1.A.76 The Magnesium Transporter1 (MagT1) Family 

Intracellular magnesium is abundant, highly regulated and plays an important role in biochemical functions. Unique mammalian Mg2+ transporters have been biochemically identified. Goytain and Quamme 2005 identified a Mg2+ transporter encoded by an implantation-associated protein precursor, IAP, that is regulated by magnesium. They designated this protein, MagT1. MagT1 is of 335 amino acids and possesses five TMSs with an N-terminal cleavage site and a number of phosphorylation sites. When expressed in Xenopus laevis oocytes, MagT1 mediates saturable Mg2+ uptake with a Michaelis constant of 0.23 mM. Transport of Mg2+ by MagT1 is rheogenic, voltage-dependent, and does not display time-dependent inactivation. Transport is specific to Mg2+ as other divalent cations do not evoke currents. Large external concentrations of some cations inhibited Mg2+ transport (Ni2+, Zn2+, Mn2+) in MagT1-expressing oocytes although Ca2+and Fe2+ were without effect (Goytain and Quamme 2005).  MagT1 has an N-terminal thioredoxin domain (Trx family) of unknown function.


MagT1 and its homologues are called tumor suppressor candidate 3 genes and oligosaccharidyl transferase. They are found in various eukaryotes (animals, plants, fungi etc.).
The identification of genetic changes and their functional consequences in patients with immunodeficiency revealed that magnesium and MAGT1 are key molecular players for T cell-mediated immune responses (Trapani et al. 2015). This led to the description of XMEN (X-linked immunodeficiency with magnesium defect, Epstein Barr Virus infection, and neoplasia) syndrome, for which Mg2+ supplementation has been shown to be beneficial. Similarly, the identification of a copy-number variation (CNV) leading to dysfunctional MAGT1 in a family with atypical ATRX syndrome and skin abnormalities, suggested that the MAGT1 defect is responsible for the cutaneous problems. Recent genetic investigations questioned the previously proposed role for MAGT1 in intellectual disability (Trapani et al. 2015). Expression levels of MAGT1 may be biomarkers for the diagnosis and prognosis of several types of cancer (Molee et al. 2015).
 

Zhou and Clapham 2009 identified two mammalian genes, MagT1 and TUSC3, catalyzing Mg2+ influx. MagT1 is universally expressed in all human tissues, and its expression level is up-regulated in low extracellular Mg2+. Knockdown of either MagT1 or TUSC3 protein lowered the total and free intracellular Mg2+ concentrations in mammalian cell lines. Morpholino knockdown of MagT1 and TUSC3 protein expression in zebrafish embryos resulted in early developmental arrest; excess Mg2+ or supplementation with mammalian mRNAs rescued these effects. Thus, MagT1 and TUSC3 are vertebrate plasma membrane Mg2+ transport system (Zhou and Clapham 2009).

The reaction catalyzed by MagT1 is:

Mg2+ (out) → Mg 2+ (in)



This family belongs to the .

 

References:

Goytain, A. and G.A. Quamme. (2005). Identification and characterization of a novel mammalian Mg2+ transporter with channel-like properties. BMC Genomics 6: 48.

Molee, P., P. Adisakwattana, O. Reamtong, S. Petmitr, T. Sricharunrat, N. Suwandittakul, and U. Chaisri. (2015). Up-regulation of AKAP13 and MAGT1 on cytoplasmic membrane in progressive hepatocellular carcinoma: a novel target for prognosis. Int J Clin Exp Pathol 8: 9796-9811.

Trapani, V., N. Shomer, and E. Rajcan-Separovic. (2015). The role of MAGT1 in genetic syndromes. Magnes Res 28: 46-55.

Wild, R., J. Kowal, J. Eyring, E.M. Ngwa, M. Aebi, and K.P. Locher. (2018). Structure of the yeast oligosaccharyltransferase complex gives insight into eukaryotic N-glycosylation. Science 359: 545-550.

Zhou, H. and D.E. Clapham. (2009). Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development. Proc. Natl. Acad. Sci. USA 106: 15750-15755.

