{"gene":"TG_263090","gene_symbol":"","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2016,"finding":"Tg14-3-3 was identified by chromatography and mass spectrometry as a mediator of DC hypermotility. Parasite-derived fractions enriched for Tg14-3-3, recombinant Tg14-3-3 introduced by protein transfection, and lentiviral gene transfer of Tg14-3-3 were each sufficient to induce the hypermotile phenotype in murine DCs, human DCs, and microglia. Overexpression of Tg14-3-3 in parasites using a ligand-regulatable system correlated with induction of hypermotility in parasitized DCs.","method":"Chromatography, mass spectrometry, protein transfection, lentiviral gene transfer, ligand-regulatable overexpression system","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (biochemical fractionation/MS identification, recombinant protein transfection, lentiviral gene transfer, regulatable overexpression) all converging on the same functional phenotype in a single study","pmids":["27018989"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"In T. gondii-infected DCs, Tg14-3-3 was localized within the parasitophorous vacuolar space, and host cell 14-3-3 was rapidly recruited to the parasitophorous vacuole membrane, as determined by localization studies in infected DCs.","method":"Immunofluorescence/localization studies in infected dendritic cells","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in infected cells, single lab, single method, but functionally contextualized within the same study","pmids":["27018989"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2003,"finding":"T. gondii 14-3-3 protein localizes to the cytosol, membrane fraction, and Triton X-100-resistant lipid raft membranes of tachyzoites. Two isoforms were detected: the major isoform is mainly cytoplasmic with some membrane association, and the minor isoform associates with detergent-resistant lipid rafts.","method":"Immunofluorescence microscopy, subcellular fractionation, SDS-PAGE/Western blotting with isoform-specific detection","journal":"FEMS microbiology letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct subcellular fractionation and immunofluorescence, single lab, two orthogonal methods","pmids":["12892878"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2004,"finding":"Tg14-3-3 is present in the parasitophorous vacuole of T. gondii-infected human monocyte cells and is found in excreted/secreted antigens (ESA). The secretion of 14-3-3 was not sensitive to cycloheximide, indicating it is not dependent on ongoing protein synthesis and is released from a pre-existing pool.","method":"Western blotting of ESA fractions, immunolocalization in infected monocytes, cycloheximide inhibition assay","journal":"FEMS microbiology letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct biochemical and localization experiments, single lab, two orthogonal methods","pmids":["15109715"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2001,"finding":"A T. gondii 14-3-3 protein homologue expressed in feline enteroepithelial-stage parasites was able to complement the function of 14-3-3 protein in a Saccharomyces cerevisiae mutant (strain DS9-22), demonstrating functional conservation of the 14-3-3 domain.","method":"Yeast complementation assay, cDNA cloning, immunofluorescence assay","journal":"Veterinary parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional complementation assay is rigorous, but performed in a heterologous yeast system, single lab","pmids":["11182236"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Using yeast two-hybrid screening of a human cDNA library with Tg14-3-3 (RH strain) as bait, two host proteins were identified as Tg14-3-3 interactors: hCG1821272 and eIF5B (eukaryotic translation initiation factor 5B), implicating Tg14-3-3 in modulating host translational initiation and cell migration pathways.","method":"Yeast two-hybrid system (Y2HS), Western blotting for bait protein validation","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single yeast two-hybrid screen, single lab, no confirmatory pull-down or co-IP in mammalian cells reported","pmids":["29502294"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"T. gondii 14-3-3 (Tg14-3-3) is a parasite-derived effector protein that localizes to the cytosol, membranes, and lipid rafts of tachyzoites, is actively secreted into the parasitophorous vacuole and extracellular space from a pre-existing pool, and directly induces hypermotility in infected dendritic cells and microglia—thereby facilitating parasite dissemination via a 'Trojan horse' mechanism—while also binding host proteins eIF5B and hCG1821272, suggesting additional roles in manipulating host cell translation and migration signaling."