Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity. Transports an electroneutral complex composed of a divalent metal cation and two bicarbonate anions or alternatively a bicarbonate and a selenite anion. Thereby, it also contributes to the cellular uptake of selenium, an essential trace metal and micronutrient. Also imports cadmium a non-essential metal which is cytotoxic and carcinogenic. May also transport iron and cobalt through membranes. Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development. Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization. Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes. Protects, for instance, cells from injury and death at the onset of inflammation. By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries. Reclaims manganese from the bile at the apical membrane of hepatocytes, thereby regulating the activity of the manganese-dependent enzymes through the systemic levels of the nutrient.
Background References
1. Choi E.K., Nguyen T.T., Gupta N., Iwase S., Seo Y.A. Functional analysis of SLC39A8 mutations and their implications for manganese deficiency and mitochondrial disorders. Sci. Rep. 8:3163-3163 (2018).
2. Wang C.Y., Jenkitkasemwong S., Duarte S., Sparkman B.K., Shawki A., Mackenzie B., Knutson M.D. ZIP8 is an iron and zinc transporter whose cell-surface expression is up- regulated by cellular iron loading. J. Biol. Chem. 287:34032-34043 (2012).
Western blot analysis of SLC39A8 on different lysates with Mouse anti-SLC39A8 antibody (HA601161) at 1/1,000 dilution.
Lane 1: Jurkat cell lysate Lane 2: SiHa cell lysate Lane 3: HeLa cell lysate
Lysates/proteins at 30 µg/Lane.
Predicted band size: 50 kDa Observed band size: 65 kDa
Exposure time: 1 minute;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (HA601161) at 1/1,000 dilution was used in 5% NFDM/TBST at room temperature for 2 hours. Goat Anti-Mouse IgG - HRP Secondary Antibody (HA1006) at 1:100,000 dilution was used for 1 hour at room temperature.
Western blot analysis of SLC39A8 on different lysates with Mouse anti-SLC39A8 antibody (HA601161) at 1/1,000 dilution.
Lane 1: HUVEC cell lysate (30 µg/Lane) Lane 2: NIH/3T3 cell lysate (30 µg/Lane) Lane 3: RAW264.7 cell lysate (20 µg/Lane) Lane 4: PC-12 cell lysate (26 µg/Lane)
Predicted band size: 50 kDa Observed band size: 65/130 kDa
Exposure time: 1 minute;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (HA601161) at 1/1,000 dilution was used in 5% NFDM/TBST at room temperature for 2 hours. Goat Anti-Mouse IgG - HRP Secondary Antibody (HA1006) at 1:100,000 dilution was used for 1 hour at room temperature.
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