Reactome | SLC30A10 transports Mn2+ from cytosol to extracellular region

SLC30A10 transports Mn2+ from cytosol to extracellular region

Stable Identifier

R-HSA-8959798

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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SLC30A10 transports Mn2+ from cytosol to extracellular region

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Manganese (Mn2+) is an essential metal that functions as a cofactor required for the activity of numerous essential enzymes but at at elevated levels, M2+n becomes toxic as it enhances oxidative stress, compromises mitochondrial function and induces cell death. Mn2+ is excreted by the liver in bile but excess Mn2+ preferentially accumulates in the basal ganglia, leading to the development of an irreversible and incurable Parkinsonian-like syndrome (Tuschl et al. 2012, Quadri et al. 2012, Leyva-Illades et al. 2014). SLC30A10 had previously been presumed to be a zinc transporter but now has been confirmed to function as an essential Mn2+ transporter in humans (Tuschi et al. 2012), mediating the efflux of Mn2+ from cells ( Leyva-Illades et al. 2014) by antiporting calcium ions (Ca2+) into the cell (Levy et al., 2019).

Literature References

PubMed ID	Title	Journal	Year
25319704	SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity Leyva-Illades, D, Chen, P, Zogzas, CE, Hutchens, S, Mercado, JM, Swaim, CD, Morrisett, RA, Bowman, AB, Aschner, M, Mukhopadhyay, S	J. Neurosci.	2014
22341971	Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease Quadri, M, Federico, A, Zhao, T, Breedveld, GJ, Battisti, C, Delnooz, C, Severijnen, LA, Di Toro Mammarella, L, Mignarri, A, Monti, L, Sanna, A, Lu, P, Punzo, F, Cossu, G, Willemsen, R, Rasi, F, Oostra, BA, van de Warrenburg, BP, Bonifati, V	Am. J. Hum. Genet.	2012
30755481	Zinc transporter 10 (ZnT10)-dependent extrusion of cellular Mn²⁺ is driven by an active Ca²⁺-coupled exchange Levy, M, Elkoshi, N, Barber-Zucker, S, Hoch, E, Zarivach, R, Hershfinkel, M, Sekler, I	J Biol Chem	2019
22341972	Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man Tuschl, K, Clayton, PT, Gospe, SM, 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	Am. J. Hum. Genet.	2012