{"gene":"TG_211460","gene_symbol":"MYR4","run_date":"2026-09-05T22:31:42","timeline":{"discoveries":[{"year":2020,"finding":"MYR4 (TGGT1_211460) was identified as a MYR1-interacting protein residing in the parasitophorous vacuole (PV), discovered by affinity purification/co-immunoprecipitation of MYR1.","method":"Affinity purification / co-immunoprecipitation of MYR1 followed by mass spectrometry","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with mass spectrometry identification, single lab, PV localization established","pmids":["32075880"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":2020,"finding":"MYR4 is essential for the translocation of the Toxoplasma effector protein GRA16 across the parasitophorous vacuole membrane into the host cell, and for the upregulation of host c-Myc and cyclin E1 in infected cells, as shown by loss-of-function analysis.","method":"Genetic knockout / loss-of-function with GRA16 translocation assay and host c-Myc/cyclin E1 upregulation readout","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (effector translocation and host gene upregulation), single lab","pmids":["32075880"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":2020,"finding":"MYR4 localizes to the parasitophorous vacuole (PV), placing it at the site of effector translocation across the PV membrane.","method":"Subcellular localization via affinity purification and immunofluorescence (implied by PV-localized protein identification)","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, localization inferred from affinity purification context; direct imaging methods not explicitly detailed in abstract","pmids":["32075880"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]}],"current_model":"MYR4 is a parasitophorous vacuole-localized protein that physically interacts with MYR1 and is required for the translocation of dense granule effectors (e.g., GRA16) across the PV membrane into the host cell, thereby enabling downstream host cell remodeling events such as upregulation of c-Myc and cyclin E1."},"narrative":{"mechanistic_narrative":"MYR4 is a Toxoplasma gondii parasitophorous vacuole (PV) protein that functions as a component of the machinery translocating dense granule effectors across the PV membrane into the host cell [PMID:32075880]. It was identified as a MYR1-interacting partner by reciprocal co-immunoprecipitation and mass spectrometry, physically linking it to the known MYR translocation apparatus at the PV [PMID:32075880]. Genetic loss of MYR4 abolishes translocation of the effector GRA16 into the host cell and prevents the downstream host response of c-Myc and cyclin E1 upregulation, establishing MYR4 as required for effector export and effector-driven host remodeling [PMID:32075880]. Beyond its PV localization, its interaction with MYR1, and its requirement for GRA16 export, no further mechanistic detail — including its precise biochemical role in the translocation process — has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Whether additional proteins besides MYR1 form the effector translocation apparatus was unresolved; identifying MYR4 as a MYR1-interacting PV protein defined a new component of this machinery.","evidence":"Affinity purification / reciprocal co-immunoprecipitation of MYR1 followed by mass spectrometry, in T. gondii GT1","pmids":["32075880"],"confidence":"Medium","gaps":["Stoichiometry and architecture of the MYR1-MYR4 complex not defined","Whether the interaction is direct or bridged by other proteins not established"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":2020,"claim":"Whether MYR4 is functionally required for effector export was unknown; loss-of-function showed it is essential for GRA16 translocation and the resulting host c-Myc/cyclin E1 upregulation, establishing its role in effector-driven host remodeling.","evidence":"Genetic knockout with GRA16 translocation assay and host c-Myc/cyclin E1 readout, in T. gondii GT1","pmids":["32075880"],"confidence":"Medium","gaps":["Whether MYR4 is required for translocation of effectors other than GRA16 not tested","Biochemical step in translocation controlled by MYR4 unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":2020,"claim":"Localizing MYR4 to the PV placed it physically at the site where effectors cross the PV membrane, consistent with a direct translocation role.","evidence":"Subcellular localization inferred from affinity purification context, in T. gondii GT1","pmids":["32075880"],"confidence":"Low","gaps":["PV localization inferred from affinity purification rather than confirmed by direct high-resolution imaging in this record","Whether MYR4 spans or associates with the PV membrane not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":null,"claim":"The precise molecular mechanism by which MYR4 promotes effector passage across the PV membrane, and the full set of effectors it exports, remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the MYR translocation apparatus","No biochemical activity assigned to MYR4","Effector repertoire dependent on MYR4 beyond GRA16 uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MYR translocation apparatus (MYR1-MYR4)"],"partners":["MYR1"],"other_free_text":["Required for translocation of the effector GRA16 into the host cell [#1]","Required for host c-Myc and cyclin E1 upregulation during infection [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"32075880","id":"PMC_32075880","title":"Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells.","date":"2020","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/32075880","citation_count":53,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3076,"output_tokens":785,"usd":0.010502,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5511,"output_tokens":1674,"usd":0.034702,"stage2_stop_reason":"end_turn"},"total_usd":0.045204,"stage1_batch_id":"msgbatch_01XFXJD6iZecXyWn9uU5Qom9","stage2_batch_id":"msgbatch_013GToKgs4AKSCRE4yvueviH","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"MYR4 (TGGT1_211460) was identified as a MYR1-interacting protein residing in the parasitophorous vacuole (PV), discovered by affinity purification/co-immunoprecipitation of MYR1.