{"gene":"PF3D7_1028700","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2005,"finding":"MTRAP (PF3D7_1028700) was identified as a merozoite-specific micronemal protein that shares key structural features with TRAP, including a thrombospondin repeat domain, a putative rhomboid-protease cleavage site, and a cytoplasmic tail that in vitro binds the actin-binding protein aldolase, suggesting it links extracellular adhesion to the actin-myosin motor in merozoites.","method":"In vitro aldolase binding assay; bioinformatic domain analysis; protein localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, in vitro binding assay with aldolase, supported by structural domain analysis; no genetic complementation or mutagenesis reported in this paper","pmids":["16321976"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"MTRAP (PF3D7_1028700) is a substrate of P. falciparum rhomboid proteases: PfROM4 efficiently cleaved MTRAP in a heterologous assay, with cleavage dependent on the MTRAP transmembrane domain.","method":"Heterologous rhomboid protease cleavage assay using recombinant PfROM4 and PfROM1","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzymatic assay with substrate specificity demonstrated; single lab but multiple substrates tested with clear specificity controls","pmids":["17040128"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Semaphorin-7A (CD108), a GPI-linked erythrocyte surface protein, was identified as a specific receptor for MTRAP (PF3D7_1028700). Two MTRAP monomers interact via their tandem TSR domains with the Sema domains of a Semaphorin-7A homodimer. The interaction was saturable, with quantified equilibrium and kinetic binding parameters determined by surface plasmon resonance. However, attempts to block this interaction during in vitro erythrocyte invasion assays using recombinant proteins and antibodies showed no significant inhibitory effect.","method":"AVEXIS extracellular protein interaction screen; surface plasmon resonance; recombinant protein binding assays; in vitro invasion inhibition assay (negative result for inhibition)","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — systematic screening followed by quantitative biophysical characterization (SPR) with domain-mapping; multiple orthogonal methods in one study","pmids":["23166499"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"MTRAP (PF3D7_1028700) is dispensable for erythrocyte invasion by merozoites, but is essential for gamete egress from erythrocytes. Specifically, MTRAP is required for disruption of the gamete-containing parasitophorous vacuole membrane, and MTRAP-deficient parasites fail to transmit to mosquitoes.","method":"Genetic knockout of MTRAP in P. berghei and P. falciparum; phenotypic analysis of erythrocyte invasion and gamete egress; parasitophorous vacuole membrane disruption assay","journal":"Cell host & microbe","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockouts in two Plasmodium species (P. berghei and P. falciparum) with specific cellular phenotype readouts; replicated across species","pmids":["27832590"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Recombinant MTRAP (PF3D7_1028700) adopts a highly extended conformation (approximately 2 nm × 33 nm) and binds human erythrocytes; this erythrocyte binding is mediated through the TSR domain. Antibodies against MTRAP did not inhibit P. falciparum development in vitro.","method":"Recombinant protein production in E. coli; dynamic light scattering/electron microscopy for structural analysis; erythrocyte binding assay; domain deletion analysis; in vitro growth inhibition assay (negative result)","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay with domain-level resolution and structural characterization; single lab; inhibition assay was negative","pmids":["22467743"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"The putative pantothenate transporter PAT in P. berghei is a membrane component of micronemes in sporozoites and is required for secretion of TRAP-containing vesicles; PAT-deficient sporozoites fail to secrete TRAP, are immotile, and cannot infect the rodent host. (This finding is about TRAP secretion machinery, not MTRAP directly, but demonstrates the micronemal secretion pathway relevant to the TRAP family.)","method":"Genetic disruption of PAT; immunofluorescence localization; sporozoite motility assay","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — this finding concerns the P. berghei TRAP (not MTRAP/PF3D7_1028700); only indirectly relevant to MTRAP's micronemal localization context","pmids":["27427910"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"finding":"O-fucosylation of TSR-domain-containing proteins by POFUT2 in P. falciparum ensures correct protein trafficking and stability; disruption of POFUT2 leads to destabilization and incorrect trafficking of TSR-bearing proteins. MTRAP (PF3D7_1028700), as a TSR-domain protein, is implicated in this glycosylation-dependent