The reference OMIM entry for this protein is 300715

Magnesium transporter 1; magt1
Iap

DESCRIPTION

The magnesium ion, Mg(2+), is the most abundant divalent cation in mammalian cells and is an essential cofactor for ATP, nucleic acids, and numerous enzymes in plants and animals. MAGT1 is a highly selective transporter for Mg(2+) (summary by Li et al., 2011).

CLONING

Goytain and Quamme (2005) cloned mouse and human MAGT1. The deduced 335-amino acid human protein has a calculated molecular mass of 38 kD. MAGT1 contains 5 putative transmembrane domains, the first of which is likely cleaved. It has an N-glycosylation site in its first extracellular loop and several putative phosphorylation sites in its N-terminal region. Northern blot analysis detected variable Magt1 expression in all mouse tissues examined. Western blot analysis revealed a 38-kD Magt1 protein in all mouse tissues examined, as well as a 35-kD protein in some tissues. Using RT-PCR, Zhou and Clapham (2009) found that MAGT1 was expressed at nearly identical levels in all human tissues examined. Cell surface biotinylation and differential permeabilization experiments revealed that the N terminus of epitope-tagged MAGT1 was expressed at the cell surface of transfected HEK293 cells. Li et al. (2011) stated that the full-length MAGT1 protein contains 367 amino acids. It has an N-terminal signal peptide, followed by a large N-terminal segment, 4 transmembrane domains, and a small C-terminal tail.

GENE FUNCTION

Goytain and Quamme (2005) found that human MAGT1 mediated saturable Mg(2+) uptake when expressed in Xenopus oocytes. Transport was rheogenic, voltage dependent, and specific to Mg(2+), and it did not display time-dependent inactivation. Large external concentrations of Ni(2+), Zn(2+), and Mn(2+), but not Ca(2+) or Fe(2+), inhibited Mg(2+) transport in MAGT1-expressing oocytes. Real-time RT-PCR and Western blot analysis demonstrated that Magt1 mRNA and protein increased in mouse kidney epithelial cells cultured in low magnesium medium relative to normal medium and in kidney cortex of mice maintained on low magnesium diets compared with mice consuming normal diets. Zhou and Clapham (2009) showed that human MAGT1 and a TUSC3 (601385) isoform could complement yeast deficient in the Mg(2+) transporter Alr1. Knockdown of MAGT1 and/or TUSC3 lowered total and free intracellular Mg(2+) concentrations in human HEK293 and Jurkat cells. Zhou and Clapham (2009) hypothesized that MAGT1 and TUSC3 may function cooperatively in mediating cellular Mg(2+) uptake. Li et al. (2011) found that a rapid Mg(2+) influx was induced by antigen receptor stimulation in normal human T cells and by growth factor stimulation in nonlymphoid cells. Studies with cells from patients with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN; 300853), who have mutations in MAGT1 (see

MOLECULAR GENETICS

), showed that MAGT1 deficiency abrogated Mg(2+) influx, leading to impaired responses to antigen receptor engagement, including defective activation of PLCG1 (172420) and a markedly impaired Ca(2+) influx in T lymphocytes, but not B lymphocytes. Knockdown and reconstitution of MAGT1 in normal human T cells confirmed that MAGT1 was necessary and sufficient for the Mg(2+) influx required for optimal T-cell activation. Li et al. (2011) concluded that Mg(2+) has a role as an intracellular second messenger that couples cell surface receptor activation to intracellular effectors. MAGT1 is a critical regulator of basal i ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 300715 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).