{"gene":"PF3D7_0212600","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2003,"finding":"SPATR (PF3D7_0212600) is expressed on the surface of P. falciparum sporozoites and around the rhoptries in asexual erythrocytic stages, as determined by immunoelectron microscopy.","method":"Immunoelectron microscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunoelectron microscopy with functional stage context, single lab","pmids":["12716913"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"Recombinant SPATR (PF3D7_0212600) produced in E. coli binds to HepG2 hepatoma cells in a dose-dependent manner, suggesting it acts as a parasite ligand for hepatocyte invasion.","method":"Cell-binding assay with recombinant protein","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding assay with dose-dependence, single lab","pmids":["12716913"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"Antibodies raised against SPATR (PF3D7_0212600) block invasion of sporozoites into a transformed hepatoma cell line, establishing a functional role in hepatocyte invasion.","method":"Invasion inhibition assay using anti-SPATR antibodies","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional inhibition assay with antibodies, single lab","pmids":["12716913"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"Synthetic peptides derived from SPATR (PF3D7_0212600) include four high-activity binding peptides (HABPs) to human red blood cells and two to HepG2 hepatoma cells; one peptide (32686) binds both cell types. All HABPs inhibited in vitro merozoite invasion at 200 µM and binding was saturable and differentially affected by enzymatic treatment of target cells.","method":"Synthetic peptide binding assays with RBCs and HepG2 cells; in vitro invasion inhibition assay; circular dichroism","journal":"Biochimie","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal binding and inhibition assays, single lab","pmids":["18832006"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"In P. berghei, SPATR is essential for blood stage parasite growth: conditional knockdown/knockout mutants show that SPATR is dispensable for sporozoite motility, hepatocyte invasion, liver stage development, and merosome formation, but hepatic merozoites lacking SPATR fail to establish blood stage infection in vivo.","method":"Conditional mutagenesis (DiCre system) in P. berghei; in vivo mouse infection assays; sporozoite motility and hepatocyte invasion assays","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional genetic knockdown with specific phenotypic readout at each life cycle stage, multiple assays in a single study","pmids":["31755154"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"In Toxoplasma gondii, SPATR forms a distinct microneme protein complex with CLAMP and CLIP; knockdown of SPATR (as a member of this complex) impairs rhoptry discharge following host-cell contact. Orthologs of this complex exist in P. falciparum, and SPATR is described as essential for P. falciparum blood stage invasion.","method":"Co-immunoprecipitation/complex identification; conditional knockdown; rhoptry discharge assay; phylogenetic analysis","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complex membership established by Co-IP and functional knockdown in T. gondii; P. falciparum essentiality stated but primary experiments in T. gondii","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"When P. falciparum SPATR (PF3D7_0212600) was expressed in T. gondii Δspatr parasites, it localized correctly to micronemes but failed to reverse the invasion deficiency, apparently due to a failure in secretion, indicating that PfSPATR cannot functionally substitute for TgSPATR despite correct organellar targeting.","method":"Genetic complementation of T. gondii Δspatr with PfSPATR; immunofluorescence localization; invasion assays","journal":"Infection and immunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genetic complementation experiment with localization and functional readout, single lab","pmids":["25092910"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"In P. berghei, SPATR is expressed in sporozoites and its downregulation impacts sporozoite infectivity, consistent with participation in the conserved CLAMP-CLIP-SPATR microneme complex that mediates host cell invasion across invasive zoite stages.","method":"CRISPR-assisted conditional genome editing (dimerisable Cre); sporozoite infectivity assays; genetic epistasis with CLIP and CLAMP","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional genetics in P. berghei with specific phenotypic readouts; preprint, single lab","pmids":["41929181"],"is_preprint":true,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"SPATR (PF3D7_0212600) is a multistage surface/micronemal protein that localizes to the sporozoite surface and around rhoptries in asexual erythrocytic stages; it binds hepatocytes and red blood cells via specific peptide sequences to facilitate invasion, is dispensable for hepatocyte invasion but essential for blood-stage establishment in P. berghei, and participates as an accessory component of a conserved microneme complex (CLAMP-CLIP-SPATR) that mediates rhoptry discharge upon host-cell contact."