Affinage

MMGT1

ER membrane protein complex subunit 5 · UniProt Q8N4V1

Round 2 corrected
Length
131 aa
Mass
14.7 kDa
Annotated
2026-04-28
36 papers in source corpus 2 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMGT1 (also designated ER membrane protein complex subunit 5) is a small, two-transmembrane-domain integral membrane protein that mediates saturable Mg²⁺ transport with a Km of ~1.5 mM, as demonstrated by reconstitution in Xenopus oocytes, and its transcript is upregulated under low-magnesium conditions in kidney epithelial cells (PMID:18057121). The protein localizes to the Golgi complex and post-Golgi vesicles, including early endosomes, where it occupies vesicular compartments distinct from its paralog MMgT2 (PMID:18057121). In macrophages, MMGT1 loss-of-function upregulates lipid metabolism genes and drives triacylglycerol-dependent lipid droplet accumulation via the orphan receptor GPR156, creating a metabolic environment that shifts Mycobacterium tuberculosis from active replication to a persistence state (PMID:37269834).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2007 High

    Identification of MMGT1 as a bona fide Mg²⁺ transporter resolved the molecular identity of an intracellular magnesium uptake pathway and established its kinetic parameters and transcriptional regulation by magnesium availability.

    Evidence Two-electrode voltage clamp and fluorescence-based Mg²⁺ uptake in Xenopus oocytes; RT-PCR of kidney epithelial cells under low-Mg conditions

    PMID:18057121

    Open questions at the time
    • No crystal or cryo-EM structure to define the ion permeation pathway
    • Physiological role of MMGT1-mediated Mg²⁺ transport in native tissues not established by knockout or knockdown
    • Selectivity for Mg²⁺ over other divalent cations not fully characterized
  2. 2007 Medium

    Localization of MMGT1 to the Golgi and post-Golgi vesicles (including early endosomes) established that this transporter operates in endomembrane compartments rather than at the plasma membrane, distinguishing it from classical surface Mg²⁺ channels.

    Evidence Immunofluorescence of HA-tagged MMGT1 in transfected COS-7 cells with organelle markers

    PMID:18057121

    Open questions at the time
    • Localization based on overexpressed tagged protein in a single cell line; endogenous localization not confirmed
    • Functional significance of Golgi/vesicular Mg²⁺ transport not tested
    • Whether MMGT1 also traffics to the ER (consistent with its EMC5 designation) was not examined
  3. 2023 High

    A genome-wide CRISPR screen in macrophages revealed that MMGT1 loss promotes Mycobacterium tuberculosis persistence by upregulating lipid metabolism and lipid droplet formation through a GPR156-dependent pathway, linking MMGT1 function to host innate immune control of intracellular pathogens.

    Evidence CRISPR screen in macrophages with multi-fluorescent Mtb reporter; MMGT1-KO macrophages; siRNA knockdown of GPR156; triacylglycerol synthesis inhibition; host transcriptomics

    PMID:37269834

    Open questions at the time
    • Whether the lipid-droplet phenotype is a direct consequence of impaired Mg²⁺ transport or an independent function of MMGT1 is unknown
    • Mechanism connecting MMGT1 to GPR156 signaling not defined
    • In vivo relevance of MMGT1-dependent Mtb persistence not tested in animal models

Open questions

Synthesis pass · forward-looking unresolved questions
  • The relationship between MMGT1's Mg²⁺ transport activity, its reported EMC5 identity as a subunit of the ER membrane protein complex, and its role in lipid metabolism/pathogen persistence remains unresolved.
  • No study has tested whether MMGT1 functions as part of the EMC in the context of membrane protein insertion
  • Structural basis of MMGT1 ion transport and potential dual functionality is entirely unknown
  • Whether Mg²⁺ homeostasis mechanistically links to the lipid-droplet accumulation phenotype has not been examined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 1
Localization
GO:0005768 endosome 1 GO:0005794 Golgi apparatus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
GO:0005215 transporter activity 1 R-HSA-1430728 Metabolism 1 R-HSA-168256 Immune System 1 R-HSA-382551 Transport of small molecules 1
Partners
GPR156

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 MMgT1 (MMGT1) is a small integral membrane protein of 131 amino acids with two predicted transmembrane domains that mediates saturable Mg2+ transport when expressed in Xenopus laevis oocytes, with a Michaelis constant of 1.47 ± 0.17 mM. Its mRNA is upregulated approximately threefold in kidney epithelial cells and kidney cortex under low-magnesium conditions. Two-electrode voltage-clamp analysis and fluorescence measurements in Xenopus oocytes; real-time RT-PCR; Michaelis-Menten kinetic analysis American journal of physiology. Cell physiology High 18057121
2007 MMgT1 protein localizes to the Golgi complex and post-Golgi vesicles, including early endosomes, in COS-7 cells expressing HA-tagged MMgT1. MMgT1 and MMgT2 are found in separate populations of post-Golgi vesicles, suggesting distinct vesicular trafficking pathways for each transporter. Immunohistochemistry with HA-tagged fusion protein in transfected COS-7 cells; subcellular fractionation American journal of physiology. Cell physiology Medium 18057121
2023 MMGT1 loss-of-function in macrophages promotes a switch of Mycobacterium tuberculosis from active replication to a persistence state. MMGT1-deficient macrophages upregulate lipid metabolism genes and accumulate lipid droplets during Mtb infection; targeting triacylglycerol synthesis reduces both lipid droplet formation and Mtb persistence. The orphan G protein-coupled receptor GPR156 is identified as a key inducer of lipid droplet accumulation downstream of MMGT1 loss. Genome-wide CRISPR screen; MMGT1-knockout macrophages; multi-fluorescent Mtb reporter strain; siRNA knockdown; triacylglycerol synthesis inhibition; host transcriptome analysis of infected macrophages Cell host & microbe High 37269834

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2011 Defining human ERAD networks through an integrative mapping strategy. Nature cell biology 427 22119785
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2017 The ER membrane protein complex is a transmembrane domain insertase. Science (New York, N.Y.) 233 29242231
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2018 EMC Is Required to Initiate Accurate Membrane Protein Topogenesis. Cell 190 30415835
2018 The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins. eLife 170 29809151
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2020 Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation. Cells 146 32344865
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2020 Structural basis for membrane insertion by the human ER membrane protein complex. Science (New York, N.Y.) 137 32439656
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2021 Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 113 34349018
2020 Structure of the ER membrane complex, a transmembrane-domain insertase. Nature 108 32494008
2007 Identification and characterization of a novel family of membrane magnesium transporters, MMgT1 and MMgT2. American journal of physiology. Cell physiology 43 18057121
2020 Magnesium Supplementation Attenuates Pulmonary Hypertension via Regulation of Magnesium Transporters. Hypertension (Dallas, Tex. : 1979) 39 33356397
1994 Generation and characterization of mouse microglial cell lines. Journal of neuroimmunology 36 8034755
2019 ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice. Cell death and differentiation 31 31263175
2023 Identification of host regulators of Mycobacterium tuberculosis phenotypes uncovers a role for the MMGT1-GPR156 lipid droplet axis in persistence. Cell host & microbe 10 37269834