Examples:

TC#NameOrganismal TypeExample
1.A.76.1.1

Magnesium transporter, MagT1 (Goytain and Quamme, 2005; Schmitz et al., 2007; Zhou and Clapham, 2009).  As of 2018, the function of this protein as a Mg2+ transporter was under debate (Schäffers et al. 2018).

Eukaryotes

MagT1 of Homo sapiens (Q9H0U3)

 
1.A.76.1.10

Ost3/Ost6 homologue of 334 aas and 5 TMSs

Ost3-like protein of Chlamydomonas reinhardtii (Chlamydomonas smithii)

 
1.A.76.1.11

Uncharacterized protein of 277 aas

UP of Reticulomyxa filosa

 
1.A.76.1.12

Uncharacterized protein of 362 aas

UP of Naegleria gruberi (Amoeba)

 
1.A.76.1.13

Uncharacterized protein of 328 aas and 7 (or 5) TMSs

UP of Tetrapisispora blattae (Yeast) (Kluyveromyces blattae)

 
1.A.76.1.14

Mg2+ transporter, MagT1 homologue of 331 aas

MagT1 homologue of Pyronema omphalodes

 
1.A.76.1.2

Mg2+ transporter; also called Tumor suppressor candidate 3 isoform a, Tusc3a (69% identity with MagT1) (Zhou and Clapham, 2009).

Animals

Tusc3a of Homo sapiens (Q13454)

 
1.A.76.1.3

Magnesium transporter protein 1 (MagT1) with a thioredoxin domain (residues 50 - 150) and an Ost3/Ost6 domain (residues 160 - 310 with 4 TMSs).

Animals

MagT1 of Danio rerio

 
1.A.76.1.4

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 3

Amoeba

Ost3 of Dictyostelium discoideum

 
1.A.76.1.5

Ubiquitin conjugating enzyme of 345 aas with 4 C-terminal TMSs

Alveolata

Ubiquitin conjugating enzyme of Oxytricha trifallax

 
1.A.76.1.7

Putative magnesium transport protein of 354 aas and 4 C-terminal TMSs.

MagT1 homologue of Albugo laibachii

 
1.A.76.1.8

Glycosyl transferase, Ost3 of 350 aas and 4 TMSs.  This protein is a subunit of the yeast oligosaccharyltransferase complex involved in N-glycosylation (Wild et al. 2018). It is not the catalytic subunit (see TC# 9.B.142.3.14).

Ost3 of Saccharomyces cerevisiae

 
1.A.76.1.9

Ost6-like protein of 332 aas and 4 TMSs.

Ost6 of Saccharomyces cerevisiae (Baker's yeast)

 
Examples:

TC#NameOrganismal TypeExample
1.A.76.2.1

Oligosaccharyltransferase complex/magnesium transporter family protein of 173 aas and 3 or 4 TMSs. The proteins in this family are part of a complex of eight ER proteins that transfers core oligosaccharide from dolichol carrier to Asn-X-Ser/Thr motifs. This family includes both OST3 and OST6, each of which contains four predicted transmembrane helices. Disruption of OST3 and OST6 leads to a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation.

Plants

Uncharacterized protein of Arabidopsis thaliana (Mouse-ear cress)

 
1.A.76.2.2

Uncharacterized protein of 148 aas and 3 TMSs

Diplomonadida

UP of Giardia intestinalis (Giardia lamblia)

 
1.A.76.2.3

Uncharacterized protein of 159 aas and 3 TMSs

Rhodophyta

UP of Cyanidioschyzon merolae

 
1.A.76.2.4

Uncharacterized protein of 433 aas with 3 N-terminal TMSs.

UP of Dictyostelium discoideum (Slime mold)

 
1.A.76.2.5

Oligosaccharyl transferase complex subunit, EgrG of 144 aas and 3 TMSs.

OST3 family member of Echinococcus granulosus (Hydatid tapeworm)

 
1.A.76.2.6

OST3/OST6 superfamily protein of 158 aas and 3 TMSs.

OST3 family protein of 158 aas

 
1.A.76.2.7

OST3/OST6 Family protein of 159 aas and 3 TMSs.

OST3 homologue of Trichomonas vaginalis

 
1.A.76.2.8

Oligosaccharidyl transferase DS2 of 173 aas and 4 TMSs

DS2 of Loa loa (Eye worm) (Filaria loa)