{"gene":"TG_239010","gene_symbol":"TEEGR","run_date":"2026-09-11T11:01:00","timeline":{"discoveries":[{"year":2019,"finding":"TEEGR (also called HCE1) is a dense granule-resident effector exported into the host cell nucleus where it complexes with host transcription factors E2F3 and E2F4 to induce gene expression, and also promotes EZH2 upregulation, which epigenetically silences a subset of NF-κB-regulated cytokines, counteracting NF-κB signalling and promoting parasite persistence in mice.","method":"Dense granule localization, host cell nuclear export assay, co-immunoprecipitation with E2F3/E2F4, EZH2 pathway functional assays, in vivo mouse persistence model","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, nuclear localization by direct experiment, genetic loss-of-function in vivo, multiple orthogonal methods in a single rigorous study","pmids":["31036909"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"HCE1/TEEGR drives host cell cycle G1-to-S transition as shown by FUCCI reporter kinetics; however, a subsequent S-phase block in DNA synthesis is not caused by HCE1/TEEGR or additional dense granule effectors but depends on host cell type and contact inhibition status.","method":"FUCCI fluorescence cell cycle reporter, HCE1/TEEGR knockout parasites, multiple host cell lines","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell FUCCI reporter with knockout parasites, single lab, distinguishes effector-dependent vs. host-context-dependent effects","pmids":["35587658"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"TEEGR counter-regulates GRA15/GRA24-driven CCR7-mediated macrophage chemotaxis (hypermigration) in parasitized macrophages, acting downstream or in opposition to NF-κB signalling induced by GRA15.","method":"Genetic knockout of individual effectors including TEEGR, macrophage chemotaxis and migration assays, NF-κB signalling readouts","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — effector knockout epistasis in primary macrophages, single lab, functional migration assay readout","pmids":["39207098"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"TEEGR counteracts GRA15-driven NF-κB-dependent CCL5 induction in brain endothelial cells and dendritic cells in an MYR-translocon-dependent manner, establishing TEEGR as a suppressor of the CCL5/CCR5 axis used by GRA15 for Toxoplasma CNS dissemination.","method":"GRA15 and TEEGR effector knockouts, MYR-translocon dependency assay, CCL5 secretion measurement, NF-κB signalling readouts in primary brain endothelial cells and DCs","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO epistasis with MYR-translocon dependency confirmed, functional CCL5 secretion readout, single lab","pmids":["41528135"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"HCE1/TEEGR is one of eight MYR1-dependent dense granule effectors that cooperatively and additively activate the non-canonical NF-κB pathway (RelB/p52) by driving TRAF3 depletion, NIK stabilization, p100 phosphorylation, and p52 processing; no single effector including HCE1/TEEGR is solely responsible for this phenotype.","method":"Combinatorial knockout panel of effectors, nuclear accumulation assays for RelB/p52, TRAF3/NIK western blotting, MYR1-dependency epistasis","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — combinatorial KO epistasis with multiple mechanistic readouts, single lab, establishes additive/cooperative role rather than sole responsibility","pmids":["42663465"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"HCE1/TEEGR is exported from the parasitophorous vacuole in a MYR1-dependent manner and localizes to the host nucleus, where it binds the cyclin E regulatory complex components DP1, E2F3, and E2F4, and is necessary and sufficient to upregulate cyclin E and E2F transcription factor target genes; parasites lacking HCE1/TEEGR exhibit a substantial growth defect.","method":"MYR1 knockout epistasis, immunoprecipitation of HCE1 from infected host cells, ectopic expression in Neospora caninum and uninfected HFFs, loss-of-function growth assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, epistasis with MYR1 KO, ectopic expression sufficiency test, loss-of-function phenotype, multiple orthogonal methods","pmids":["31040242"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"MYR1-dependent export of effectors (including HCE1/TEEGR) is required for early host S-phase arrest and double-strand DNA break induction within 