{"gene":"MMGT1","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2007,"finding":"MMgT1 (MMGT1) mediates saturable Mg2+ transport when expressed in Xenopus laevis oocytes, with a Michaelis constant of 1.47 ± 0.17 mM, as measured by two-electrode voltage-clamp analysis and fluorescence measurements.","method":"Heterologous expression in Xenopus oocytes; two-electrode voltage-clamp electrophysiology; fluorescence Mg2+ measurements","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro transport assay with two orthogonal methods (electrophysiology + fluorescence) in a single study, not independently replicated","pmids":["18057121"],"is_preprint":false},{"year":2007,"finding":"MMgT1 protein localizes to the Golgi complex and post-Golgi vesicles, including early endosomes, in COS-7 cells expressing MMgT1-HA fusion protein, and this localization increases upon low-magnesium conditions in parallel with increased transcript and protein levels.","method":"Immunohistochemistry of HA-tagged MMgT1 in transfected COS-7 cells; real-time RT-PCR; subcellular fractionation/immunostaining","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single immunohistochemistry-based localization study with tagged overexpressed protein","pmids":["18057121"],"is_preprint":false},{"year":2020,"finding":"The yeast ortholog Emc5 (corresponding to human MMGT1/EMC5) forms part of the transmembrane region of the ER membrane complex (EMC), contributing to a five-TMH fold centred around Emc3 that resembles the prokaryotic YidC insertase and delineates a hydrophilic client protein pocket required for transmembrane helix insertion.","method":"Cryo-electron microscopy structure of the S. cerevisiae EMC; mutational studies validating functional role of the transmembrane architecture","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure at atomic detail combined with mutagenesis validating functional importance, published in a high-rigor study","pmids":["32494008"],"is_preprint":false},{"year":2019,"finding":"Loss-of-function of emc5 (Drosophila ortholog of MMGT1/EMC5) results in defective phototransduction, photoreceptor cell degeneration, and reduced rhodopsin levels, demonstrating that EMC5 is required for rhodopsin biosynthesis independent of the ERAD pathway.","method":"Genome-wide genetic screen in Drosophila; loss-of-function allele isolation; functional phototransduction assays; epistasis with ERAD pathway mutants","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function in an in vivo model with defined cellular phenotype and pathway placement (ERAD-independent), validated in Drosophila with null alleles","pmids":["31263175"],"is_preprint":false},{"year":2023,"finding":"MMGT1 deficiency in macrophages promotes Mycobacterium tuberculosis persistence by upregulating lipid metabolism genes and accumulating lipid droplets; the orphan GPCR GPR156 is identified as a key downstream inducer of lipid droplet accumulation in MMGT1-deficient cells, and targeting triacylglycerol synthesis reduces both droplet formation and Mtb persistence.","method":"Genome-wide CRISPR screen; MMGT1 knockout macrophages; transcriptomic analysis; lipid droplet quantification; siRNA/inhibitor targeting triacylglycerol synthesis; phenotype-specific validation of GPR156 as epistatic effector","journal":"Cell host & microbe","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide CRISPR screen hit validated with KO macrophages, multiple orthogonal methods (transcriptomics, lipid droplet imaging, pharmacological rescue), and epistasis via GPR156 in a single rigorous study","pmids":["37269834"],"is_preprint":false}],"current_model":"MMGT1 (EMC5/TMEM32) is a two-transmembrane-domain subunit of the ER membrane complex (EMC) that contributes to a hydrophilic client-protein pocket structurally homologous to prokaryotic YidC insertases and is required for co-translational insertion of transmembrane helices and biosynthesis of multi-pass membrane proteins such as rhodopsin; independently, when present in Golgi/post-Golgi compartments of epithelial cells it mediates saturable Mg2+ transport, and in macrophages it suppresses lipid droplet accumulation via the GPR156 signaling axis to restrict Mycobacterium tuberculosis persistence."