},"narrative":{"mechanistic_narrative":"The Toxoplasma gondii 14-3-3 protein (Tg14-3-3) is a parasite-derived effector that drives host cell hypermotility to promote dissemination [PMID:27018989]. Tg14-3-3 introduced into cells by parasite-derived fractions, recombinant protein transfection, lentiviral transfer, or regulatable parasite overexpression is each sufficient to induce a hypermotile phenotype in murine and human dendritic cells and microglia, consistent with a 'Trojan horse' mode of spread [PMID:27018989]. In tachyzoites, the protein partitions between the cytosol, the membrane fraction, and Triton X-100-resistant lipid raft membranes, with a major cytoplasmic isoform and a minor raft-associated isoform [PMID:12892878]. Tg14-3-3 is secreted into the parasitophorous vacuole and released as an excreted/secreted antigen from a pre-existing pool, independent of ongoing protein synthesis [PMID:15109715, PMID:27018989]; host 14-3-3 is concurrently recruited to the parasitophorous vacuole membrane in infected dendritic cells [PMID:27018989]. The 14-3-3 domain is functionally conserved, complementing a Saccharomyces cerevisiae 14-3-3 mutant [PMID:11182236]. Host interactors identified for Tg14-3-3 include the translation initiation factor eIF5B and hCG1821272, linking it to host translation and migration signaling [PMID:29502294].","teleology":[{"year":2001,"claim":"Establishing whether the parasite 14-3-3 homologue is a bona fide functional 14-3-3 rather than a divergent sequence, yeast complementation showed the domain is functionally conserved.","evidence":"Yeast complementation of a S. cerevisiae 14-3-3 mutant with T. gondii cDNA, plus cloning and immunofluorescence","pmids":["11182236"],"confidence":"Medium","gaps":["Complementation performed in a heterologous yeast system, not in the parasite","Native binding partners and phosphopeptide targets not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2003,"claim":"To place the protein subcellularly, fractionation revealed cytosolic, membrane, and lipid-raft pools and two isoforms, hinting at compartment-specific roles.","evidence":"Immunofluorescence, subcellular fractionation, and isoform-specific Western blotting of tachyzoites","pmids":["12892878"],"confidence":"Medium","gaps":["Functional distinction between the two isoforms not resolved","Basis of lipid-raft association not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2004,"claim":"Whether the protein reaches the host cell was answered by detecting it in the parasitophorous vacuole and excreted/secreted antigens, released from a pre-existing pool.","evidence":"Western blotting of ESA fractions, immunolocalization in infected monocytes, and cycloheximide inhibition assay","pmids":["15109715"],"confidence":"Medium","gaps":["Secretion pathway and route of release unknown","No host target of secreted protein identified at this stage"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"The central functional question — what Tg14-3-3 does to the host cell — was answered by showing it is sufficient to induce dendritic cell and microglial hypermotility, providing an effector for the Trojan-horse dissemination model.","evidence":"Chromatography/MS identification, recombinant protein transfection, lentiviral transfer, and regulatable overexpression converging on hypermotility; localization in infected DCs","pmids":["27018989"],"confidence":"High","gaps":["Downstream host signaling driving hypermotility not defined","Direct host binding partner mediating motility not identified","Recruitment of host 14-3-3 to the vacuole membrane mechanistically unexplained"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"To identify host machinery targeted by the effector, a yeast two-hybrid screen nominated eIF5B and hCG1821272, implicating host translation and migration pathways.","evidence":"Yeast two-hybrid screen of a human cDNA library with RH-strain Tg14-3-3 bait, with Western blot bait validation","pmids":["29502294"],"confidence":"Low","gaps":["Single Y2H screen without confirmatory co-IP or pull-down in mammalian cells","Functional consequence of the interactions on host translation or motility not tested","Link between these interactors and the hypermotility phenotype not established"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":null,"claim":"How secreted Tg14-3-3 mechanistically triggers host hypermotility and whether the eIF5B/hCG1821272 interactions execute this remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No validated host signaling pathway connecting Tg14-3-3 to motility","Phosphopeptide-binding activity of Tg14-3-3 in host cells untested","Secretion mechanism and role of the two tachyzoite isoforms unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["HOST EIF5B (EUKARYOTIC TRANSLATION INITIATION FACTOR 5B) [#5]","HOST HCG1821272 [#5]","HOST 14-3-3 RECRUITED TO PARASITOPHOROUS VACUOLE MEMBRANE [#1]"],"other_free_text":["Tg14-3-3 is a secreted parasite effector sufficient to induce hypermotility in dendritic cells and microglia, supporting