15 min post-infection; deletion of HCE1 alone did not replicate this phenotype, indicating cyclin E1 upregulation is not the mechanism for this early DNA damage.","method":"TgΔmyr1 and TgΔhce1 knockout parasites, flow cytometry cell cycle analysis, γH2AX DNA damage foci imaging, kinetic time-course up to 3 h p.i.","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO epistasis with two mutants and orthogonal readouts; negative finding for HCE1 direct role in DNA damage is experimentally established","pmids":["39681694"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TEEGR/HCE1 is a Toxoplasma gondii dense granule effector exported into the host cell nucleus via the MYR1 translocon, where it binds host transcription factors E2F3, E2F4, and DP1 to drive cyclin E and E2F target gene expression, promotes EZH2-mediated epigenetic silencing of NF-κB-regulated cytokines to dampen canonical NF-κB-driven immune responses, counter-regulates GRA15-driven CCL5 and CCR7-mediated macrophage hypermigration, and cooperates additively with seven other MYR1-dependent effectors to activate the non-canonical NF-κB (RelB/p52) pathway, collectively facilitating parasite immune evasion and persistence in the host."},"narrative":{"mechanistic_narrative":"TEEGR (also called HCE1) is a Toxoplasma gondii dense granule effector that manipulates host cell transcription and immune signalling to promote parasite persistence [PMID:31036909]. After secretion, it is exported from the parasitophorous vacuole into the host nucleus in a MYR1-dependent manner, where it binds the host cyclin E regulatory complex components E2F3, E2F4, and DP1 and is both necessary and sufficient to upregulate cyclin E and E2F target genes, driving the host G1-to-S cell cycle transition; parasites lacking TEEGR show a substantial growth defect [PMID:31036909, PMID:31040242, PMID:35587658]. In parallel, TEEGR promotes EZH2 upregulation to epigenetically silence a subset of NF-κB-regulated cytokines, and it counter-regulates GRA15-driven NF-κB responses — suppressing CCR7-mediated macrophage hypermigration and the CCL5/CCR5 axis used for CNS dissemination in an MYR-translocon-dependent manner [PMID:31036909, PMID:39207098, PMID:41528135]. TEEGR also contributes, additively with seven other MYR1-dependent effectors, to activation of the non-canonical NF-κB (RelB/p52) pathway, though no single effector accounts for this phenotype [PMID:42663465].","teleology":[{"year":2019,"claim":"Established that TEEGR/HCE1 is a nuclear-targeted dense granule effector that rewires host transcription and dampens NF-κB immunity, defining it as a parasite persistence factor.","evidence":"Dense granule localization, host nuclear export, reciprocal Co-IP with E2F3/E2F4, EZH2 pathway assays, and in vivo mouse persistence model","pmids":["31036909"],"confidence":"High","gaps":["Direct binding site of TEEGR on E2F factors not mapped","Mechanism by which TEEGR drives EZH2 upregulation not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Resolved which host cell cycle events depend on TEEGR versus host context, attributing the G1-to-S transition to TEEGR but the subsequent S-phase block to host cell type and contact inhibition.","evidence":"FUCCI live-cell cell cycle reporter with TEEGR knockout parasites across multiple host cell lines","pmids":["35587658"],"confidence":"Medium","gaps":["Molecular basis of the host-context-dependent S-phase block unidentified","Single lab"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Positioned TEEGR as a counter-regulator of GRA15/GRA24-driven macrophage chemotaxis, showing it opposes NF-κB-induced CCR7-mediated hypermigration.","evidence":"Individual effector knockouts, macrophage chemotaxis/migration assays, and NF-κB readouts","pmids":["39207098"],"confidence":"Medium","gaps":["Whether TEEGR acts directly on the CCR7 axis or via its transcriptional/EZH2 activity not distinguished","Single lab"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"Extended TEEGR's immune-suppressive role to CNS dissemination, showing it suppresses GRA15-driven NF-κB-dependent CCL5 induction via the MYR translocon in brain endothelial cells and dendritic cells.","evidence":"GRA15 and TEEGR knockouts, MYR-translocon dependency assay, CCL5 secretion measurement, NF-κB readouts in primary brain endothelial cells and DCs","pmids":["41528135"],"confidence":"Medium","gaps":["In vivo relevance to CNS dissemination not directly tested","Single