ER quality control mechanism, though specific MTRAP phenotypes are not individually resolved in the abstract.","method":"Genetic disruption of POFUT2; proteomics; phenotypic analysis of life cycle stages","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — MTRAP is listed among TSR proteins affected but is not individually characterized in the abstract; indirect inference","pmids":["28916755"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Glycosylation of MTRAP's (PF3D7_1028700 is a merozoite protein; this finding concerns PfTRAP, a distinct sporozoite protein — excluded from MTRAP findings).","method":"N/A","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Excluded — this paper concerns PfTRAP (sporozoite protein), not MTRAP/PF3D7_1028700","pmids":["40667256"],"is_preprint":true,"attribution":[]}],"current_model":"MTRAP (PF3D7_1028700) is a merozoite-specific micronemal protein belonging to the TRAP family that localizes to micronemes, contains a TSR domain and a cytoplasmic tail that binds aldolase in vitro linking it to the actin-myosin motor, is cleaved by PfROM4 rhomboid protease via its transmembrane domain, binds erythrocytes through its TSR domain with Semaphorin-7A (CD108) as the erythrocyte receptor, is dispensable for merozoite invasion of erythrocytes, but is essential for gamete egress by mediating disruption of the parasitophorous vacuole membrane, thereby being required for parasite transmission to mosquitoes."},"narrative":{"mechanistic_narrative":"MTRAP (PF3D7_1028700) is a merozoite-specific micronemal protein of the TRAP family that couples extracellular adhesion to the intracellular actin-myosin motor and, unexpectedly, is essential not for invasion but for sexual-stage egress and parasite transmission [PMID:16321976, PMID:27832590]. Its architecture is that of a canonical TRAP-family adhesin: an extended (~2 nm × 33 nm) ectodomain built around thrombospondin repeat (TSR) domains, a rhomboid-cleavable transmembrane segment, and a cytoplasmic tail that binds the glycolytic/actin-binding protein aldolase in vitro, providing the molecular bridge to the motor [PMID:16321976, PMID:22467743]. The TSR domains mediate erythrocyte binding, and Semaphorin-7A (CD108) was identified as an erythrocyte-surface receptor engaged by the tandem TSR domains, with two MTRAP monomers binding a Semaphorin-7A homodimer [PMID:23166499, PMID:22467743]. MTRAP is processed by the rhomboid protease PfROM4, and cleavage depends on its transmembrane domain, consistent with regulated shedding during motility/egress [PMID:17040128]. Genetic knockout in P. berghei and P. falciparum shows MTRAP is dispensable for merozoite invasion of erythrocytes but is required for disruption of the parasitophorous vacuole membrane during gamete egress, and MTRAP-deficient parasites fail to transmit to mosquitoes [PMID:27832590]; consistent with this, anti-MTRAP antibodies and recombinant-protein blockade do not inhibit erythrocyte invasion in vitro [PMID:23166499, PMID:22467743]. How the TSR/Semaphorin-7A interaction relates mechanistically to the vacuole-membrane-disruption role in gametes has not been resolved in the available corpus.","teleology":[{"year":2005,"claim":"Establishing that MTRAP is a TRAP-family micronemal adhesin defined its candidate role as a link between surface adhesion and the actin-myosin invasion motor in merozoites.","evidence":"In vitro aldolase-binding assay, bioinformatic domain analysis, and localization in P. falciparum","pmids":["16321976"],"confidence":"Medium","gaps":["Aldolase binding shown only in vitro, not validated by mutagenesis or in the parasite","Functional consequence of the motor linkage was not tested","No genetic loss-of-function to confirm a role in invasion"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Identifying MTRAP as a rhomboid substrate showed how the adhesin could be regulated by proteolytic shedding at its transmembrane anchor.","evidence":"Heterologous rhomboid cleavage assay with recombinant PfROM4/PfROM1 showing TMD-dependent cleavage","pmids":["17040128"],"confidence":"Medium","gaps":["Cleavage demonstrated in a heterologous system, not in the parasite","Timing and biological trigger of cleavage during the life cycle not established","No link between cleavage and the egress phenotype"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Structural characterization and receptor identification defined MTRAP as an extended TSR-bearing molecule that binds erythrocytes, with Semaphorin-7A as its receptor.","evidence":"Recombinant protein production, EM/DLS structural analysis, erythrocyte-binding and domain-deletion assays, AVEXIS screen, and SPR in P. falciparum","pmids":["22467743","23166499"],"confidence":"High","gaps":["Recombinant blockade and anti-MTRAP antibodies did not inhibit invasion, leaving the functional purpose of erythrocyte binding unclear","Relevance of the Semaphorin-7A interaction to any life-cycle stage not