Abstract
A growing body of evidence continues to demonstrate the vital roles that zinc and its transporters play on human health. The mammalian solute carrier 30 (SLC30) family, with ten current members, controls zinc efflux transport in cells. TMEM163, a recently reported zinc transporter, has similar characteristics in both predicted transmembrane domain structure and function to the cation diffusion facilitator (CDF) protein superfamily. This review discusses past and present data indicating that TMEM163 is a zinc binding protein that transports zinc in cells. We provide a brief background on TMEM163’s discovery, transport feature, protein interactome, and similarities, as well as differences, with known SLC30 (ZnT) protein family. We also examine recent reports that implicate TMEM163 directly or indirectly in various human diseases such as Parkinson’s disease, Mucolipidosis type IV and diabetes. Overall, the role of TMEM163 protein in zinc metabolism is beginning to be realized, and based on current evidence, we propose that it is likely a new CDF member belonging to mammalian SLC30 (ZnT) zinc efflux transporter proteins.
Highlights
Zinc is a micronutrient involved in many fundamental roles that are vital for routine bodily functions
The list listofofzinc zinctransporters transportersthat that appears correlated with various human disThe appears to to be be correlated with various human diseases eases the current is not exhaustive. It demonstrates thatplays zinc plays in the in current reviewreview is not exhaustive. It demonstrates that zinc many manyinroles in influencing and diseased states, and broadening the investiroles influencing normalnormal and diseased states, and broadening the investigation of gation of these proteins is of significant value to devise or discover a form of therapeutics these proteins is of significant value to devise or discover a form of therapeutics against against many debilitating in humans
The authors reported that a novel variant of Transmembrane 163 (TMEM163), believed to cause a partial loss of function, was found in 33% of study participants with T2D [61]. This TMEM163 variant was found to be associated with a high glycemic index and that fasting plasma insulin level is decreased among the participants (24 patients with T2D and 24 control subjects); the association was not found to be significant upon further analysis [61]
Summary
Zinc is a micronutrient involved in many fundamental roles that are vital for routine bodily functions. The widespread effects of and dependence on zinc by various proteins demonstrate the broad usefulness of this trace metal. Especially in humans, require zinc for proper immune responses. For some cell types, there is indication demonstrating that intracellular zinc accumulation leads to increased ROS formation in the mitochondria [9,10]. In diabetes mellitus (DM), there is evidence associating zinc imbalance occurring at the physiological and cellular levels [11,13]. While cases of zinc deficiency in human population are often more mild-to-moderate in their severity, it is relatively widespread and affects one in four people [3,11]. With zinc deficiency afflicting many people worldwide and a wide variety of health issues stemming from it, nutritional supplementation appears to be quite important. It is necessary to further understand zinc homeostasis with respect to the living cell
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