lab"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"Placed TEEGR within a cooperative effector network activating non-canonical NF-κB, showing it acts additively with seven other MYR1-dependent effectors rather than alone.","evidence":"Combinatorial effector knockout panel, RelB/p52 nuclear accumulation assays, TRAF3/NIK western blotting, MYR1-dependency epistasis","pmids":["42663465"],"confidence":"Medium","gaps":["The specific molecular contribution of TEEGR to TRAF3 depletion/NIK stabilization not isolated","Single lab"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Host cyclin E regulatory complex (E2F3/E2F4/DP1)"],"partners":["E2F3 (HOST)","E2F4 (HOST)","DP1 (HOST)","MYR1 (PARASITE TRANSLOCON, REQUIRED FOR EXPORT)","EZH2 (HOST, UPREGULATED)"],"other_free_text":["Exported via the MYR1/MYR translocon from the parasitophorous vacuole into the host nucleus [#1, #5]","Necessary and sufficient for cyclin E/E2F target gene upregulation; loss causes parasite growth defect [#1]","Counter-regulates GRA15-driven NF-κB outputs including CCR7-mediated macrophage hypermigration and CCL5/CCR5-axis-driven CNS dissemination [#3, #5]","Acts additively with seven other MYR1-dependent effectors in non-canonical NF-κB (RelB/p52) activation; not solely responsible [#6]","Not responsible for early MYR1-dependent S-phase arrest/DNA double-strand break induction [#4]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"31036909","id":"PMC_31036909","title":"The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.","date":"2019","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31036909","citation_count":81,"is_preprint":false},{"pmid":"39207098","id":"PMC_39207098","title":"Hypermigration of macrophages through the concerted action of GRA effectors on NF-κB/p38 signaling and host chromatin accessibility potentiates Toxoplasma dissemination.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/39207098","citation_count":13,"is_preprint":false},{"pmid":"35587658","id":"PMC_35587658","title":"Disruption of Toxoplasma gondii-Induced Host Cell DNA Replication Is Dependent on Contact Inhibition and Host Cell Type.","date":"2022","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/35587658","citation_count":5,"is_preprint":false},{"pmid":"41036225","id":"PMC_41036225","title":"Proteome changes during in vitro culture adaptation of Toxoplasma gondii archetypal II and III field isolates.","date":"2025","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41036225","citation_count":1,"is_preprint":false},{"pmid":"38370679","id":"PMC_38370679","title":"Hypermigration of macrophages through the concerted action of GRA effectors on NF-κB/p38 signaling and host chromatin accessibility potentiates Toxoplasma dissemination.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38370679","citation_count":1,"is_preprint":false},{"pmid":"41528135","id":"PMC_41528135","title":"Toxoplasma effector GRA15-driven CCL5 secretion enhances brain parasite load through microvascular sequestration of phagocytes.","date":"2026","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/41528135","citation_count":0,"is_preprint":false},{"pmid":"42663465","id":"PMC_42663465","title":"A suite of eight Toxoplasma gondii effectors cooperates to activate the non-canonical NF-κB pathway.","date":"2026","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/42663465","citation_count":0,"is_preprint":false},{"pmid":"41959509","id":"PMC_41959509","title":"A Suite of Eight Toxoplasma gondii Effectors Cooperates to Activate the Non-canonical NF-κB Pathway.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41959509","citation_count":0,"is_preprint":false},{"pmid":"31040242","id":"PMC_31040242","title":"Toxoplasma Controls Host Cyclin E Expression through the Use of a Novel MYR1-Dependent Effector Protein, HCE1.","date":"2019","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/31040242","citation_count":51,"is_preprint":false},{"pmid":"39681694","id":"PMC_39681694","title":"Toxoplasma gondii infection induces early host cell cycle arrest and DNA damage in primary human host cells by a MYR1-dependent mechanism.