},"narrative":{"mechanistic_narrative":"SPATR (PF3D7_0212600) is a multistage secreted invasion-associated protein of Plasmodium that acts as a parasite ligand for host-cell attachment and contributes to host-cell invasion across life-cycle stages [PMID:12716913]. In P. falciparum it is displayed on the sporozoite surface and localizes around the rhoptries in asexual erythrocytic stages [PMID:12716913]. Recombinant SPATR binds HepG2 hepatoma cells dose-dependently, and anti-SPATR antibodies block sporozoite invasion of hepatoma cells, establishing a functional role in hepatocyte invasion [PMID:12716913]; the binding activity maps to discrete high-activity binding peptides that engage both red blood cells and hepatocytes and that inhibit merozoite invasion in vitro [PMID:18832006]. Genetic dissection in P. berghei shows SPATR is dispensable for sporozoite motility, hepatocyte invasion, and liver-stage development but is required for hepatic merozoites to establish blood-stage infection, and its downregulation reduces sporozoite infectivity [PMID:31755154, PMID:41929181]. Beyond its ligand activity, SPATR is an accessory member of a conserved microneme complex with CLAMP and CLIP; in Toxoplasma gondii this complex is required for rhoptry discharge upon host-cell contact, and orthologs exist in P. falciparum [PMID:37886905]. P. falciparum SPATR targets micronemes correctly when expressed in T. gondii but fails to rescue the invasion deficiency of T. gondii Δspatr parasites, indicating the two orthologs are not functionally interchangeable [PMID:25092910].","teleology":[{"year":2003,"claim":"Establishing where SPATR resides and whether it engages host cells was the first step in defining it as an invasion ligand rather than an internal parasite protein.","evidence":"Immunoelectron microscopy plus recombinant-protein cell-binding and antibody invasion-inhibition assays in P. falciparum","pmids":["12716913"],"confidence":"Medium","gaps":["Host receptor on hepatocytes not identified","Binding shown for recombinant protein, not native parasite protein in context","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"Mapping the binding activity to defined peptides addressed which regions of SPATR mediate host-cell engagement and whether the same protein contributes to both hepatocyte and erythrocyte invasion.","evidence":"Synthetic peptide binding assays against RBCs and HepG2 cells, in vitro merozoite invasion inhibition, and circular dichroism in P. falciparum","pmids":["18832006"],"confidence":"Medium","gaps":["Peptide-level binding does not establish the receptor identity","Physiological relevance of 200 µM inhibition unclear","No structural model of the intact protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Cross-species complementation tested whether the Plasmodium and Toxoplasma orthologs share a conserved function, revealing that correct organellar targeting is not sufficient for functional substitution.","evidence":"Genetic complementation of T. gondii Δspatr with P. falciparum SPATR, with immunofluorescence localization and invasion assays","pmids":["25092910"],"confidence":"Medium","gaps":["Molecular basis of the secretion failure not defined","Does not resolve the native P. falciparum function directly","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Conditional genetics resolved at which life-cycle stage SPATR is actually required, separating a dispensable role in liver-stage invasion from an essential role in blood-stage establishment.","evidence":"DiCre conditional knockdown/knockout in P. berghei with stage-specific motility, invasion, and in vivo mouse infection assays","pmids":["31755154"],"confidence":"High","gaps":["Molecular step at which blood-stage establishment fails not defined","Whether the P. falciparum ortholog behaves identically not directly tested here"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Complex identification placed SPATR within a defined molecular machine, showing it acts as a member of a CLAMP-CLIP-SPATR microneme complex linked to rhoptry discharge.","evidence":"Co-immunoprecipitation/complex identification, conditional knockdown, rhoptry discharge assay, and phylogenetics, primary experiments in T. gondii with stated P. falciparum