{"gene":"PF3D7_1218000","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2004,"finding":"TRAMP (PF3D7_1218000) localizes to the apical organelles (developing micronemes) of P. falciparum and P. berghei merozoites within intraerythrocytic schizonts, co-localizing with AMA-1, and subsequently relocates onto the merozoite surface prior to or during invasion.","method":"Immunofluorescence localization in intraerythrocytic schizonts of P. falciparum and P. berghei","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunofluorescence replicated in two Plasmodium species in the same study, but no functional consequence explicitly demonstrated","pmids":["15003842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2006,"finding":"TRAMP (PF3D7_1218000) is shed from the merozoite surface by the serine protease PfSUB2 upon invasion of erythrocytes.","method":"Biochemical shedding assay with protease identification","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct identification of the shed protease (PfSUB2), single lab, single study","pmids":["16879884"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Recombinant TRAMP (PF3D7_1218000) extracellular domain does not bind human erythrocytes in an erythrocyte binding assay, and TRAMP-specific antibodies failed to inhibit P. falciparum growth in vitro.","method":"Erythrocyte binding assay with recombinant protein; in vitro growth inhibition assay with antibodies","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct binding and inhibition assays with recombinant protein, single lab; results are negative for erythrocyte binding and invasion inhibition","pmids":["22467743"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"TRAMP (PF3D7_1218000) localizes to the rhoptry bulb (not micronemes) and is secreted during erythrocyte invasion. Both native and recombinant TRAMP bind untreated as well as neuraminidase-, trypsin-, and chymotrypsin-treated human erythrocytes. Release of TRAMP from rhoptries is triggered by adhesion of microneme protein EBA175 to its erythrocyte receptor glycophorin A. Antibodies against TRAMP block erythrocyte invasion, and combination with anti-EBA175 antibodies produces additive inhibition.","method":"Immunofluorescence localization; native and recombinant protein erythrocyte binding assays; invasion inhibition assays with polyclonal antibodies","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (localization, binding assay, inhibition assay) in a single lab; note conflict with 2012 study on erythrocyte binding","pmids":["23387921"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"TRAMP (PF3D7_1218000) forms a complex with PfCSS on the parasite membrane, and together the PfCSS-PfTRAMP complex is bound by the elongated tail of PfRIPR, linking the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) to the merozoite surface. This positions the PfRCR structured core to present PfRH5 and PfCyRPA for interaction with erythrocyte receptors during invasion.","method":"Cryo-electron microscopy structure determination of the PfRCR complex; erythrocyte-binding assay; structural modelling","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure of the complex combined with binding assay and modelling, published in high-impact peer-reviewed journal with multiple orthogonal methods","pmids":["38123677"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"TRAMP (PF3D7_1218000) is a merozoite apical membrane protein that localizes to rhoptries/micronemes and is shed from the merozoite surface by PfSUB2 during erythrocyte invasion; it forms a complex with PfCSS on the parasite membrane, where it anchors the PfRIPR tail and thereby tethers the PfRCR invasion complex (containing PfRH5, PfCyRPA, and PfRIPR) to the merozoite surface to facilitate erythrocyte receptor engagement."},"narrative":{"mechanistic_narrative":"TRAMP (PF3D7_1218000) is a thrombospondin-related apical membrane protein of the Plasmodium merozoite that participates in erythrocyte invasion by tethering the invasion machinery to the parasite surface [PMID:38123677]. It is an apical organelle protein of intraerythrocytic schizont-stage merozoites in both P. falciparum and P. berghei that relocates onto the merozoite surface prior to or during invasion [PMID:15003842], and in P. falciparum it is shed from the surface by the serine protease PfSUB2 during erythrocyte entry [PMID:16879884]. Its secretion from rhoptries is triggered by adhesion of the microneme protein EBA175 to its erythrocyte receptor glycophorin A, and antibodies against TRAMP block invasion, additively with anti-EBA175 antibodies [PMID:23387921]. Structurally, TRAMP forms a complex with PfCSS on the parasite membrane; this PfCSS–PfTRAMP module is engaged by the elongated tail of PfRIPR, thereby linking the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) to the merozoite surface and positioning PfRH5 and PfCyRPA to engage erythrocyte receptors during invasion [PMID:38123677]. Reports of TRAMP's direct erythrocyte-binding activity diverge across studies: recombinant TRAMP failed to bind erythrocytes in one assay [PMID:22467743], whereas native and recombinant TRAMP bound treated and untreated erythrocytes in another [PMID:23387921].","teleology":[{"year":2004,"claim":"Establishing where TRAMP resides and when it becomes accessible was the first step in placing it in the invasion pathway; localization to developing apical organelles with subsequent surface relocation marked it as an invasion-stage protein.","evidence":"Immunofluorescence localization in intraerythrocytic schizonts of P. falciparum and P. berghei, co-localizing with AMA-1","pmids":["15003842"],"confidence":"Medium","gaps":["No functional consequence of localization demonstrated","Whether apical residence