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39681694","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8372,"output_tokens":2117,"usd":0.028435,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7493,"output_tokens":3524,"usd":0.062783,"stage2_stop_reason":"end_turn"},"total_usd":0.095918,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"summary amended","hand_review_patch":"2026-09-11 AK hand-review verdicts (handoff/tools_2026-09-11/patch)","hand_review_verdict":"edit"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"TEEGR (also called HCE1) is a dense granule-resident effector exported into the host cell nucleus where it complexes with host transcription factors E2F3 and E2F4 to induce gene expression, and also promotes EZH2 upregulation, which epigenetically silences a subset of NF-κB-regulated cytokines, counteracting NF-κB signalling and promoting parasite persistence in mice.\",\n      \"method\": \"Dense granule localization, host cell nuclear export assay, co-immunoprecipitation with E2F3/E2F4, EZH2 pathway functional assays, in vivo mouse persistence model\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, nuclear localization by direct experiment, genetic loss-of-function in vivo, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"31036909\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"HCE1/TEEGR is exported from the parasitophorous vacuole in a MYR1-dependent manner and localizes to the host nucleus, where it binds the cyclin E regulatory complex components DP1, E2F3, and E2F4, and is necessary and sufficient to upregulate cyclin E and E2F transcription factor target genes; parasites lacking HCE1/TEEGR exhibit a substantial growth defect.\",\n      \"method\": \"MYR1 knockout epistasis, immunoprecipitation of HCE1 from infected host cells, ectopic expression in Neospora caninum and uninfected HFFs, loss-of-function growth assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, epistasis with MYR1 KO, ectopic expression sufficiency test, loss-of-function phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"31040242\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"HCE1/TEEGR drives host cell cycle G1-to-S transition as shown by FUCCI reporter kinetics; however, a subsequent S-phase block in DNA synthesis is not caused by HCE1/TEEGR or additional dense granule effectors but depends on host cell type and contact inhibition status.\",\n      \"method\": \"FUCCI fluorescence cell cycle reporter, HCE1/TEEGR knockout parasites, multiple host cell lines\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell FUCCI reporter with knockout parasites, single lab, distinguishes effector-dependent vs. host-context-dependent effects\",\n      \"pmids\": [\"35587658\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TEEGR counter-regulates GRA15/GRA24-driven CCR7-mediated macrophage chemotaxis (hypermigration) in parasitized macrophages, acting downstream or in opposition to NF-κB signalling induced by GRA15.\",\n      \"method\": \"Genetic knockout of individual effectors including TEEGR, macrophage chemotaxis and migration assays, NF-κB signalling readouts\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — effector knockout epistasis in primary macrophages, single lab, functional migration assay readout\",\n      \"pmids\": [\"39207098\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MYR1-dependent export of effectors (including HCE1/TEEGR) is required for early host S-phase arrest and double-strand DNA break induction within 15 min post-infection; deletion of HCE1 alone did not replicate this phenotype, indicating cyclin E1 upregulation is not the mechanism for this early DNA damage.\",\n      \"method\": \"TgΔmyr1 and TgΔhce1 knockout parasites, flow cytometry cell cycle analysis, γH2AX DNA damage foci imaging, kinetic time-course up to 3 h p.i.\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO epistasis with two mutants and orthogonal readouts; negative finding for HCE1 direct role in DNA damage is experimentally established\",\n      \"pmids\": [\"39681694\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TEEGR counteracts GRA15-driven NF-κB-dependent CCL5 induction in brain endothelial cells and dendritic cells in an MYR-translocon-dependent manner, establishing TEEGR as a suppressor of the CCL5/CCR5 axis used by GRA15 for Toxoplasma CNS dissemination.\",\n      \"method\": \"GRA15 and TEEGR effector knockouts, MYR-translocon dependency assay, CCL5 secretion measurement, NF-κB signalling readouts in primary brain endothelial cells and DCs\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO epistasis with MYR-translocon dependency confirmed, functional CCL5 secretion readout, single lab\",\n      \"pmids\": [\"41528135\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"HCE1/TEEGR is one of eight MYR1-dependent dense granule effectors that cooperatively and additively activate the non-canonical NF-κB pathway (RelB/p52) by driving TRAF3 depletion, NIK stabilization, p100 phosphorylation, and p52 processing; no single effector including HCE1/TEEGR is solely responsible for this phenotype.