{"gene":"TG_293900","gene_symbol":"SPATR","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2014,"finding":"TgSPATR is a micronemal protein required for efficient host cell invasion; genetic ablation (Δspatr) reduced invasion by ~50% compared to parental strains, a defect reversed by genetic complementation, establishing a direct role for TgSPATR in invasion.","method":"Gene knockout (Δspatr) and genetic complementation with invasion assays","journal":"Infection and immunity","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean KO with defined invasion phenotype, fully reversed by complementation, single lab but two orthogonal genetic approaches","pmids":["25092910"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"Δspatr parasites are significantly attenuated in mouse virulence (~20% of mice survived infection), demonstrating that TgSPATR contributes to in vivo pathogenesis.","method":"Mouse virulence assay with Δspatr and parental strains","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined in vivo phenotype, single lab, single method","pmids":["25092910"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"The Plasmodium falciparum SPATR ortholog (PfSPATR) localizes correctly to micronemes when expressed in T. gondii Δspatr parasites but fails to rescue the invasion defect due to an apparent secretion failure, indicating species-specific functional divergence in secretion.","method":"Heterologous complementation with PfSPATR in Δspatr parasites, localization imaging and invasion assays","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — complementation with localization imaging and functional invasion readout, single lab","pmids":["25092910"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"SPATR forms a distinct protein complex with the microneme proteins CLAMP and CLIP (CLAMP-linked invasion protein); this complex mediates rhoptry discharge following host-cell contact, and knockdown of any member of the complex impairs rhoptry discharge.","method":"Co-immunoprecipitation/complex identification, knockdown of complex members with rhoptry discharge assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal complex identification combined with functional knockdown of each member showing rhoptry discharge defect, single lab but multiple orthogonal methods","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"SPATR acts as an accessory factor within the CLAMP–CLIP–SPATR complex in Toxoplasma (complex essential for rhoptry discharge), whereas CLAMP and CLIP are the core essential components conserved ubiquitously across apicomplexans.","method":"Phylogenetic analysis combined with genetic knockdown and functional invasion/rhoptry discharge assays","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional knockdown data combined with phylogenetic analysis, single lab, accessory vs. core role inferred from comparative genetics","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgSPATR is a microneme protein that forms a trimeric complex with CLAMP and CLIP; this complex is required for rhoptry discharge upon host-cell contact, and loss of TgSPATR reduces invasion by ~50% and attenuates virulence in vivo, with SPATR serving as an accessory rather than core essential subunit of the complex."},"narrative":{"mechanistic_narrative":"SPATR is a secreted micronemal protein of apicomplexan parasites that promotes host-cell invasion by enabling rhoptry discharge upon contact with the host cell [PMID:25092910, PMID:37886905]. In Toxoplasma gondii, SPATR assembles into a trimeric microneme complex with CLAMP and CLIP, and knockdown of any complex member impairs rhoptry discharge; within this complex SPATR functions as an accessory subunit while CLAMP and CLIP constitute the core, phylogenetically conserved essential components [PMID:37886905]. Genetic ablation of TgSPATR reduces host-cell invasion by roughly half, a defect reversed by complementation, and attenuates virulence in mice [PMID:25092910]. The pathway is species-divergent at the level of secretion: the Plasmodium falciparum ortholog traffics correctly to Toxoplasma micronemes but fails to be secreted and cannot rescue the invasion defect [PMID:25092910]. Beyond its role in this complex and in rhoptry discharge, the molecular activity of SPATR has not been further characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing whether SPATR has a direct functional role in the parasite, knockout defined it as a micronemal protein required for efficient host-cell invasion.","evidence":"Gene knockout (Δspatr) with genetic complementation and invasion assays in T. gondii","pmids":["25092910"],"confidence":"High","gaps":["The molecular step of invasion affected was not resolved in this study","No binding partners or biochemical activity identified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"claim":"To test in vivo relevance, virulence assays showed Δspatr parasites are attenuated, linking SPATR to pathogenesis beyond the cell-culture invasion phenotype.","evidence":"Mouse virulence assay comparing Δspatr and parental strains","pmids":["25092910"],"confidence":"Medium","gaps":["Single method, single lab","Mechanistic basis of attenuation not dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"claim":"Cross-species complementation asked whether SPATR function is conserved; the P. falciparum ortholog localized correctly but failed to be secreted and did not rescue invasion, revealing species-specific divergence in secretion.","evidence":"Heterologous complementation with PfSPATR in Δspatr parasites, localization imaging and invasion assays","pmids":["25092910"],"confidence":"Medium","gaps":["The determinants of the secretion failure were not identified","Whether PfSPATR functions natively in Plasmodium invasion was not tested here"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"To place SPATR in a pathway, complex identification and functional knockdown showed SPATR forms a complex with CLAMP and CLIP that mediates rhoptry