| Structural highlights
Disease
ZNT10_HUMAN Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
ZNT10_HUMAN Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange (PubMed:30755481). Required for intracellular manganese homeostasis, an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. Manganese can also be cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis (PubMed:22341972, PubMed:25319704, PubMed:26728129, PubMed:27226609, PubMed:27307044). Could also have an intracellular zinc ion transporter activity, directly regulating intracellular zinc ion homeostasis and more indirectly various signaling pathway and biological processes (PubMed:22427991, PubMed:26728129).[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Tuschl K, Clayton PT, Gospe SM Jr, Gulab S, Ibrahim S, Singhi P, Aulakh R, Ribeiro RT, Barsottini OG, Zaki MS, Del Rosario ML, Dyack S, Price V, Rideout A, Gordon K, Wevers RA, Chong WK, Mills PB. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet. 2012 Mar 9;90(3):457-66. PMID:22341972 doi:10.1016/j.ajhg.2012.01.018
- ↑ Patrushev N, Seidel-Rogol B, Salazar G. Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PLoS One. 2012;7(3):e33211. PMID:22427991 doi:10.1371/journal.pone.0033211
- ↑ Leyva-Illades D, Chen P, Zogzas CE, Hutchens S, Mercado JM, Swaim CD, Morrisett RA, Bowman AB, Aschner M, Mukhopadhyay S. SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. J Neurosci. 2014 Oct 15;34(42):14079-95. PMID:25319704 doi:10.1523/JNEUROSCI.2329-14.2014
- ↑ Zhao Y, Feresin RG, Falcon-Perez JM, Salazar G. Differential Targeting of SLC30A10/ZnT10 Heterodimers to Endolysosomal Compartments Modulates EGF-Induced MEK/ERK1/2 Activity. Traffic. 2016 Mar;17(3):267-88. PMID:26728129 doi:10.1111/tra.12371
- ↑ Nishito Y, Tsuji N, Fujishiro H, Takeda TA, Yamazaki T, Teranishi F, Okazaki F, Matsunaga A, Tuschl K, Rao R, Kono S, Miyajima H, Narita H, Himeno S, Kambe T. Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 Protein as a Manganese Transporter. J Biol Chem. 2016 Jul 8;291(28):14773-87. PMID:27226609 doi:10.1074/jbc.M116.728014
- ↑ Zogzas CE, Aschner M, Mukhopadhyay S. Structural Elements in the Transmembrane and Cytoplasmic Domains of the Metal Transporter SLC30A10 Are Required for Its Manganese Efflux Activity. J Biol Chem. 2016 Jul 29;291(31):15940-57. PMID:27307044 doi:10.1074/jbc.M116.726935
- ↑ Levy M, Elkoshi N, Barber-Zucker S, Hoch E, Zarivach R, Hershfinkel M, Sekler I. Zinc transporter 10 (ZnT10)-dependent extrusion of cellular Mn(2+) is driven by an active Ca(2+)-coupled exchange. J Biol Chem. 2019 Apr 12;294(15):5879-5889. PMID:30755481 doi:10.1074/jbc.RA118.006816
|