is micronemal versus rhoptry was not resolved here (later contested)","Trigger and mechanism of surface relocation not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2006,"claim":"Identifying the protease that removes TRAMP from the merozoite surface connected its dynamics to the regulated proteolytic events of invasion.","evidence":"Biochemical shedding assay with identification of PfSUB2 as the sheddase in P. falciparum","pmids":["16879884"],"confidence":"Medium","gaps":["Single lab, single study","Functional consequence of shedding for invasion not shown","Cleavage site and kinetics not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Testing whether TRAMP is a direct erythrocyte adhesin and a vaccine-relevant invasion target gave negative results, constraining early functional models.","evidence":"Erythrocyte binding assay with recombinant extracellular domain and in vitro growth inhibition assay with TRAMP antibodies","pmids":["22467743"],"confidence":"Medium","gaps":["Negative binding result conflicts with the 2013 study","Recombinant domain may not reproduce native conformation","Antibody epitopes and accessibility not characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Re-examination placed TRAMP in the rhoptry bulb and linked its secretion to EBA175–glycophorin A engagement, arguing for a functional role in invasion supported by antibody inhibition.","evidence":"Immunofluorescence localization, native and recombinant erythrocyte binding assays, and invasion inhibition assays with polyclonal antibodies in P. falciparum","pmids":["23387921"],"confidence":"Medium","gaps":["Erythrocyte binding conflicts with the 2012 study; the discrepancy is unresolved","Rhoptry bulb versus microneme localization diverges from earlier report","Direct erythrocyte receptor for TRAMP not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Structural determination defined TRAMP's molecular role as an anchoring partner, showing it forms a PfCSS–PfTRAMP complex that captures the PfRIPR tail to tether the PfRCR invasion complex to the merozoite surface.","evidence":"Cryo-EM structure of the PfRCR complex with erythrocyte-binding assay and structural modelling in P. falciparum","pmids":["38123677"],"confidence":"High","gaps":["Whether TRAMP contributes affinity or only scaffolding to receptor engagement not dissected","Stoichiometry and dynamics of the PfCSS–PfTRAMP complex during live invasion not defined","Relationship of this membrane-anchoring role to the earlier reported EBA175-triggered secretion not integrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unresolved whether TRAMP itself directly engages an erythrocyte receptor or acts purely as a surface-anchoring scaffold for the PfRCR complex, and the conflicting erythrocyte-binding data have not been reconciled.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined erythrocyte receptor for TRAMP","Binding-positive and binding-negative results not reconciled across studies","No genetic loss-of-function phenotype in the corpus to establish essentiality"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfCSS-PfTRAMP complex on the parasite membrane [#4]","Membrane-anchoring module linked to the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) via the PfRIPR tail [#4]"],"partners":["PFCSS [#4]","PFRIPR (ELONGATED TAIL) [#4]","PFSUB2 (SHEDDASE) [#1]"],"other_free_text":["Localization contested: developing micronemes/apical organelles co-localizing with AMA-1 [#0] versus rhoptry bulb [#3].","Erythrocyte-binding data conflict: recombinant extracellular domain did not bind erythrocytes [#2], while native and recombinant TRAMP bound untreated and protease/neuraminidase-treated erythrocytes [#3].","Rhoptry release of TRAMP is triggered by EBA175 adhesion to glycophorin A [#3].","Anti-TRAMP antibodies block invasion additively with anti-EBA175 antibodies [#3], but failed to inhibit growth in a separate assay [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15003842","id":"PMC_15003842","title":"PTRAMP; a conserved Plasmodium thrombospondin-related apical merozoite protein.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15003842","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23387921","id":"PMC_23387921","title":"A thrombospondin structural repeat containing rhoptry protein from Plasmodium falciparum mediates erythrocyte invasion.","date":"2013","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23387921","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16879884","id":"PMC_16879884","title":"Plasmodium thrombospondin related apical merozoite protein (PTRAMP) is shed from the surface of merozoites by PfSUB2 upon invasion of erythrocytes.","date":"2006","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/16879884","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38123677","id":"PMC_38123677","title":"The PfRCR complex bridges malaria parasite and erythrocyte during invasion.","date":"2023","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/38123677","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22467743","id":"PMC_22467743","title":"Analysis of the conformation and function of the Plasmodium falciparum merozoite proteins MTRAP and PTRAMP.","date":"2012","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/22467743","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36378331","id":"PMC_36378331","title":"Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia.","date":"2022","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/36378331","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TRAMP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36360181","id":"PMC_36360181","title":"Genetic Diversity and Population Genetic Structure Analysis of Plasmodium knowlesi