orthology","pmids":["37886905"],"confidence":"Medium","gaps":["Rhoptry-discharge role demonstrated in T. gondii, not directly in P. falciparum","SPATR's specific contribution within the complex versus CLAMP/CLIP not dissected","How host-cell contact is transduced to discharge unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Sporozoite-stage conditional genetics and epistasis extended the complex model into Plasmodium, linking SPATR downregulation to reduced sporozoite infectivity alongside CLIP and CLAMP.","evidence":"CRISPR-assisted dimerisable-Cre conditional editing, sporozoite infectivity assays, and genetic epistasis with CLIP and CLAMP in P. berghei (preprint)","pmids":["41929181"],"confidence":"Medium","gaps":["Preprint, single lab","Direct biochemical demonstration of the complex in Plasmodium not shown","Mechanism connecting the complex to sporozoite infectivity not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The host receptor(s) engaged by SPATR and the precise molecular step by which it enables blood-stage establishment and rhoptry discharge in Plasmodium remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No identified host receptor for SPATR","Rhoptry-discharge role not shown directly in P. falciparum","Structure and stoichiometry of the CLAMP-CLIP-SPATR complex in Plasmodium undefined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CLAMP-CLIP-SPATR microneme complex [#5, #7]"],"partners":["CLAMP [#5, #7]","CLIP [#5, #7]"],"other_free_text":["In P. falciparum, SPATR is displayed on the sporozoite surface and localizes around rhoptries in asexual erythrocytic stages [#0].","Discrete high-activity binding peptides mediate binding to both human red blood cells and HepG2 hepatocytes; one peptide binds both [#3].","In P. berghei, SPATR is dispensable for sporozoite motility, hepatocyte invasion, and liver-stage development but essential for hepatic merozoites to establish blood-stage infection [#4].","P. falciparum SPATR targets micronemes correctly in T. gondii Δspatr but fails to rescue invasion, apparently due to a secretion failure, indicating orthologs are not functionally interchangeable [#6]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"17041140","id":"PMC_17041140","title":"Developmental biology of sporozoite-host interactions in Plasmodium falciparum malaria: implications for vaccine design.","date":"2006","source":"Clinical microbiology reviews","url":"https://pubmed.ncbi.nlm.nih.gov/17041140","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12716913","id":"PMC_12716913","title":"PfSPATR, a Plasmodium falciparum protein containing an altered thrombospondin type I repeat domain is expressed at several stages of the parasite life cycle and is the target of inhibitory antibodies.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12716913","citation_count":48,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"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":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"31755154","id":"PMC_31755154","title":"Secreted protein with altered thrombospondin repeat (SPATR) is essential for asexual blood stages but not required for hepatocyte invasion by the malaria parasite Plasmodium berghei.","date":"2019","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31755154","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16113256","id":"PMC_16113256","title":"Identification, cloning, expression, and characterization of the gene for Plasmodium knowlesi surface protein containing an altered thrombospondin repeat domain.","date":"2005","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/16113256","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35594144","id":"PMC_35594144","title":"C-Mannosyltransferase Is Essential for Malaria Transmission in Plasmodium berghei.","date":"2022","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/35594144","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23734702","id":"PMC_23734702","title":"Cloning, expression, and immunocharacterization of surface protein containing an altered thrombospondin repeat domain (SPATR) from Plasmodium knowlesi.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/23734702","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18832006","id":"PMC_18832006","title":"Identification of peptides with high red blood cell and hepatocyte binding activity in the Plasmodium falciparum multi-stage invasion proteins: PfSPATR and MCP-1.","date":"2008","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/18832006","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34252120","id":"PMC_34252120","title":"Screening of viral-vectored P. falciparum pre-erythrocytic candidate vaccine antigens using chimeric rodent parasites.