\",\n      \"method\": \"Combinatorial knockout panel of effectors, nuclear accumulation assays for RelB/p52, TRAF3/NIK western blotting, MYR1-dependency epistasis\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — combinatorial KO epistasis with multiple mechanistic readouts, single lab, establishes additive/cooperative role rather than sole responsibility\",\n      \"pmids\": [\"42663465\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TEEGR/HCE1 is a Toxoplasma gondii dense granule effector exported into the host cell nucleus via the MYR1 translocon, where it binds host transcription factors E2F3, E2F4, and DP1 to drive cyclin E and E2F target gene expression, promotes EZH2-mediated epigenetic silencing of NF-κB-regulated cytokines to dampen canonical NF-κB-driven immune responses, counter-regulates GRA15-driven CCL5 and CCR7-mediated macrophage hypermigration, and cooperates additively with seven other MYR1-dependent effectors to activate the non-canonical NF-κB (RelB/p52) pathway, collectively facilitating parasite immune evasion and persistence in the host.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TEEGR (also called HCE1) is a Toxoplasma gondii dense granule effector that manipulates host cell transcription and immune signalling to promote parasite persistence [#0, #1]. After secretion, it is exported from the parasitophorous vacuole into the host nucleus in a MYR1-dependent manner, where it binds the host cyclin E regulatory complex components E2F3, E2F4, and DP1 and is both necessary and sufficient to upregulate cyclin E and E2F target genes, driving the host G1-to-S cell cycle transition; parasites lacking TEEGR show a substantial growth defect [#0, #1, #2]. In parallel, TEEGR promotes EZH2 upregulation to epigenetically silence a subset of NF-\\u03baB-regulated cytokines, and it counter-regulates GRA15-driven NF-\\u03baB responses \\u2014 suppressing CCR7-mediated macrophage hypermigration and the CCL5/CCR5 axis used for CNS dissemination in an MYR-translocon-dependent manner [#0, #3, #5]. TEEGR also contributes, additively with seven other MYR1-dependent effectors, to activation of the non-canonical NF-\\u03baB (RelB/p52) pathway, though no single effector accounts for this phenotype [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established that TEEGR/HCE1 is a nuclear-targeted dense granule effector that rewires host transcription and dampens NF-\\u03baB immunity, defining it as a parasite persistence factor.\",\n      \"evidence\": \"Dense granule localization, host nuclear export, reciprocal Co-IP with E2F3/E2F4, EZH2 pathway assays, and in vivo mouse persistence model\",\n      \"pmids\": [\"31036909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding site of TEEGR on E2F factors not mapped\", \"Mechanism by which TEEGR drives EZH2 upregulation not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the export route and transcriptional output of TEEGR, showing MYR1-dependent nuclear delivery and that TEEGR is necessary and sufficient to activate cyclin E/E2F target genes.\",\n      \"evidence\": \"MYR1 knockout epistasis, IP from infected host cells, ectopic expression in Neospora caninum and uninfected HFFs, and loss-of-function growth assay\",\n      \"pmids\": [\"31040242\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the TEEGR-E2F3/E2F4/DP1 interaction unknown\", \"How cyclin E upregulation causally supports parasite growth not dissected\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Resolved which host cell cycle events depend on TEEGR versus host context, attributing the G1-to-S transition to TEEGR but the subsequent S-phase block to host cell type and contact inhibition.\",\n      \"evidence\": \"FUCCI live-cell cell cycle reporter with TEEGR knockout parasites across multiple host cell lines\",\n      \"pmids\": [\"35587658\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the host-context-dependent S-phase block unidentified\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Positioned TEEGR as a counter-regulator of GRA15/GRA24-driven macrophage chemotaxis, showing it opposes NF-\\u03baB-induced CCR7-mediated hypermigration.