a Trojan-horse dissemination model [#0].","Secretion is independent of ongoing protein synthesis, indicating release from a pre-existing pool [#3].","The 14-3-3 domain is functionally conserved as shown by complementation of a yeast 14-3-3 mutant [#4]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23181694","id":"PMC_23181694","title":"Evaluation of protective immune responses induced by DNA vaccines encoding Toxoplasma gondii surface antigen 1 (SAG1) and 14-3-3 protein in BALB/c mice.","date":"2012","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/23181694","citation_count":72,"is_preprint":false},{"pmid":"27018989","id":"PMC_27018989","title":"Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27018989","citation_count":44,"is_preprint":false},{"pmid":"12892878","id":"PMC_12892878","title":"Subcellular localization of 14-3-3 proteins in Toxoplasma gondii tachyzoites and evidence for a lipid raft-associated form.","date":"2003","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/12892878","citation_count":32,"is_preprint":false},{"pmid":"15109715","id":"PMC_15109715","title":"Characterization of an excreted/secreted antigen form of 14-3-3 protein in Toxoplasma gondii tachyzoites.","date":"2004","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/15109715","citation_count":32,"is_preprint":false},{"pmid":"28064210","id":"PMC_28064210","title":"Characteristics of autoantibodies targeting 14-3-3 proteins and their association with clinical features in newly diagnosed giant cell arteritis.","date":"2017","source":"Rheumatology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/28064210","citation_count":24,"is_preprint":false},{"pmid":"11182236","id":"PMC_11182236","title":"A 14-3-3 protein homologue is expressed in feline enteroepithelial-stages of Toxoplasma gondii.","date":"2001","source":"Veterinary parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11182236","citation_count":17,"is_preprint":false},{"pmid":"35003067","id":"PMC_35003067","title":"Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Recombinant Toxoplasma gondii MIF, CDPK3, and 14-3-3 Protein Cocktail Vaccine.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35003067","citation_count":13,"is_preprint":false},{"pmid":"11073080","id":"PMC_11073080","title":"Antigens expressed in feline enteroepithelial-stages parasites of Toxoplasma gondii.","date":"2000","source":"The Journal of veterinary medical science","url":"https://pubmed.ncbi.nlm.nih.gov/11073080","citation_count":5,"is_preprint":false},{"pmid":"29502294","id":"PMC_29502294","title":"Identification of two novel host proteins interacting with Toxoplasma gondii 14-3-3 protein by yeast two-hybrid system.","date":"2018","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/29502294","citation_count":2,"is_preprint":false},{"pmid":"23484253","id":"PMC_23484253","title":"[Construction and expression of an eukaryote vector of 14-3-3 protein in Toxoplasma gondii].","date":"2012","source":"Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases","url":"https://pubmed.ncbi.nlm.nih.gov/23484253","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7513,"output_tokens":1775,"usd":0.024582,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6877,"output_tokens":2847,"usd":0.05278,"stage2_stop_reason":"end_turn"},"total_usd":0.077362,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"Tg14-3-3 was identified by chromatography and mass spectrometry as a mediator of DC hypermotility. Parasite-derived fractions enriched for Tg14-3-3, recombinant Tg14-3-3 introduced by protein transfection, and lentiviral gene transfer of Tg14-3-3 were each sufficient to induce the hypermotile phenotype in murine DCs, human DCs, and microglia. Overexpression of Tg14-3-3 in parasites using a ligand-regulatable system correlated with induction of hypermotility in parasitized DCs.\",\n      \"method\": \"Chromatography, mass spectrometry, protein transfection, lentiviral gene transfer, ligand-regulatable overexpression system\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (biochemical fractionation/MS identification, recombinant protein transfection, lentiviral gene transfer, regulatable overexpression) all converging on the same functional phenotype in a single study\",\n      \"pmids\": [\"27018989\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In T. gondii-infected DCs, Tg14-3-3 was localized within the parasitophorous vacuolar space, and host cell 14-3-3 was rapidly recruited to the parasitophorous vacuole membrane, as determined by localization studies in infected DCs.