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/34252120","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36602208","id":"PMC_36602208","title":"Genetic diversity of secreted protein with an altered thrombospondin repeat (SPATR) of Plasmodium knowlesi clinical isolates from Malaysia.","date":"2022","source":"Tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/36602208","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39154272","id":"PMC_39154272","title":"Inhibition of Plasmodium knowlesi merozoite invasion into human erythrocytes by antibodies raised against the parasite's secreted protein with altered thrombospondin repeat (SPATR).","date":"2024","source":"Tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/39154272","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41929181","id":"PMC_41929181","title":"The CLAMP-Linked Invasion Protein (CLIP) plays an essential role in Plasmodium berghei zoites.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41929181","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPATR"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9092,"output_tokens":1977,"usd":0.028466,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7234,"output_tokens":3260,"usd":0.058835,"stage2_stop_reason":"end_turn"},"total_usd":0.087301,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"SPATR (PF3D7_0212600) is expressed on the surface of P. falciparum sporozoites and around the rhoptries in asexual erythrocytic stages, as determined by immunoelectron microscopy.\",\n      \"method\": \"Immunoelectron microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunoelectron microscopy with functional stage context, single lab\",\n      \"pmids\": [\"12716913\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Recombinant SPATR (PF3D7_0212600) produced in E. coli binds to HepG2 hepatoma cells in a dose-dependent manner, suggesting it acts as a parasite ligand for hepatocyte invasion.\",\n      \"method\": \"Cell-binding assay with recombinant protein\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding assay with dose-dependence, single lab\",\n      \"pmids\": [\"12716913\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Antibodies raised against SPATR (PF3D7_0212600) block invasion of sporozoites into a transformed hepatoma cell line, establishing a functional role in hepatocyte invasion.\",\n      \"method\": \"Invasion inhibition assay using anti-SPATR antibodies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional inhibition assay with antibodies, single lab\",\n      \"pmids\": [\"12716913\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Synthetic peptides derived from SPATR (PF3D7_0212600) include four high-activity binding peptides (HABPs) to human red blood cells and two to HepG2 hepatoma cells; one peptide (32686) binds both cell types. All HABPs inhibited in vitro merozoite invasion at 200 µM and binding was saturable and differentially affected by enzymatic treatment of target cells.\",\n      \"method\": \"Synthetic peptide binding assays with RBCs and HepG2 cells; in vitro invasion inhibition assay; circular dichroism\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal binding and inhibition assays, single lab\",\n      \"pmids\": [\"18832006\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In P. berghei, SPATR is essential for blood stage parasite growth: conditional knockdown/knockout mutants show that SPATR is dispensable for sporozoite motility, hepatocyte invasion, liver stage development, and merosome formation, but hepatic merozoites lacking SPATR fail to establish blood stage infection in vivo.\",\n      \"method\": \"Conditional mutagenesis (DiCre system) in P. berghei; in vivo mouse infection assays; sporozoite motility and hepatocyte invasion assays\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional genetic knockdown with specific phenotypic readout at each life cycle stage, multiple assays in a single study\",\n      \"pmids\": [\"31755154\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In Toxoplasma gondii, SPATR forms a distinct microneme protein complex with CLAMP and CLIP; knockdown of SPATR (as a member of this complex) impairs rhoptry discharge following host-cell contact. Orthologs of this complex exist in P. falciparum, and SPATR is described as essential for P. falciparum blood stage invasion.\",\n      \"method\": \"Co-immunoprecipitation/complex identification; conditional knockdown; rhoptry discharge assay; phylogenetic analysis\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complex membership established by Co-IP and functional knockdown in T. gondii; P. falciparum essentiality stated but primary experiments in T. gondii\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"When P. falciparum SPATR (PF3D7_0212600) was expressed in T. gondii Δspatr parasites, it localized correctly to micronemes but failed to reverse the invasion deficiency, apparently due to a failure in secretion, indicating that PfSPATR cannot functionally substitute for TgSPATR despite correct organellar targeting.