{"gene":"MTX3","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2015,"finding":"MTX3 (human gene) was identified as a previously uncharacterized component of the mitochondrial intermembrane space bridging (MIB) complex, specifically residing in a membrane-bridging subcomplex (subcomplex B) together with SAMM50 and MTX2, distinct from the core MICOS complex and the complete MIB complex.","method":"Mitochondrial protein complexome profiling (native gel electrophoresis / mass spectrometry fractionation); comparative genomics across species","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 — complexome profiling with MS identification, single study, no reciprocal Co-IP or mutagenesis","pmids":["26477565"],"is_preprint":false},{"year":2004,"finding":"Zebrafish metaxin 3 (mtx3), an ortholog of human MTX3 located at 5q14.1 near THBS4, encodes a 313-amino acid protein containing a glutathione S-transferase (GST) domain and predominantly alpha-helical secondary structure, sharing 40% identity with MTX1 and 26% with MTX2, establishing the domain architecture of the MTX3 protein family.","method":"cDNA cloning, amino acid sequence alignment, domain analysis (GST domain, thioredoxin-like domain search), phylogenetic tree construction","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 — sequence and domain characterization of zebrafish ortholog, single study with computational and sequence-based validation","pmids":["15087125"],"is_preprint":false}],"current_model":"MTX3 is a component of the mitochondrial intermembrane space bridging (MIB) complex, where it localizes to a membrane-bridging subcomplex with SAMM50 and MTX2; structurally, it contains a glutathione S-transferase (GST) domain and is evolutionarily related to metaxins 1 and 2, though its precise molecular function within the MIB complex remains to be fully characterized."},"narrative":{"teleology":[{"year":2004,"claim":"Cloning and domain analysis of zebrafish mtx3 established that the metaxin family has a third member with a conserved GST domain and predominantly alpha-helical structure, defining the protein's architecture before any functional data existed.","evidence":"cDNA cloning, sequence alignment, and domain prediction in zebrafish","pmids":["15087125"],"confidence":"Medium","gaps":["No functional assay performed; domain architecture alone does not demonstrate enzymatic or structural activity","Human MTX3 protein not directly characterized in this study","Whether the GST domain possesses catalytic transferase activity is untested"]},{"year":2015,"claim":"Complexome profiling placed human MTX3 within a specific membrane-bridging subcomplex of the MIB complex alongside SAMM50 and MTX2, establishing its physical context in mitochondrial architecture.","evidence":"Native gel electrophoresis coupled to mass spectrometry fractionation of mitochondrial protein complexes","pmids":["26477565"],"confidence":"Medium","gaps":["No reciprocal co-immunoprecipitation or mutagenesis to validate direct protein–protein interactions","Functional consequence of MTX3 depletion on MIB complex integrity or mitochondrial morphology is unknown","Whether MTX3 contacts the inner membrane MICOS subunits or only outer membrane components is unresolved"]},{"year":null,"claim":"The molecular function of MTX3 — whether it acts as a structural scaffold, enzymatic component, or regulatory subunit within the MIB complex — remains entirely uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function or gain-of-function studies exist for MTX3 in any organism","No substrate or binding partner beyond complex co-migration has been identified","Role of the GST domain (catalytic vs. structural) is untested"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":["MIB complex (subcomplex B)"],"partners":["SAMM50","MTX2"],"other_free_text":[]},"mechanistic_narrative":"MTX3 is a mitochondrial protein containing a glutathione S-transferase (GST) domain that belongs to the metaxin family, sharing 40% identity with MTX1 and 26% with MTX2 [PMID:15087125]. It resides in a membrane-bridging subcomplex (subcomplex B) of the mitochondrial intermembrane space bridging (MIB) complex together with SAMM50 and MTX2, distinct from the core MICOS complex [PMID:26477565]. Its precise molecular function within the MIB complex is uncharacterized."},"prefetch_data":{"uniprot":{"accession":"Q5HYI7","full_name":"Metaxin-3","aliases":[],"length_aa":312,"mass_kda":35.1,"function":"Could function in transport of proteins into the mitochondrion","subcellular_location":"Mitochondrion; Mitochondrion outer membrane","url":"https://www.uniprot.org/uniprotkb/Q5HYI7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MTX3","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MTX3","total_profiled":1310},"omim":[{"mim_id":"619336","title":"METAXIN 3; MTX3","url":"https://www.omim.org/entry/619336"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mitochondria","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MTX3"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q5HYI7","domains":[{"cath_id":"1.20.1050.130","chopping":"4-244","consensus_level":"medium","plddt":92.5882,"start":4,"end":244}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5HYI7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5HYI7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5HYI7-F1-predicted_aligned_error_v6.png","plddt_mean":84.