\",\n      \"method\": \"Immunofluorescence/localization studies in infected dendritic cells\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in infected cells, single lab, single method, but functionally contextualized within the same study\",\n      \"pmids\": [\"27018989\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"T. gondii 14-3-3 protein localizes to the cytosol, membrane fraction, and Triton X-100-resistant lipid raft membranes of tachyzoites. Two isoforms were detected: the major isoform is mainly cytoplasmic with some membrane association, and the minor isoform associates with detergent-resistant lipid rafts.\",\n      \"method\": \"Immunofluorescence microscopy, subcellular fractionation, SDS-PAGE/Western blotting with isoform-specific detection\",\n      \"journal\": \"FEMS microbiology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct subcellular fractionation and immunofluorescence, single lab, two orthogonal methods\",\n      \"pmids\": [\"12892878\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Tg14-3-3 is present in the parasitophorous vacuole of T. gondii-infected human monocyte cells and is found in excreted/secreted antigens (ESA). The secretion of 14-3-3 was not sensitive to cycloheximide, indicating it is not dependent on ongoing protein synthesis and is released from a pre-existing pool.\",\n      \"method\": \"Western blotting of ESA fractions, immunolocalization in infected monocytes, cycloheximide inhibition assay\",\n      \"journal\": \"FEMS microbiology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct biochemical and localization experiments, single lab, two orthogonal methods\",\n      \"pmids\": [\"15109715\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"A T. gondii 14-3-3 protein homologue expressed in feline enteroepithelial-stage parasites was able to complement the function of 14-3-3 protein in a Saccharomyces cerevisiae mutant (strain DS9-22), demonstrating functional conservation of the 14-3-3 domain.\",\n      \"method\": \"Yeast complementation assay, cDNA cloning, immunofluorescence assay\",\n      \"journal\": \"Veterinary parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional complementation assay is rigorous, but performed in a heterologous yeast system, single lab\",\n      \"pmids\": [\"11182236\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Using yeast two-hybrid screening of a human cDNA library with Tg14-3-3 (RH strain) as bait, two host proteins were identified as Tg14-3-3 interactors: hCG1821272 and eIF5B (eukaryotic translation initiation factor 5B), implicating Tg14-3-3 in modulating host translational initiation and cell migration pathways.\",\n      \"method\": \"Yeast two-hybrid system (Y2HS), Western blotting for bait protein validation\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single yeast two-hybrid screen, single lab, no confirmatory pull-down or co-IP in mammalian cells reported\",\n      \"pmids\": [\"29502294\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    }\n  ],\n  \"current_model\": \"T. gondii 14-3-3 (Tg14-3-3) is a parasite-derived effector protein that localizes to the cytosol, membranes, and lipid rafts of tachyzoites, is actively secreted into the parasitophorous vacuole and extracellular space from a pre-existing pool, and directly induces hypermotility in infected dendritic cells and microglia—thereby facilitating parasite dissemination via a 'Trojan horse' mechanism—while also binding host proteins eIF5B and hCG1821272, suggesting additional roles in manipulating host cell translation and migration signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"The Toxoplasma gondii 14-3-3 protein (Tg14-3-3) is a parasite-derived effector that drives host cell hypermotility to promote dissemination [#0]. Tg14-3-3 introduced into cells by parasite-derived fractions, recombinant protein transfection, lentiviral transfer, or regulatable parasite overexpression is each sufficient to induce a hypermotile phenotype in murine and human dendritic cells and microglia, consistent with a 'Trojan horse' mode of spread [#0]. In tachyzoites, the protein partitions between the cytosol, the membrane fraction, and Triton X-100-resistant lipid raft membranes, with a major cytoplasmic isoform and a minor raft-associated isoform [#2]. Tg14-3-3 is secreted into the parasitophorous vacuole and released as an excreted/secreted antigen from a pre-existing pool, independent of ongoing protein synthesis [#3, #1]; host 14-3-3 is concurrently recruited to the parasitophorous vacuole membrane in infected dendritic cells [#1]. The 14-3-3 domain is functionally conserved, complementing a Saccharomyces cerevisiae 14-3-3 mutant [#4]. Host interactors identified for Tg14-3-3 include the translation initiation factor eIF5B and hCG1821272, linking it to host translation and migration signaling [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing whether the parasite 14-3-3 homologue is a bona fide functional 14-3-3 rather than a divergent sequence, yeast complementation showed the domain is functionally conserved.