Thrombospondin-Related Apical Merozoite Protein (TRAMP) in Clinical Samples.","date":"2022","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/36360181","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TRAMP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39548790","id":"PMC_39548790","title":"Potential use of anti-thrombospondin-related apical merozoite protein (TRAMP) polyclonal antibodies in sandwich enzyme-linked immunosorbent assay (ELISA) for detection of Plasmodium knowlesi.","date":"2024","source":"Tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/39548790","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TRAMP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6365,"output_tokens":1517,"usd":0.020925,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6431,"output_tokens":2943,"usd":0.052865,"stage2_stop_reason":"end_turn"},"total_usd":0.07379,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"TRAMP (PF3D7_1218000) localizes to the apical organelles (developing micronemes) of P. falciparum and P. berghei merozoites within intraerythrocytic schizonts, co-localizing with AMA-1, and subsequently relocates onto the merozoite surface prior to or during invasion.\",\n      \"method\": \"Immunofluorescence localization in intraerythrocytic schizonts of P. falciparum and P. berghei\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunofluorescence replicated in two Plasmodium species in the same study, but no functional consequence explicitly demonstrated\",\n      \"pmids\": [\"15003842\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"TRAMP (PF3D7_1218000) is shed from the merozoite surface by the serine protease PfSUB2 upon invasion of erythrocytes.\",\n      \"method\": \"Biochemical shedding assay with protease identification\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct identification of the shed protease (PfSUB2), single lab, single study\",\n      \"pmids\": [\"16879884\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recombinant TRAMP (PF3D7_1218000) extracellular domain does not bind human erythrocytes in an erythrocyte binding assay, and TRAMP-specific antibodies failed to inhibit P. falciparum growth in vitro.\",\n      \"method\": \"Erythrocyte binding assay with recombinant protein; in vitro growth inhibition assay with antibodies\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct binding and inhibition assays with recombinant protein, single lab; results are negative for erythrocyte binding and invasion inhibition\",\n      \"pmids\": [\"22467743\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TRAMP (PF3D7_1218000) localizes to the rhoptry bulb (not micronemes) and is secreted during erythrocyte invasion. Both native and recombinant TRAMP bind untreated as well as neuraminidase-, trypsin-, and chymotrypsin-treated human erythrocytes. Release of TRAMP from rhoptries is triggered by adhesion of microneme protein EBA175 to its erythrocyte receptor glycophorin A. Antibodies against TRAMP block erythrocyte invasion, and combination with anti-EBA175 antibodies produces additive inhibition.\",\n      \"method\": \"Immunofluorescence localization; native and recombinant protein erythrocyte binding assays; invasion inhibition assays with polyclonal antibodies\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (localization, binding assay, inhibition assay) in a single lab; note conflict with 2012 study on erythrocyte binding\",\n      \"pmids\": [\"23387921\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TRAMP (PF3D7_1218000) forms a complex with PfCSS on the parasite membrane, and together the PfCSS-PfTRAMP complex is bound by the elongated tail of PfRIPR, linking the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) to the merozoite surface. This positions the PfRCR structured core to present PfRH5 and PfCyRPA for interaction with erythrocyte receptors during invasion.\",\n      \"method\": \"Cryo-electron microscopy structure determination of the PfRCR complex; erythrocyte-binding assay; structural modelling\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure of the complex combined with binding assay and modelling, published in high-impact peer-reviewed journal with multiple orthogonal methods\",\n      \"pmids\": [\"38123677\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TRAMP (PF3D7_1218000) is a merozoite apical membrane protein that localizes to rhoptries/micronemes and is shed from the merozoite surface by PfSUB2 during erythrocyte invasion; it forms a complex with PfCSS on the parasite membrane, where it anchors the PfRIPR tail and thereby tethers the PfRCR invasion complex (containing PfRH5, PfCyRPA, and PfRIPR) to the merozoite surface to facilitate erythrocyte receptor engagement.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TRAMP (PF3D7_1218000) is a thrombospondin-related apical membrane protein of the Plasmodium merozoite that participates in erythrocyte invasion by tethering the invasion machinery to the parasite surface [#4]. It is an apical organelle protein of intraerythrocytic schizont-stage merozoites in both P. falciparum and P. berghei that relocates onto the merozoite surface prior to or during invasion [#0], and in P. falciparum it is shed from the surface by the serine protease PfSUB2 during erythrocyte entry [#1]. Its secretion from rhoptries is triggered by adhesion of the microneme protein EBA175 to its erythrocyte receptor glycophorin A, and antibodies against TRAMP block invasion, additively with anti-EBA175 antibodies [#3]. Structurally, TRAMP forms a complex with PfCSS on the parasite membrane; this PfCSS–PfTRAMP module is engaged by the elongated tail of PfRIPR, thereby linking the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) to the merozoite surface and positioning PfRH5 and PfCyRPA to engage erythrocyte receptors during invasion [#4]. Reports of TRAMP's direct erythrocyte-binding activity diverge across studies: recombinant TRAMP failed to bind erythrocytes in one assay [#2], whereas native and recombinant TRAMP bound treated and untreated erythrocytes in another [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing where TRAMP resides and when it becomes accessible was the first step in placing it in the invasion pathway; localization to developing apical organelles with subsequent surface relocation marked it as an invasion-stage protein.