},"narrative":{"mechanistic_narrative":"MMGT1 (EMC5/EMC5) is a two-transmembrane subunit of the ER membrane complex (EMC) that supports the co-translational biogenesis of multi-pass membrane proteins [PMID:32494008, PMID:31263175]. Within the EMC, the yeast ortholog Emc5 contributes to a five-transmembrane-helix fold centered on Emc3 that structurally resembles the prokaryotic YidC insertase and shapes a hydrophilic client-protein pocket required for transmembrane helix insertion [PMID:32494008]. Consistent with an insertase role, loss of the Drosophila ortholog impairs rhodopsin biosynthesis and causes photoreceptor degeneration independent of the ERAD pathway [PMID:31263175]. Independent of its EMC function, MMGT1 mediates saturable Mg2+ transport when heterologously expressed, with localization to the Golgi and post-Golgi/endosomal compartments that increases under low-magnesium conditions [PMID:18057121]. In macrophages, MMGT1 restricts lipid droplet accumulation through the orphan GPCR GPR156 axis, and its loss promotes Mycobacterium tuberculosis persistence via upregulated triacylglycerol synthesis [PMID:37269834].","teleology":[{"year":2007,"claim":"Established a first molecular function for MMGT1 by showing it can move Mg2+ across membranes, framing it as a candidate magnesium transporter.","evidence":"Heterologous expression in Xenopus oocytes with two-electrode voltage-clamp electrophysiology and fluorescence Mg2+ measurements","pmids":["18057121"],"confidence":"Medium","gaps":["Single study, not independently replicated","Transport mechanism (channel vs carrier) and physiological substrate range unresolved","Does not reconcile transport activity with later EMC subunit role"]},{"year":2007,"claim":"Placed the protein in the secretory pathway by mapping its localization to Golgi and post-Golgi vesicles and linking abundance to magnesium availability.","evidence":"Immunohistochemistry of HA-tagged MMgT1 in transfected COS-7 cells with real-time RT-PCR and fractionation","pmids":["18057121"],"confidence":"Medium","gaps":["Relies on overexpressed tagged protein in a single lab","Does not establish endogenous localization or ER-resident EMC pool","Mechanism linking low Mg2+ to increased expression unknown"]},{"year":2019,"claim":"Demonstrated an in vivo requirement of the EMC5 ortholog for membrane protein biogenesis, showing rhodopsin synthesis depends on it independent of ERAD.","evidence":"Genome-wide genetic screen and loss-of-function alleles in Drosophila with phototransduction assays and ERAD epistasis","pmids":["31263175"],"confidence":"High","gaps":["Client repertoire beyond rhodopsin not defined","Molecular step (insertion vs folding vs stability) not resolved in this system"]},{"year":2020,"claim":"Resolved the structural basis of EMC5 function, showing it forms part of a YidC-like transmembrane insertase architecture that creates a client pocket for TMH insertion.","evidence":"Cryo-EM structure of S. cerevisiae EMC with validating mutagenesis","pmids":["32494008"],"confidence":"High","gaps":["Structure is of the yeast complex; human MMGT1-specific contacts inferred","Does not address the reported Golgi Mg2+ transport activity","Dynamics of client engagement not captured"]},{"year":2023,"claim":"Connected MMGT1 to host defense, showing it suppresses macrophage lipid droplet accumulation through GPR156 to limit M. tuberculosis persistence.","evidence":"Genome-wide CRISPR screen, MMGT1-knockout macrophages, transcriptomics, lipid droplet imaging, and pharmacological targeting of triacylglycerol synthesis","pmids":["37269834"],"confidence":"High","gaps":["Mechanistic link between MMGT1 loss and GPR156 induction not defined","Whether the phenotype derives from EMC insertase function or Mg2+ transport is unresolved"]},{"year":null,"claim":"It remains unresolved how MMGT1's role as an EMC insertase subunit relates mechanistically to its reported Golgi/post-Golgi Mg2+ transport activity and its macrophage lipid-droplet phenotype.","evidence":"No single study integrates the insertase, transport, and immunometabolic activities","pmids":[],"confidence":"Medium","gaps":["No reconciliation of ER EMC localization with Golgi Mg2+ transport","Human structure and direct client list not established","Whether Mg2+ transport is an intrinsic activity or indirect remains open"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,3]}],"complexes":["ER membrane complex (EMC)"],"partners":["EMC3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N4V1","full_name":"ER membrane protein complex subunit 5","aliases":["Membrane magnesium transporter 1","Transmembrane protein 32"],"length_aa":131,"mass_kda":14.7,"function":"Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:29242231, PubMed:29809151, PubMed:30415835, PubMed:32439656, PubMed:32459176). