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SLC39A8 Membrane Protein Introduction

Introduction of SLC39A8

Zinc transporter ZIP8 (short for ZIP-8), alternatively known as BCG-induced integral membrane protein in monocyte clone 103 protein, or LIV-1 subfamily of ZIP zinc transporter 6 (LZT-Hs6), is encoded by the SLC39A8 gene in human. The zinc transporter SLC39A8 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). SLC39A8 is highly expressed in the pancreas. And SLC39A8 is also found in placenta, thymus, lung, pancreas, liver, and to a smaller extent, in spleen, heart, ovary, testis, colon, small intestine, leukocyte.

Basic Information of SLC39A8
Protein Name Zinc transporter ZIP8
Gene Name SLC39A8
Aliases BCG-induced integral membrane protein in monocyte clone 103 protein, Solute carrier family 39 member 8, Zrt- and Irt-like protein 8 (ZIP-8), LIV-1 subfamily of ZIP zinc transporter 6 (LZT-Hs6)
Organism Homo sapiens (Human)
UniProt ID Q13433
Transmembrane Times 8
Length (aa) 460
Sequence MAPGRAVAGLLLLAAAGLGGVAEGPGLAFSEDVLSVFGANLSLSAAQLQHLLEQMGAASRVGVPEPGQLHFNQCLTAEEIFSLHGFSNATQITSSKFSVICPAVLQQLNFHPCEDRPKHKTRPSHSEVWGYGFLSVTIINLASLLGLILTPLIKKSYFPKILTFFVGLAIGTLFSNAIFQLIPEAFGFDPKVDSYVEKAVAVFGGFYLLFFFERMLKMLLKTYGQNGHTHFGNDNFGPQEKTHQPKALPAINGVTCYANPAVTEANGHIHFDNVSVVSLQDGKKEPSSCTCLKGPKLSEIGTIAWMITLCDALHNFIDGLAIGASCTLSLLQGLSTSIAILCEEFPHELGDFVILLNAGMSTRQALLFNFLSACSCYVGLAFGILVGNNFAPNIIFALAGGMFLYISLADMFPEMNDMLREKVTGRKTDFTFFMIQNAGMLTGFTAILLITLYAGEIELE

Function of SLC39A8 Membrane Protein

Zinc transporter SLC39A8 is glycosylated and expressed in the mitochondria and plasma membrane, and it plays a role in the cellular import of zinc at the onset of inflammation. It also acts as a manganese and cadmium transporter. A study showed that SLC39A8 can also mediate the cellular uptake of iron, identifying it as the third mammalian transmembrane iron import protein. Aided by an intracellular zinc-selective fluorescent dye, it has been observed that CHO cells stably transfected with SLC39A8 accumulate and retain more zinc, as compared to other ZIP family members. SLC39A8 is also considered to be the main transporter of the toxic cation cadmium, which is found in cigarette smoke. The SLC39A8 protein shows high expression in T cells derived from human subjects and may provide a secondary level of IFN-gamma regulation in T cells, by control of zinc transport from the lysosome. Moreover, SLC39A8 is proved to contribute to the manganese reabsorption in the proximal tubule of the kidney and to the manganese uptake into the brain.

Subcellular localization of Zn transporters and MTs. Fig.1 Subcellular localization of Zn transporters and MTs. (Miao, 2013)

Application of SLC39A8 Membrane Protein in Literature

  1. Mei Z., et al. Knockdown of zinc transporter ZIP8 expression inhibits neuroblastoma progression and metastasis in vitro. Mol Med Rep. 2018, 18(1): 477-485. PubMed ID: 29749445

    This study suggests that Zip8 is a vital regulator of neuroblastoma cell proliferation and migration, indicating that Zip8 can be a potential therapeutic target for cancer and a promising diagnostic biomarker for human neuroblastoma.

  2. Pyle C.J., et al. Elemental Ingredients in the Macrophage Cocktail: Role of ZIP8 in Host Response to Mycobacterium tuberculosis. Int J Mol Sci. 2017, 18(11). PubMed ID: 29120360

    Authors of this article emphasize that the expression, localization, and function of ZIP8, which has important implications for TB prevention and dissemination.

  3. Riley L.G., et al. A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. J Inherit Metab Dis. 2017, 40(2): 261-269. PubMed ID: 27995398

    This study reported a novel SLC39A8 variant in siblings with features of the Leigh-like mitochondrial disease. Meanwhile, the results suggest SLC39A8 deficiency can cause both type II CDG and Leigh-like syndrome.

  4. Lin W., et al. Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. J Clin Invest. 2017, 127(6): 2407-2417. PubMed ID: 28481222

    The results of this study indicate that hepatic ZIP8 reclaims Mn from bile and regulates whole-body Mn homeostasis, and thus modulating the activity of Mn-dependent enzymes.

  5. Pyle C.J., et al. Zinc Modulates Endotoxin-Induced Human Macrophage Inflammation through ZIP8 Induction and C/EBPβ Inhibition. PLoS One. 2017, 12(1): e0169531. PubMed ID: 28056086

    Results of this study demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10.

SLC39A8 Preparation Options

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With advanced technology platforms and specialized expertise, Creative Biolabs can serve our clients with high-quality library screening services around the world. Our scientists are devoting to accelerate access to a comprehensive solution for membrane protein studies. Please feel free to contact us for more details.

Reference

  1. Miao X, et al. (2013). Zinc homeostasis in the metabolic syndrome and diabetes. Frontiers of medicine. 7(1), pp.31-52.

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