\",\n      \"method\": \"Affinity purification / co-immunoprecipitation of MYR1 followed by mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with mass spectrometry identification, single lab, PV localization established\",\n      \"pmids\": [\"32075880\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MYR4 is essential for the translocation of the Toxoplasma effector protein GRA16 across the parasitophorous vacuole membrane into the host cell, and for the upregulation of host c-Myc and cyclin E1 in infected cells, as shown by loss-of-function analysis.\",\n      \"method\": \"Genetic knockout / loss-of-function with GRA16 translocation assay and host c-Myc/cyclin E1 upregulation readout\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (effector translocation and host gene upregulation), single lab\",\n      \"pmids\": [\"32075880\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MYR4 localizes to the parasitophorous vacuole (PV), placing it at the site of effector translocation across the PV membrane.\",\n      \"method\": \"Subcellular localization via affinity purification and immunofluorescence (implied by PV-localized protein identification)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, localization inferred from affinity purification context; direct imaging methods not explicitly detailed in abstract\",\n      \"pmids\": [\"32075880\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    }\n  ],\n  \"current_model\": \"MYR4 is a parasitophorous vacuole-localized protein that physically interacts with MYR1 and is required for the translocation of dense granule effectors (e.g., GRA16) across the PV membrane into the host cell, thereby enabling downstream host cell remodeling events such as upregulation of c-Myc and cyclin E1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYR4 is a Toxoplasma gondii parasitophorous vacuole (PV) protein that functions as a component of the machinery translocating dense granule effectors across the PV membrane into the host cell [#0, #1]. It was identified as a MYR1-interacting partner by reciprocal co-immunoprecipitation and mass spectrometry, physically linking it to the known MYR translocation apparatus at the PV [#0]. Genetic loss of MYR4 abolishes translocation of the effector GRA16 into the host cell and prevents the downstream host response of c-Myc and cyclin E1 upregulation, establishing MYR4 as required for effector export and effector-driven host remodeling [#1]. Beyond its PV localization, its interaction with MYR1, and its requirement for GRA16 export, no further mechanistic detail — including its precise biochemical role in the translocation process — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether additional proteins besides MYR1 form the effector translocation apparatus was unresolved; identifying MYR4 as a MYR1-interacting PV protein defined a new component of this machinery.\",\n      \"evidence\": \"Affinity purification / reciprocal co-immunoprecipitation of MYR1 followed by mass spectrometry, in T. gondii GT1\",\n      \"pmids\": [\"32075880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and architecture of the MYR1-MYR4 complex not defined\", \"Whether the interaction is direct or bridged by other proteins not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether MYR4 is functionally required for effector export was unknown; loss-of-function showed it is essential for GRA16 translocation and the resulting host c-Myc/cyclin E1 upregulation, establishing its role in effector-driven host remodeling.\",\n      \"evidence\": \"Genetic knockout with GRA16 translocation assay and host c-Myc/cyclin E1 readout, in T. gondii GT1\",\n      \"pmids\": [\"32075880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether MYR4 is required for translocation of effectors other than GRA16 not tested\", \"Biochemical step in translocation controlled by MYR4 unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Localizing MYR4 to the PV placed it physically at the site where effectors cross the PV membrane, consistent with a direct translocation role.\",\n      \"evidence\": \"Subcellular localization inferred from affinity purification context, in T. gondii GT1\",\n      \"pmids\": [\"32075880\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"PV localization inferred from affinity purification rather than confirmed by direct high-resolution imaging in this record\", \"Whether MYR4 spans or associates with the PV membrane not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular mechanism by which MYR4 promotes effector passage across the PV membrane, and the full set of effectors it exports, remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of the MYR translocation apparatus\", \"No biochemical activity assigned to MYR4\", \"Effector repertoire dependent on MYR4 beyond GRA16 uncharacterized\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"parasitophorous vacuole\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"dense granule effector translocation across the parasitophorous vacuole membrane\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]}\n    ],\n    \"complexes\": [\"MYR translocation apparatus (MYR1-MYR4)\"],\n    \"partners\": [\"MYR1\"],\n    \"other_free_text\": [\n      \"Required for translocation of the effector GRA16 into the host cell [#1]\",\n      \"Required for host c-Myc and cyclin E1 upregulation during infection [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_211460","name":"MYR4","product":"Myc-regulation protein MYR4","uniprot_acc":"A0A125YMI0","chromosome":"TGME49_chrIV","start_pos":1696412},{"strain":"GT1","gene_id":"TGGT1_211460","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":1626832},{"strain":"RH88","gene_id":"TGRH88_008580","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023085","start_pos":1718929},{"strain":"VEG","gene_id":"TGVEG_211460","name":null,"product":"hypothetical protein","uniprot_acc":"V4YMX1","chromosome":"TGVEG_chrIV","start_pos":1721194}]}