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MTX3","jax_strain_url":"https://www.jax.org/strain/search?query=MTX3"},"sequence":{"accession":"Q5HYI7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5HYI7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5HYI7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5HYI7"}},"corpus_meta":[{"pmid":"19139435","id":"PMC_19139435","title":"Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group.","date":"2009","source":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/19139435","citation_count":165,"is_preprint":false},{"pmid":"26477565","id":"PMC_26477565","title":"Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.","date":"2015","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/26477565","citation_count":159,"is_preprint":false},{"pmid":"27885668","id":"PMC_27885668","title":"Characterization of Gambierdiscus lapillus sp. nov. 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complexome profiling (native gel electrophoresis / mass spectrometry fractionation); comparative genomics across species\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — complexome profiling with MS identification, single study, no reciprocal Co-IP or mutagenesis\",\n      \"pmids\": [\"26477565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Zebrafish metaxin 3 (mtx3), an ortholog of human MTX3 located at 5q14.1 near THBS4, encodes a 313-amino acid protein containing a glutathione S-transferase (GST) domain and predominantly alpha-helical secondary structure, sharing 40% identity with MTX1 and 26% with MTX2, establishing the domain architecture of the MTX3 protein family.\",\n      \"method\": \"cDNA cloning, amino acid sequence alignment, domain analysis (GST domain, thioredoxin-like domain search), phylogenetic tree construction\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — sequence and domain characterization of zebrafish ortholog, single study with computational and sequence-based validation\",\n      \"pmids\": [\"15087125\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MTX3 is a component of the mitochondrial intermembrane space bridging (MIB) complex, where it localizes to a membrane-bridging subcomplex with SAMM50 and MTX2; structurally, it contains a glutathione S-transferase (GST) domain and is evolutionarily related to metaxins 1 and 2, though its precise molecular function within the MIB complex remains to be fully characterized.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MTX3 is a mitochondrial protein containing a glutathione S-transferase (GST) domain that belongs to the metaxin family, sharing 40% identity with MTX1 and 26% with MTX2 [PMID:15087125]. It resides in a membrane-bridging subcomplex (subcomplex B) of the mitochondrial intermembrane space bridging (MIB) complex together with SAMM50 and MTX2, distinct from the core MICOS complex [PMID:26477565]. Its precise molecular function within the MIB complex is uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Cloning and domain analysis of zebrafish mtx3 established that the metaxin family has a third member with a conserved GST domain and predominantly alpha-helical structure, defining the protein's architecture before any functional data existed.\",\n      \"evidence\": \"cDNA cloning, sequence alignment, and domain prediction in zebrafish\",\n      \"pmids\": [\"15087125\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay performed; domain architecture alone does not demonstrate enzymatic or structural activity\",\n        \"Human MTX3 protein not directly characterized in this study\",\n        \"Whether the GST domain possesses catalytic transferase activity is untested\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Complexome profiling placed human MTX3 within a specific membrane-bridging subcomplex of the MIB complex alongside SAMM50 and MTX2, establishing its physical context in mitochondrial architecture.\",\n      \"evidence\": \"Native gel electrophoresis coupled to mass spectrometry fractionation of mitochondrial protein complexes\",\n      \"pmids\": [\"26477565\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal co-immunoprecipitation or mutagenesis to validate direct protein–protein interactions\",\n        \"Functional consequence of MTX3 depletion on MIB complex integrity or mitochondrial morphology is unknown\",\n        \"Whether MTX3 contacts the inner membrane MICOS subunits or only outer membrane components is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of MTX3 — whether it acts as a structural scaffold, enzymatic component, or regulatory subunit within the MIB complex — remains entirely uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function or gain-of-function studies exist for MTX3 in any organism\",\n        \"No substrate or binding partner beyond complex co-migration has been identified\",\n        \"Role of the GST domain (catalytic vs. structural) is untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"MIB complex (subcomplex B)\"],\n    \"partners\": [\"SAMM50\", \"MTX2\"],\n    \"other_free_text\": []\n  }\n}\n```"}