLQQLFYRYGENNSLSVEGFRKLLQNIGIDKIKRIHIHHDHDHHSDHEHHSDHERHSDHEHHSEHEHHSDHDHHSHHNHAASGKNKRKALCPDHDSDSSGKDPRNSQGKGAHRPEHASGRRNVKDSVSASEVTSTVYNTVSEGTHFLETIETPRPGKLFPKDVSSSTPPSVTSKSRVSRLAGRKTNESVSEPRKGFMYSRNTNENPQECFNASKLLTSHGMGIQVPLNATEFNYLCPAIINQIDARSCLIHTSEKKAEIPPKTYSLQIAWVGGFIAISIISFLSLLGVILVPLMNRVFFKFLLSFLVALAVGTLSGDAFLHLLPHSHASHHHSHSHEEPAMEMKRGPLFSHLSSQNIEESAYFDSTWKGLTALGGLYFMFLVEHVLTLIKQFKDKKKKNQKKPENDDDVEIKKQLSKYESQLSTNEEKVDTDDRTEGYLRADSQEPSHFDSQQPAVLEEEEVMIAHAHPQEVYNEYVPRGCKNKCHSHFHDTLGQSDDLIHHHHDYHHILHHHHHQNHHPHSHSQRYSREELKDAGVATLAWMVIMGDGLHNFSDGLAIGAAFTEGLSSGLSTSVAVFCHELPHELGDFAVLLKAGMTVKQAVLYNALSAMLAYLGMATGIFIGHYAENVSMWIFALTAGLFMYVALVDMVPEMLHNDASDHGCSRWGYFFLQNAGMLLGFGIMLLISIFEHKIVFRINF

Function of SLC39A6 Membrane Protein

Zinc is an important micronutrient desired for various cellular processes, such as DNA and protein synthesis, enzyme activity, as well as intracellular signaling. Distinguishingly, zinc plays a critical role in insulin-producing pancreatic islet β cells. Two major families of zinc transport proteins are supposed to regulate the intracellular zinc homeostasis, which are identified as the zinc efflux (ZnTs) transporter family and the Zrt- and Irt-like protein (ZIP) family. Generally, the ZIP family is responsible for zinc influx into the cytosol from extracellular sources and intracellular organelles. SLC39A6 is proved to promote nuclear translocation of the transcriptional factor Snail, the inducer of epithelial-mesenchymal transition (EMT), which is identified as a downstream target of the STAT3 pathway in the zebrafish gastrula organizer. SLC39A6 may function as a zinc-influx transporter, according to the structural similarity. Studies have shown that SLC39A6 is induced by the treatment of histone deacetylase inhibitors in tumor and plays a role in the apoptosis induction by histone deacetylase inhibitors. SLC39A6 is also regarded as a key mediator of breast cancer cell survival under high glucose conditions.

Predicted topologies of ZIP transporters. Fig.1 Predicted topologies of ZIP transporters. (Kambe, 2015)

Application of SLC39A6 Membrane Protein in Literature

  1. Matsui C., et al. Zinc and Its Transporter ZIP6 Are Key Mediators of Breast Cancer Cell Survival Under High Glucose Conditions. FEBS Lett. 2017, 591(20): 3348-3359. PubMed ID: 28833062

    The results of this study demonstrate that ZIP6 and ZIP10 are integral to cellular pathways and plasticity programmes, including EMT.

  2. Brethour D., et al. A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition. Sci Rep. 2017, 7: 40313. PubMed ID: 28098160

    Authors of this article attempt to investigate ZIP6 in an EMT (epithelial-to-mesenchymal transition) paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods.

  3. Taylor K.M., et al. Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. Biochem J. 2016, 473(16): 2531-44. PubMed ID: 27274087

    The results of this study indicate that decreased ZIP6 expression is tightly associated with resistance to hypoxia.

  4. Hennigar S.R., et al. Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review. Adv Nutr. 2016, 7(4): 735-746. PubMed ID: 27422508

    This study has determined the expression of sixteen zrt- and irt-like proteins, including ZIP6, and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion.

  5. Kong B.Y., et al. Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition. Mol Hum Reprod. 2014, 20(11): 1077-1089. PubMed ID: 25143461

    Results of this study reveal that ZIP6 and ZIP10 are enriched in the cortex, and labile zinc localizes to punctate cytoplasmic structures in the human oocyte.

SLC39A6 Preparation Options

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Reference

  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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