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:29242231, PubMed:29809151, PubMed:30415835). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:29809151, PubMed:30415835). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (By similarity). May be involved in Mg(2+) transport (By similarity)","subcellular_location":"Endoplasmic reticulum membrane; Golgi apparatus membrane; Early endosome membrane","url":"https://www.uniprot.org/uniprotkb/Q8N4V1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MMGT1","classification":"Not Classified","n_dependent_lines":500,"n_total_lines":1208,"dependency_fraction":0.4139072847682119},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000169446","cell_line_id":"CID001519","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"EMC2","stoichiometry":0.2},{"gene":"EMC4","stoichiometry":0.2},{"gene":"EMC7","stoichiometry":0.2},{"gene":"EMC1","stoichiometry":0.2},{"gene":"LBR","stoichiometry":0.2},{"gene":"EMC3","stoichiometry":0.2},{"gene":"CCDC47","stoichiometry":0.2},{"gene":"NDUFA3","stoichiometry":0.2},{"gene":"TMEM33","stoichiometry":0.2},{"gene":"GCSH","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001519","total_profiled":1310},"omim":[{"mim_id":"620273","title":"ENDOPLASMIC RETICULUM MEMBRANE PROTEIN COMPLEX, SUBUNIT 3; EMC3","url":"https://www.omim.org/entry/620273"},{"mim_id":"620261","title":"ENDOPLASMIC RETICULUM MEMBRANE PROTEIN COMPLEX, SUBUNIT 6; EMC6","url":"https://www.omim.org/entry/620261"},{"mim_id":"301098","title":"MEMBRANE MAGNESIUM TRANSPORTER 1; MMGT1","url":"https://www.omim.org/entry/301098"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MMGT1"},"hgnc":{"alias_symbol":["EMC5"],"prev_symbol":["TMEM32"]},"alphafold":{"accession":"Q8N4V1","domains":[{"cath_id":"1.10.287","chopping":"2-67","consensus_level":"medium","plddt":91.6438,"start":2,"end":67}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N4V1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N4V1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N4V1-F1-predicted_aligned_error_v6.png","plddt_mean":79.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MMGT1","jax_strain_url":"https://www.jax.org/strain/search?query=MMGT1"},"sequence":{"accession":"Q8N4V1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N4V1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N4V1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N4V1"}},"corpus_meta":[{"pmid":"32494008","id":"PMC_32494008","title":"Structure of the ER membrane complex, a transmembrane-domain insertase.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32494008","citation_count":110,"is_preprint":false},{"pmid":"18057121","id":"PMC_18057121","title":"Identification and characterization of a novel family of membrane magnesium transporters, MMgT1 and MMgT2.","date":"2007","source":"American journal of physiology. Cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/18057121","citation_count":43,"is_preprint":false},{"pmid":"33356397","id":"PMC_33356397","title":"Magnesium Supplementation Attenuates Pulmonary Hypertension via Regulation of Magnesium Transporters.","date":"2020","source":"Hypertension (Dallas, Tex. : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/33356397","citation_count":40,"is_preprint":false},{"pmid":"8034755","id":"PMC_8034755","title":"Generation and characterization of mouse microglial cell lines.","date":"1994","source":"Journal of neuroimmunology","url":"https://pubmed.ncbi.nlm.nih.gov/8034755","citation_count":36,"is_preprint":false},{"pmid":"31263175","id":"PMC_31263175","title":"ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice.","date":"2019","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/31263175","citation_count":31,"is_preprint":false},{"pmid":"37269834","id":"PMC_37269834","title":"Identification of host regulators of Mycobacterium tuberculosis phenotypes uncovers a role for the MMGT1-GPR156 lipid droplet axis in persistence.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/37269834","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5135,"output_tokens":1408,"usd":0.018263,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8095,"output_tokens":2184,"usd":0.047538,"stage2_stop_reason":"end_turn"},"total_usd":0.065801,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"MMgT1 (MMGT1) mediates saturable Mg2+ transport when expressed in Xenopus laevis oocytes, with a Michaelis constant of 1.47 ± 0.17 mM, as measured by two-electrode voltage-clamp analysis and fluorescence measurements.