discharge after host-cell contact, defining the molecular event it controls.","evidence":"Co-immunoprecipitation/complex identification plus knockdown of each member with rhoptry discharge assays in T. gondii","pmids":["37886905"],"confidence":"High","gaps":["How the complex triggers rhoptry discharge mechanistically is unresolved","The direct interaction interfaces among SPATR, CLAMP, and CLIP were not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Comparative genetics distinguished essential from accessory roles, defining SPATR as an accessory subunit while CLAMP and CLIP are the conserved core of the complex across apicomplexans.","evidence":"Phylogenetic analysis combined with genetic knockdown and functional invasion/rhoptry discharge assays","pmids":["37886905"],"confidence":"Medium","gaps":["The accessory vs. core distinction is inferred from comparative genetics rather than direct structural data","The specific contribution of SPATR to complex stability or function was not isolated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How the SPATR-CLAMP-CLIP complex senses host-cell contact and mechanistically triggers rhoptry discharge, and what biochemical activity SPATR itself contributes, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the complex","No defined molecular activity for SPATR","Signal transduction from contact to discharge unmapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SPATR-CLAMP-CLIP microneme complex"],"partners":["CLAMP","CLIP"],"other_free_text":["Micronemal protein required for efficient host-cell invasion in T. gondii; Δspatr reduces invasion ~50% and attenuates mouse virulence [#0, #1]","Complex mediates rhoptry discharge upon host-cell contact; SPATR is an accessory subunit while CLAMP and CLIP are the conserved core [#3, #4]","P. falciparum SPATR ortholog localizes to T. gondii micronemes but fails to be secreted and does not rescue invasion, indicating species-specific secretion divergence [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25092910","id":"PMC_25092910","title":"A conserved apicomplexan microneme protein contributes to Toxoplasma gondii invasion and virulence.","date":"2014","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/25092910","citation_count":34,"is_preprint":false},{"pmid":"37886905","id":"PMC_37886905","title":"A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.","date":"2023","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/37886905","citation_count":21,"is_preprint":false},{"pmid":"41532258","id":"PMC_41532258","title":"Is Toxoplasma gondii-secreted Protein With an Altered Thrombospondin Repeat (TgSPATR) a Potential Candidate for Immunisation? An Immunoinformatics-Based Analysis.","date":"2026","source":"Veterinary medicine and science","url":"https://pubmed.ncbi.nlm.nih.gov/41532258","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4069,"output_tokens":1185,"usd":0.014991,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6208,"output_tokens":2276,"usd":0.04397,"stage2_stop_reason":"end_turn"},"total_usd":0.058961,"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\": 2014,\n      \"finding\": \"TgSPATR is a micronemal protein required for efficient host cell invasion; genetic ablation (Δspatr) reduced invasion by ~50% compared to parental strains, a defect reversed by genetic complementation, establishing a direct role for TgSPATR in invasion.\",\n      \"method\": \"Gene knockout (Δspatr) and genetic complementation with invasion assays\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined invasion phenotype, fully reversed by complementation, single lab but two orthogonal genetic approaches\",\n      \"pmids\": [\"25092910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Δspatr parasites are significantly attenuated in mouse virulence (~20% of mice survived infection), demonstrating that TgSPATR contributes to in vivo pathogenesis.\",\n      \"method\": \"Mouse virulence assay with Δspatr and parental strains\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined in vivo phenotype, single lab, single method\",\n      \"pmids\": [\"25092910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The Plasmodium falciparum SPATR ortholog (PfSPATR) localizes correctly to micronemes when expressed in T. gondii Δspatr parasites but fails to rescue the invasion defect due to an apparent secretion failure, indicating species-specific functional divergence in secretion.\",\n      \"method\": \"Heterologous complementation with PfSPATR in Δspatr parasites, localization imaging and invasion assays\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — complementation with localization imaging and functional invasion readout, single lab\",\n      \"pmids\": [\"25092910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SPATR forms a distinct protein complex with the microneme proteins CLAMP and CLIP (CLAMP-linked invasion protein); this complex mediates rhoptry discharge following host-cell contact, and knockdown of any member of the complex impairs rhoptry discharge.\",\n      \"method\": \"Co-immunoprecipitation/complex identification, knockdown of complex members with rhoptry discharge assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex identification combined with functional knockdown of each member showing rhoptry discharge defect, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SPATR acts as an accessory factor within the CLAMP–CLIP–SPATR complex in Toxoplasma (complex essential for rhoptry discharge), whereas CLAMP and CLIP are the core essential components conserved ubiquitously across apicomplexans.