\",\n      \"evidence\": \"Immunofluorescence localization in intraerythrocytic schizonts of P. falciparum and P. berghei, co-localizing with AMA-1\",\n      \"pmids\": [\"15003842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional consequence of localization demonstrated\",\n        \"Whether apical residence is micronemal versus rhoptry was not resolved here (later contested)\",\n        \"Trigger and mechanism of surface relocation not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identifying the protease that removes TRAMP from the merozoite surface connected its dynamics to the regulated proteolytic events of invasion.\",\n      \"evidence\": \"Biochemical shedding assay with identification of PfSUB2 as the sheddase in P. falciparum\",\n      \"pmids\": [\"16879884\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study\",\n        \"Functional consequence of shedding for invasion not shown\",\n        \"Cleavage site and kinetics not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Testing whether TRAMP is a direct erythrocyte adhesin and a vaccine-relevant invasion target gave negative results, constraining early functional models.\",\n      \"evidence\": \"Erythrocyte binding assay with recombinant extracellular domain and in vitro growth inhibition assay with TRAMP antibodies\",\n      \"pmids\": [\"22467743\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative binding result conflicts with the 2013 study\",\n        \"Recombinant domain may not reproduce native conformation\",\n        \"Antibody epitopes and accessibility not characterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Re-examination placed TRAMP in the rhoptry bulb and linked its secretion to EBA175–glycophorin A engagement, arguing for a functional role in invasion supported by antibody inhibition.\",\n      \"evidence\": \"Immunofluorescence localization, native and recombinant erythrocyte binding assays, and invasion inhibition assays with polyclonal antibodies in P. falciparum\",\n      \"pmids\": [\"23387921\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Erythrocyte binding conflicts with the 2012 study; the discrepancy is unresolved\",\n        \"Rhoptry bulb versus microneme localization diverges from earlier report\",\n        \"Direct erythrocyte receptor for TRAMP not identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Structural determination defined TRAMP's molecular role as an anchoring partner, showing it forms a PfCSS–PfTRAMP complex that captures the PfRIPR tail to tether the PfRCR invasion complex to the merozoite surface.\",\n      \"evidence\": \"Cryo-EM structure of the PfRCR complex with erythrocyte-binding assay and structural modelling in P. falciparum\",\n      \"pmids\": [\"38123677\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TRAMP contributes affinity or only scaffolding to receptor engagement not dissected\",\n        \"Stoichiometry and dynamics of the PfCSS–PfTRAMP complex during live invasion not defined\",\n        \"Relationship of this membrane-anchoring role to the earlier reported EBA175-triggered secretion not integrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved whether TRAMP itself directly engages an erythrocyte receptor or acts purely as a surface-anchoring scaffold for the PfRCR complex, and the conflicting erythrocyte-binding data have not been reconciled.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined erythrocyte receptor for TRAMP\",\n        \"Binding-positive and binding-negative results not reconciled across studies\",\n        \"No genetic loss-of-function phenotype in the corpus to establish essentiality\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020008\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\n      \"PfCSS-PfTRAMP complex on the parasite membrane [#4]\",\n      \"Membrane-anchoring module linked to the PfRCR complex (PfRH5, PfCyRPA, PfRIPR) via the PfRIPR tail [#4]\"\n    ],\n    \"partners\": [\n      \"PfCSS [#4]\",\n      \"PfRIPR (elongated tail) [#4]\",\n      \"PfSUB2 (sheddase) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"Localization contested: developing micronemes/apical organelles co-localizing with AMA-1 [#0] versus rhoptry bulb [#3].\",\n      \"Erythrocyte-binding data conflict: recombinant extracellular domain did not bind erythrocytes [#2], while native and recombinant TRAMP bound untreated and protease/neuraminidase-treated erythrocytes [#3].\",\n      \"Rhoptry release of TRAMP is triggered by EBA175 adhesion to glycophorin A [#3].\",\n      \"Anti-TRAMP antibodies block invasion additively with anti-EBA175 antibodies [#3], but failed to inhibit growth in a separate assay [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1218000","name":null,"product":"thrombospondin-related apical membrane protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1433600","name":null,"product":"thrombospondin-related apical membrane protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1437600","name":null,"product":"thrombospondin-related apical membrane protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"TRAMP","evaluation":null}