\",\n      \"evidence\": \"Individual effector knockouts, macrophage chemotaxis/migration assays, and NF-\\u03baB readouts\",\n      \"pmids\": [\"39207098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TEEGR acts directly on the CCR7 axis or via its transcriptional/EZH2 activity not distinguished\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Separated TEEGR's cyclin E function from early infection-induced DNA damage, establishing that MYR1-dependent export causes S-phase arrest and DNA double-strand breaks but that TEEGR/cyclin E1 upregulation is not the mechanism.\",\n      \"evidence\": \"Tg\\u0394myr1 and Tg\\u0394hce1 knockouts, flow cytometry cell cycle analysis, \\u03b3H2AX foci imaging, kinetic time-course\",\n      \"pmids\": [\"39681694\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The MYR1-dependent effector(s) responsible for early DNA damage remain unidentified\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Extended TEEGR's immune-suppressive role to CNS dissemination, showing it suppresses GRA15-driven NF-\\u03baB-dependent CCL5 induction via the MYR translocon in brain endothelial cells and dendritic cells.\",\n      \"evidence\": \"GRA15 and TEEGR knockouts, MYR-translocon dependency assay, CCL5 secretion measurement, NF-\\u03baB readouts in primary brain endothelial cells and DCs\",\n      \"pmids\": [\"41528135\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo relevance to CNS dissemination not directly tested\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Placed TEEGR within a cooperative effector network activating non-canonical NF-\\u03baB, showing it acts additively with seven other MYR1-dependent effectors rather than alone.\",\n      \"evidence\": \"Combinatorial effector knockout panel, RelB/p52 nuclear accumulation assays, TRAF3/NIK western blotting, MYR1-dependency epistasis\",\n      \"pmids\": [\"42663465\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The specific molecular contribution of TEEGR to TRAF3 depletion/NIK stabilization not isolated\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TEEGR simultaneously reconciles its transcriptional activation of E2F/cyclin E with its NF-\\u03baB-suppressive and EZH2-inducing activities at the molecular level remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of TEEGR or its host complexes\", \"Direct EZH2-recruitment mechanism unknown\", \"Domain-level separation of transcriptional versus immune-modulatory functions untested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003712\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0008134\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0020003\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000082\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0043124\", \"supporting_discovery_ids\": [0, 3, 5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0038061\", \"supporting_discovery_ids\": [6], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Host cyclin E regulatory complex (E2F3/E2F4/DP1)\"\n    ],\n    \"partners\": [\n      \"E2F3 (host)\",\n      \"E2F4 (host)\",\n      \"DP1 (host)\",\n      \"MYR1 (parasite translocon, required for export)\",\n      \"EZH2 (host, upregulated)\"\n    ],\n    \"other_free_text\": [\n      \"Exported via the MYR1/MYR translocon from the parasitophorous vacuole into the host nucleus [#1, #5]\",\n      \"Necessary and sufficient for cyclin E/E2F target gene upregulation; loss causes parasite growth defect [#1]\",\n      \"Counter-regulates GRA15-driven NF-\\u03baB outputs including CCR7-mediated macrophage hypermigration and CCL5/CCR5-axis-driven CNS dissemination [#3, #5]\",\n      \"Acts additively with seven other MYR1-dependent effectors in non-canonical NF-\\u03baB (RelB/p52) activation; not solely responsible [#6]\",\n      \"Not responsible for early MYR1-dependent S-phase arrest/DNA double-strand break induction [#4]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_239010","name":"TEEGR","product":"E2F4-associated EZH2-inducing gene regulator TEEGR","uniprot_acc":"S8F4W1","chromosome":"TGME49_chrVI","start_pos":390904},{"strain":"GT1","gene_id":"TGGT1_239010","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":386043},{"strain":"VEG","gene_id":"TGVEG_239010","name":null,"product":"putative transmembrane protein","uniprot_acc":"V4ZG39","chromosome":"TGVEG_chrVI","start_pos":405435}]}