\",\n      \"evidence\": \"Yeast complementation of a S. cerevisiae 14-3-3 mutant with T. gondii cDNA, plus cloning and immunofluorescence\",\n      \"pmids\": [\"11182236\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Complementation performed in a heterologous yeast system, not in the parasite\", \"Native binding partners and phosphopeptide targets not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"To place the protein subcellularly, fractionation revealed cytosolic, membrane, and lipid-raft pools and two isoforms, hinting at compartment-specific roles.\",\n      \"evidence\": \"Immunofluorescence, subcellular fractionation, and isoform-specific Western blotting of tachyzoites\",\n      \"pmids\": [\"12892878\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional distinction between the two isoforms not resolved\", \"Basis of lipid-raft association not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Whether the protein reaches the host cell was answered by detecting it in the parasitophorous vacuole and excreted/secreted antigens, released from a pre-existing pool.\",\n      \"evidence\": \"Western blotting of ESA fractions, immunolocalization in infected monocytes, and cycloheximide inhibition assay\",\n      \"pmids\": [\"15109715\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Secretion pathway and route of release unknown\", \"No host target of secreted protein identified at this stage\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The central functional question — what Tg14-3-3 does to the host cell — was answered by showing it is sufficient to induce dendritic cell and microglial hypermotility, providing an effector for the Trojan-horse dissemination model.\",\n      \"evidence\": \"Chromatography/MS identification, recombinant protein transfection, lentiviral transfer, and regulatable overexpression converging on hypermotility; localization in infected DCs\",\n      \"pmids\": [\"27018989\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream host signaling driving hypermotility not defined\", \"Direct host binding partner mediating motility not identified\", \"Recruitment of host 14-3-3 to the vacuole membrane mechanistically unexplained\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To identify host machinery targeted by the effector, a yeast two-hybrid screen nominated eIF5B and hCG1821272, implicating host translation and migration pathways.\",\n      \"evidence\": \"Yeast two-hybrid screen of a human cDNA library with RH-strain Tg14-3-3 bait, with Western blot bait validation\",\n      \"pmids\": [\"29502294\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Y2H screen without confirmatory co-IP or pull-down in mammalian cells\", \"Functional consequence of the interactions on host translation or motility not tested\", \"Link between these interactors and the hypermotility phenotype not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How secreted Tg14-3-3 mechanistically triggers host hypermotility and whether the eIF5B/hCG1821272 interactions execute this remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No validated host signaling pathway connecting Tg14-3-3 to motility\", \"Phosphopeptide-binding activity of Tg14-3-3 in host cells untested\", \"Secretion mechanism and role of the two tachyzoite isoforms unresolved\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019904\", \"supporting_discovery_ids\": [4, 5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0045121\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0020003\", \"supporting_discovery_ids\": [1, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0052126\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006413\", \"supporting_discovery_ids\": [5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"host eIF5B (eukaryotic translation initiation factor 5B) [#5]\", \"host hCG1821272 [#5]\", \"host 14-3-3 recruited to parasitophorous vacuole membrane [#1]\"],\n    \"other_free_text\": [\n      \"Tg14-3-3 is a secreted parasite effector sufficient to induce hypermotility in dendritic cells and microglia, supporting a Trojan-horse dissemination model [#0].\",\n      \"Secretion is independent of ongoing protein synthesis, indicating release from a pre-existing pool [#3].\",\n      \"The 14-3-3 domain is functionally conserved as shown by complementation of a yeast 14-3-3 mutant [#4].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_263090","name":null,"product":"14-3-3 protein","uniprot_acc":"A0A125YLJ4","chromosome":"TGME49_chrVIIb","start_pos":813162},{"strain":"GT1","gene_id":"TGGT1_263090","name":null,"product":"14-3-3 protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":786880},{"strain":"RH88","gene_id":"TGRH88_067940","name":null,"product":"14-3-3 protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":825281},{"strain":"VEG","gene_id":"TGVEG_263090","name":null,"product":"14-3-3 protein","uniprot_acc":"B9Q0N7","chromosome":"TGVEG_chrVIIb","start_pos":818668}]}