\",\n      \"method\": \"Heterologous expression in Xenopus oocytes; two-electrode voltage-clamp electrophysiology; fluorescence Mg2+ measurements\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro transport assay with two orthogonal methods (electrophysiology + fluorescence) in a single study, not independently replicated\",\n      \"pmids\": [\"18057121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"MMgT1 protein localizes to the Golgi complex and post-Golgi vesicles, including early endosomes, in COS-7 cells expressing MMgT1-HA fusion protein, and this localization increases upon low-magnesium conditions in parallel with increased transcript and protein levels.\",\n      \"method\": \"Immunohistochemistry of HA-tagged MMgT1 in transfected COS-7 cells; real-time RT-PCR; subcellular fractionation/immunostaining\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single immunohistochemistry-based localization study with tagged overexpressed protein\",\n      \"pmids\": [\"18057121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The yeast ortholog Emc5 (corresponding to human MMGT1/EMC5) forms part of the transmembrane region of the ER membrane complex (EMC), contributing to a five-TMH fold centred around Emc3 that resembles the prokaryotic YidC insertase and delineates a hydrophilic client protein pocket required for transmembrane helix insertion.\",\n      \"method\": \"Cryo-electron microscopy structure of the S. cerevisiae EMC; mutational studies validating functional role of the transmembrane architecture\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure at atomic detail combined with mutagenesis validating functional importance, published in a high-rigor study\",\n      \"pmids\": [\"32494008\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Loss-of-function of emc5 (Drosophila ortholog of MMGT1/EMC5) results in defective phototransduction, photoreceptor cell degeneration, and reduced rhodopsin levels, demonstrating that EMC5 is required for rhodopsin biosynthesis independent of the ERAD pathway.\",\n      \"method\": \"Genome-wide genetic screen in Drosophila; loss-of-function allele isolation; functional phototransduction assays; epistasis with ERAD pathway mutants\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function in an in vivo model with defined cellular phenotype and pathway placement (ERAD-independent), validated in Drosophila with null alleles\",\n      \"pmids\": [\"31263175\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MMGT1 deficiency in macrophages promotes Mycobacterium tuberculosis persistence by upregulating lipid metabolism genes and accumulating lipid droplets; the orphan GPCR GPR156 is identified as a key downstream inducer of lipid droplet accumulation in MMGT1-deficient cells, and targeting triacylglycerol synthesis reduces both droplet formation and Mtb persistence.\",\n      \"method\": \"Genome-wide CRISPR screen; MMGT1 knockout macrophages; transcriptomic analysis; lipid droplet quantification; siRNA/inhibitor targeting triacylglycerol synthesis; phenotype-specific validation of GPR156 as epistatic effector\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide CRISPR screen hit validated with KO macrophages, multiple orthogonal methods (transcriptomics, lipid droplet imaging, pharmacological rescue), and epistasis via GPR156 in a single rigorous study\",\n      \"pmids\": [\"37269834\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MMGT1 (EMC5/TMEM32) is a two-transmembrane-domain subunit of the ER membrane complex (EMC) that contributes to a hydrophilic client-protein pocket structurally homologous to prokaryotic YidC insertases and is required for co-translational insertion of transmembrane helices and biosynthesis of multi-pass membrane proteins such as rhodopsin; independently, when present in Golgi/post-Golgi compartments of epithelial cells it mediates saturable Mg2+ transport, and in macrophages it suppresses lipid droplet accumulation via the GPR156 signaling axis to restrict Mycobacterium tuberculosis persistence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MMGT1 (EMC5/EMC5) is a two-transmembrane subunit of the ER membrane complex (EMC) that supports the co-translational biogenesis of multi-pass membrane proteins [#2, #3]. Within the EMC, the yeast ortholog Emc5 contributes to a five-transmembrane-helix fold centered on Emc3 that structurally resembles the prokaryotic YidC insertase and shapes a hydrophilic client-protein