Alternative titles; symbols
HGNC Approved Gene Symbol: MMGT1
Cytogenetic location: Xq26.3 Genomic coordinates (GRCh38): X:135,960,588-135,973,988 (from NCBI)
MMGT1 is a Golgi-resident magnesium transporter (Goytain and Quamme, 2008). MMGT1 is also a subunit of the endoplasmic reticulum (ER) membrane protein complex (EMC), which is required for accurate membrane protein topogenesis (Chitwood et al., 2018).
By database analysis, Goytain and Quamme (2008) identified mouse Mmgt1 as a 131-amino acid protein with 2 putative transmembrane domains. MMGT1 is highly conserved among human, mouse, rat, and pig, with mouse Mmgt1 sharing 97% and 80% amino acid similarity with human MMGT1 and mouse Mmgt2, respectively. Real-time RT-PCR detected abundant Mmgt1 expression in mouse heart muscle and kidney, with lower expression in liver and brain, and little expression in intestine and colon. Immunofluorescence assays showed that HA-tagged Mmgt1 localized predominately in Golgi of transfected COS-7 cells, with appreciable amounts in post-Golgi vesicles and early recycling endosomes.
Goytain and Quamme (2008) stated that the MMGT1 gene maps to human chromosome Xq26.3 and to mouse chromosome XA5.
By microarray analysis, Goytain and Quamme (2008) identified Mmgt1 as a magnesium-responsive gene, as Mmgt1 expression was upregulated in kidney cortex of hypomagnesemic mice in response to magnesium deficiency and in mouse distal convoluted tubule (MDCT) cells cultured in low magnesium. Further analysis demonstrated that Mmgt1 mediated Mg(2+) transport, as expressed Mmgt1 localized in surface membranes of Xenopus oocytes and increased uptake of Mg(2+) by the oocytes.
By manipulating the human EMC5 and EMC6 (620261) subunits of the EMC, Chitwood et al. (2018) showed that EMC was required for posttranslational stability of the G protein-coupled receptor (GPCR) beta-1-adrenergic receptor (ADRB1; 109630), as the absence of EMC led to elevated degradation of ADRB1. In vitro reconstitution of ADRB1 revealed that EMC was required for accurate topogenesis of the first transmembrane domain (TMD1) of ADRB1, as well as most GPCRs, because without EMC, correct topology and membrane insertion of TMD1 failed for the receptors. For transmembrane proteins with N-terminal translocation to the exoplasmic side of the ER membrane (Nexo), the SEC61 complex (see 609213) is required for Nexo signal anchor insertion into the membrane. However, GPCR TMD1 insertion into membranes could occur without the SEC61 complex, and the EMC was sufficient for Nexo signal anchor insertion after the protein was targeted to the ER. Instead, the SEC61 complex was required for insertion of subsequent transmembrane domains, but EMC was not required for insertion, folding, or maturation steps beyond TMD1 insertion.
By knockdown of EMC subunits, including Emc5, Gaspar et al. (2022) demonstrated that the EMC was required for male fertility in Drosophila, as EMC deficiency resulted in reduced sperm production. Further analysis of Drosophila with Emc5 knockdown revealed that EMC was required for sperm differentiation.
Chitwood, P. J., Juszkiewicz, S., Guna, A., Shao, S., Hegde, R. S. EMC is required to initiate accurate membrane protein topogenesis. Cell 175: 1507-1519, 2018. [PubMed: 30415835] [Full Text: https://doi.org/10.1016/j.cell.2018.10.009]
Gaspar, C. J., Vieira, L. C., Santos, C. C., Christianson, J. C., Jakubec, D., Strisovsky, K., Adrain, C., Domingos, P. M. EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel. EMBO Rep. 23: e53210, 2022. [PubMed: 34918864] [Full Text: https://doi.org/10.15252/embr.202153210]
Goytain, A., Quamme, G. A. Identification and characterization of a novel family of membrane magnesium transporters, MMgT1 and MMgT2. Am. J. Physiol. Cell Physiol. 294: C495-C502, 2008. [PubMed: 18057121] [Full Text: https://doi.org/10.1152/ajpcell.00238.2007]