\",\n      \"method\": \"Genetic complementation of T. gondii Δspatr with PfSPATR; immunofluorescence localization; invasion assays\",\n      \"journal\": \"Infection and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genetic complementation experiment with localization and functional readout, single lab\",\n      \"pmids\": [\"25092910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In P. berghei, SPATR is expressed in sporozoites and its downregulation impacts sporozoite infectivity, consistent with participation in the conserved CLAMP-CLIP-SPATR microneme complex that mediates host cell invasion across invasive zoite stages.\",\n      \"method\": \"CRISPR-assisted conditional genome editing (dimerisable Cre); sporozoite infectivity assays; genetic epistasis with CLIP and CLAMP\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional genetics in P. berghei with specific phenotypic readouts; preprint, single lab\",\n      \"pmids\": [\"41929181\"],\n      \"is_preprint\": true,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"SPATR (PF3D7_0212600) is a multistage surface/micronemal protein that localizes to the sporozoite surface and around rhoptries in asexual erythrocytic stages; it binds hepatocytes and red blood cells via specific peptide sequences to facilitate invasion, is dispensable for hepatocyte invasion but essential for blood-stage establishment in P. berghei, and participates as an accessory component of a conserved microneme complex (CLAMP-CLIP-SPATR) that mediates rhoptry discharge upon host-cell contact.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPATR (PF3D7_0212600) is a multistage secreted invasion-associated protein of Plasmodium that acts as a parasite ligand for host-cell attachment and contributes to host-cell invasion across life-cycle stages [#0, #1]. In P. falciparum it is displayed on the sporozoite surface and localizes around the rhoptries in asexual erythrocytic stages [#0]. Recombinant SPATR binds HepG2 hepatoma cells dose-dependently, and anti-SPATR antibodies block sporozoite invasion of hepatoma cells, establishing a functional role in hepatocyte invasion [#1, #2]; the binding activity maps to discrete high-activity binding peptides that engage both red blood cells and hepatocytes and that inhibit merozoite invasion in vitro [#3]. Genetic dissection in P. berghei shows SPATR is dispensable for sporozoite motility, hepatocyte invasion, and liver-stage development but is required for hepatic merozoites to establish blood-stage infection, and its downregulation reduces sporozoite infectivity [#4, #7]. Beyond its ligand activity, SPATR is an accessory member of a conserved microneme complex with CLAMP and CLIP; in Toxoplasma gondii this complex is required for rhoptry discharge upon host-cell contact, and orthologs exist in P. falciparum [#5]. P. falciparum SPATR targets micronemes correctly when expressed in T. gondii but fails to rescue the invasion deficiency of T. gondii Δspatr parasites, indicating the two orthologs are not functionally interchangeable [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing where SPATR resides and whether it engages host cells was the first step in defining it as an invasion ligand rather than an internal parasite protein.\",\n      \"evidence\": \"Immunoelectron microscopy plus recombinant-protein cell-binding and antibody invasion-inhibition assays in P. falciparum\",\n      \"pmids\": [\"12716913\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Host receptor on hepatocytes not identified\",\n        \"Binding shown for recombinant protein, not native parasite protein in context\",\n        \"Single lab\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Mapping the binding activity to defined peptides addressed which regions of SPATR mediate host-cell engagement and whether the same protein contributes to both hepatocyte and erythrocyte invasion.\",\n      \"evidence\": \"Synthetic peptide binding assays against RBCs and HepG2 cells, in vitro merozoite invasion inhibition, and circular dichroism in P. falciparum\",\n      \"pmids\": [\"18832006\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Peptide-level binding does not establish the receptor identity\",\n        \"Physiological relevance of 200 µM inhibition unclear\",\n        \"No structural model of the intact protein\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Cross-species complementation tested whether the Plasmodium and Toxoplasma orthologs share a conserved function, revealing that correct organellar targeting is not sufficient for functional substitution.