pocket required for transmembrane helix insertion [#2]. Consistent with an insertase role, loss of the Drosophila ortholog impairs rhodopsin biosynthesis and causes photoreceptor degeneration independent of the ERAD pathway [#3]. Independent of its EMC function, MMGT1 mediates saturable Mg2+ transport when heterologously expressed, with localization to the Golgi and post-Golgi/endosomal compartments that increases under low-magnesium conditions [#0, #1]. In macrophages, MMGT1 restricts lipid droplet accumulation through the orphan GPCR GPR156 axis, and its loss promotes Mycobacterium tuberculosis persistence via upregulated triacylglycerol synthesis [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established a first molecular function for MMGT1 by showing it can move Mg2+ across membranes, framing it as a candidate magnesium transporter.\",\n      \"evidence\": \"Heterologous expression in Xenopus oocytes with two-electrode voltage-clamp electrophysiology and fluorescence Mg2+ measurements\",\n      \"pmids\": [\"18057121\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single study, not independently replicated\",\n        \"Transport mechanism (channel vs carrier) and physiological substrate range unresolved\",\n        \"Does not reconcile transport activity with later EMC subunit role\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Placed the protein in the secretory pathway by mapping its localization to Golgi and post-Golgi vesicles and linking abundance to magnesium availability.\",\n      \"evidence\": \"Immunohistochemistry of HA-tagged MMgT1 in transfected COS-7 cells with real-time RT-PCR and fractionation\",\n      \"pmids\": [\"18057121\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relies on overexpressed tagged protein in a single lab\",\n        \"Does not establish endogenous localization or ER-resident EMC pool\",\n        \"Mechanism linking low Mg2+ to increased expression unknown\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated an in vivo requirement of the EMC5 ortholog for membrane protein biogenesis, showing rhodopsin synthesis depends on it independent of ERAD.\",\n      \"evidence\": \"Genome-wide genetic screen and loss-of-function alleles in Drosophila with phototransduction assays and ERAD epistasis\",\n      \"pmids\": [\"31263175\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Client repertoire beyond rhodopsin not defined\",\n        \"Molecular step (insertion vs folding vs stability) not resolved in this system\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved the structural basis of EMC5 function, showing it forms part of a YidC-like transmembrane insertase architecture that creates a client pocket for TMH insertion.\",\n      \"evidence\": \"Cryo-EM structure of S. cerevisiae EMC with validating mutagenesis\",\n      \"pmids\": [\"32494008\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure is of the yeast complex; human MMGT1-specific contacts inferred\",\n        \"Does not address the reported Golgi Mg2+ transport activity\",\n        \"Dynamics of client engagement not captured\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected MMGT1 to host defense, showing it suppresses macrophage lipid droplet accumulation through GPR156 to limit M. tuberculosis persistence.\",\n      \"evidence\": \"Genome-wide CRISPR screen, MMGT1-knockout macrophages, transcriptomics, lipid droplet imaging, and pharmacological targeting of triacylglycerol synthesis\",\n      \"pmids\": [\"37269834\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanistic link between MMGT1 loss and GPR156 induction not defined\",\n        \"Whether the phenotype derives from EMC insertase function or Mg2+ transport is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how MMGT1's role as an EMC insertase subunit relates mechanistically to its reported Golgi/post-Golgi Mg2+ transport activity and its macrophage lipid-droplet phenotype.\",\n      \"evidence\": \"No single study integrates the insertase, transport, and immunometabolic activities\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reconciliation of ER EMC localization with Golgi Mg2+ transport\",\n        \"Human structure and direct client list not established\",\n        \"Whether Mg2+ transport is an intrinsic activity or indirect remains open\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\n      \"ER membrane complex (EMC)\"\n    ],\n    \"partners\": [\n      \"EMC3\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}