\",\n      \"method\": \"Phylogenetic analysis combined with genetic knockdown and functional invasion/rhoptry discharge assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional knockdown data combined with phylogenetic analysis, single lab, accessory vs. core role inferred from comparative genetics\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgSPATR is a microneme protein that forms a trimeric complex with CLAMP and CLIP; this complex is required for rhoptry discharge upon host-cell contact, and loss of TgSPATR reduces invasion by ~50% and attenuates virulence in vivo, with SPATR serving as an accessory rather than core essential subunit of the complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPATR is a secreted micronemal protein of apicomplexan parasites that promotes host-cell invasion by enabling rhoptry discharge upon contact with the host cell [#0, #3]. In Toxoplasma gondii, SPATR assembles into a trimeric microneme complex with CLAMP and CLIP, and knockdown of any complex member impairs rhoptry discharge; within this complex SPATR functions as an accessory subunit while CLAMP and CLIP constitute the core, phylogenetically conserved essential components [#3, #4]. Genetic ablation of TgSPATR reduces host-cell invasion by roughly half, a defect reversed by complementation, and attenuates virulence in mice [#0, #1]. The pathway is species-divergent at the level of secretion: the Plasmodium falciparum ortholog traffics correctly to Toxoplasma micronemes but fails to be secreted and cannot rescue the invasion defect [#2]. Beyond its role in this complex and in rhoptry discharge, the molecular activity of SPATR has not been further characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether SPATR has a direct functional role in the parasite, knockout defined it as a micronemal protein required for efficient host-cell invasion.\",\n      \"evidence\": \"Gene knockout (\\u0394spatr) with genetic complementation and invasion assays in T. gondii\",\n      \"pmids\": [\"25092910\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The molecular step of invasion affected was not resolved in this study\", \"No binding partners or biochemical activity identified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To test in vivo relevance, virulence assays showed \\u0394spatr parasites are attenuated, linking SPATR to pathogenesis beyond the cell-culture invasion phenotype.\",\n      \"evidence\": \"Mouse virulence assay comparing \\u0394spatr and parental strains\",\n      \"pmids\": [\"25092910\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method, single lab\", \"Mechanistic basis of attenuation not dissected\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Cross-species complementation asked whether SPATR function is conserved; the P. falciparum ortholog localized correctly but failed to be secreted and did not rescue invasion, revealing species-specific divergence in secretion.\",\n      \"evidence\": \"Heterologous complementation with PfSPATR in \\u0394spatr parasites, localization imaging and invasion assays\",\n      \"pmids\": [\"25092910\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The determinants of the secretion failure were not identified\", \"Whether PfSPATR functions natively in Plasmodium invasion was not tested here\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To place SPATR in a pathway, complex identification and functional knockdown showed SPATR forms a complex with CLAMP and CLIP that mediates rhoptry discharge after host-cell contact, defining the molecular event it controls.\",\n      \"evidence\": \"Co-immunoprecipitation/complex identification plus knockdown of each member with rhoptry discharge assays in T. gondii\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the complex triggers rhoptry discharge mechanistically is unresolved\", \"The direct interaction interfaces among SPATR, CLAMP, and CLIP were not mapped\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Comparative genetics distinguished essential from accessory roles, defining SPATR as an accessory subunit while CLAMP and CLIP are the conserved core of the complex across apicomplexans.\",\n      \"evidence\": \"Phylogenetic analysis combined with genetic knockdown and functional invasion/rhoptry discharge assays\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The accessory vs. core distinction is inferred from comparative genetics rather than direct structural data\", \"The specific contribution of SPATR to complex stability or function was not isolated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the SPATR-CLAMP-CLIP complex senses host-cell contact and mechanistically triggers rhoptry discharge, and what biochemical activity SPATR itself contributes, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the complex\", \"No defined molecular activity for SPATR\", \"Signal transduction from contact to discharge unmapped\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"SPATR-CLAMP-CLIP microneme complex\"],\n    \"partners\": [\"CLAMP\", \"CLIP\"],\n    \"other_free_text\": [\n      \"Micronemal protein required for efficient host-cell invasion in T. gondii; \\u0394spatr reduces invasion ~50% and attenuates mouse virulence [#0, #1]\",\n      \"Complex mediates rhoptry discharge upon host-cell contact; SPATR is an accessory subunit while CLAMP and CLIP are the conserved core [#3, #4]\",\n      \"P. falciparum SPATR ortholog localizes to T. gondii micronemes but fails to be secreted and does not rescue invasion, indicating species-specific secretion divergence [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_293900","name":"SPATR","product":"sporozoite protein with an altered thrombospondin repeat SPATR","uniprot_acc":"A0A125YR89","chromosome":"TGME49_chrIa","start_pos":633453},{"strain":"GT1","gene_id":"TGGT1_293900","name":null,"product":"sporozoite protein with an altered thrombospondin repeat SPATR","uniprot_acc":null,"chromosome":"TGGT1_chrIa","start_pos":619649},{"strain":"RH88","gene_id":"TGRH88_019180","name":null,"product":"sporozoite protein with an altered thrombospondin repeat SPATR","uniprot_acc":null,"chromosome":"CM023081","start_pos":639816},{"strain":"VEG","gene_id":"TGVEG_293900","name":null,"product":"sporozoite protein with an altered thrombospondin repeat SPATR","uniprot_acc":"B9PY79","chromosome":"TGVEG_chrIa","start_pos":643265}]}