\",\n      \"evidence\": \"Genetic complementation of T. gondii Δspatr with P. falciparum SPATR, with immunofluorescence localization and invasion assays\",\n      \"pmids\": [\"25092910\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Molecular basis of the secretion failure not defined\",\n        \"Does not resolve the native P. falciparum function directly\",\n        \"Single lab\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Conditional genetics resolved at which life-cycle stage SPATR is actually required, separating a dispensable role in liver-stage invasion from an essential role in blood-stage establishment.\",\n      \"evidence\": \"DiCre conditional knockdown/knockout in P. berghei with stage-specific motility, invasion, and in vivo mouse infection assays\",\n      \"pmids\": [\"31755154\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Molecular step at which blood-stage establishment fails not defined\",\n        \"Whether the P. falciparum ortholog behaves identically not directly tested here\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Complex identification placed SPATR within a defined molecular machine, showing it acts as a member of a CLAMP-CLIP-SPATR microneme complex linked to rhoptry discharge.\",\n      \"evidence\": \"Co-immunoprecipitation/complex identification, conditional knockdown, rhoptry discharge assay, and phylogenetics, primary experiments in T. gondii with stated P. falciparum orthology\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Rhoptry-discharge role demonstrated in T. gondii, not directly in P. falciparum\",\n        \"SPATR's specific contribution within the complex versus CLAMP/CLIP not dissected\",\n        \"How host-cell contact is transduced to discharge unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Sporozoite-stage conditional genetics and epistasis extended the complex model into Plasmodium, linking SPATR downregulation to reduced sporozoite infectivity alongside CLIP and CLAMP.\",\n      \"evidence\": \"CRISPR-assisted dimerisable-Cre conditional editing, sporozoite infectivity assays, and genetic epistasis with CLIP and CLAMP in P. berghei (preprint)\",\n      \"pmids\": [\"41929181\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Preprint, single lab\",\n        \"Direct biochemical demonstration of the complex in Plasmodium not shown\",\n        \"Mechanism connecting the complex to sporozoite infectivity not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The host receptor(s) engaged by SPATR and the precise molecular step by which it enables blood-stage establishment and rhoptry discharge in Plasmodium remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No identified host receptor for SPATR\",\n        \"Rhoptry-discharge role not shown directly in P. falciparum\",\n        \"Structure and stoichiometry of the CLAMP-CLIP-SPATR complex in Plasmodium undefined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0046790\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005102\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [5, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [2, 3, 4]},\n      {\"term_id\": \"GO:0035891\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"CLAMP-CLIP-SPATR microneme complex [#5, #7]\"\n    ],\n    \"partners\": [\n      \"CLAMP [#5, #7]\",\n      \"CLIP [#5, #7]\"\n    ],\n    \"other_free_text\": [\n      \"In P. falciparum, SPATR is displayed on the sporozoite surface and localizes around rhoptries in asexual erythrocytic stages [#0].\",\n      \"Discrete high-activity binding peptides mediate binding to both human red blood cells and HepG2 hepatocytes; one peptide binds both [#3].\",\n      \"In P. berghei, SPATR is dispensable for sporozoite motility, hepatocyte invasion, and liver-stage development but essential for hepatic merozoites to establish blood-stage infection [#4].\",\n      \"P. falciparum SPATR targets micronemes correctly in T. gondii Δspatr but fails to rescue invasion, apparently due to a secretion failure, indicating orthologs are not functionally interchangeable [#6].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0212600","name":null,"product":"secreted protein with altered thrombospondin repeat domain","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0309500","name":null,"product":"secreted protein with altered thrombospondin repeat domain","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0408600","name":null,"product":"secreted protein with altered thrombospondin repeat domain","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SPATR","evaluation":null}