established","Stoichiometry-to-function relationship untested in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Genetic knockout overturned the expected invasion role and revealed MTRAP's essential function in gamete egress and transmission.","evidence":"MTRAP knockouts in P. berghei and P. falciparum with invasion, gamete-egress, PVM-disruption, and mosquito-transmission readouts","pmids":["27832590"],"confidence":"High","gaps":["Molecular mechanism by which MTRAP drives PVM disruption is unknown","Whether the TSR/Semaphorin-7A or aldolase interactions participate in egress is unresolved","Role, if any, of PfROM4 cleavage in the egress function not addressed"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"TSR O-fucosylation by POFUT2 was implicated in ER quality control of TSR proteins, providing a possible trafficking/stability determinant for MTRAP.","evidence":"POFUT2 disruption with proteomics and life-cycle phenotyping in P. falciparum; MTRAP inferred as one affected TSR protein","pmids":["28916755"],"confidence":"Low","gaps":["MTRAP-specific effect not individually resolved; inference from TSR-protein class","No direct demonstration of MTRAP fucosylation or trafficking defect","Link to the egress phenotype untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How MTRAP mechanistically mediates parasitophorous vacuole membrane disruption during gamete egress, and whether its TSR/Semaphorin-7A binding, aldolase linkage, or PfROM4 cleavage contribute to that role, remains open.","evidence":"No direct experimental evidence in the available corpus connecting the biochemical interactions to the egress mechanism","pmids":[],"confidence":"Low","gaps":["No molecular model linking MTRAP interactions to PVM disruption","No structure of MTRAP in its egress-relevant context","Functional partners of MTRAP at egress unidentified"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ALDOLASE (IN VITRO, VIA CYTOPLASMIC TAIL) [#0]","PFROM4 RHOMBOID PROTEASE (SUBSTRATE) [#1]","SEMAPHORIN-7A / CD108 (ERYTHROCYTE RECEPTOR) [#2]"],"other_free_text":["Contains tandem thrombospondin repeat (TSR) domains that mediate erythrocyte binding [#4]","Adopts an extended ~2 nm x 33 nm conformation [#4]","Cleavage by PfROM4 depends on the transmembrane domain [#1]","Dispensable for merozoite invasion but essential for gamete egress via PVM disruption; required for mosquito transmission [#3]","Anti-MTRAP antibodies and recombinant-protein blockade do not inhibit invasion/development in vitro [#2, #4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"9267031","id":"PMC_9267031","title":"TRAP is necessary for gliding motility and infectivity of plasmodium 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site, and a cytoplasmic tail that in vitro binds the actin-binding protein aldolase, suggesting it links extracellular adhesion to the actin-myosin motor in merozoites.\",\n      \"method\": \"In vitro aldolase binding assay; bioinformatic domain analysis; protein localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, in vitro binding assay with aldolase, supported by structural domain analysis; no genetic complementation or mutagenesis reported in this paper\",\n      \"pmids\": [\"16321976\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MTRAP (PF3D7_1028700) is a substrate of P. falciparum rhomboid proteases: PfROM4 efficiently cleaved MTRAP in a heterologous assay, with cleavage dependent on the MTRAP transmembrane domain.\",\n      \"method\": \"Heterologous rhomboid protease cleavage assay using recombinant PfROM4 and PfROM1\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzymatic assay with substrate specificity demonstrated; single lab but multiple substrates tested with clear specificity controls\",\n      \"pmids\": [\"17040128\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Semaphorin-7A (CD108), a GPI-linked erythrocyte surface protein, was identified as a specific receptor for MTRAP (PF3D7_1028700). Two MTRAP monomers interact via their tandem TSR domains with the Sema domains of a Semaphorin-7A homodimer. The interaction was saturable, with quantified equilibrium and kinetic binding parameters determined by surface plasmon resonance. However, attempts to block this interaction during in vitro erythrocyte invasion assays using recombinant proteins and antibodies showed no significant inhibitory effect.\",\n      \"method\": \"AVEXIS extracellular protein interaction screen; surface plasmon resonance; recombinant protein binding assays; in vitro invasion inhibition assay (negative result for inhibition)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — systematic screening followed by quantitative biophysical characterization (SPR) with domain-mapping; multiple orthogonal methods in one study\",\n      \"pmids\": [\"23166499\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MTRAP (PF3D7_1028700) is dispensable for erythrocyte invasion by merozoites, but is essential for gamete egress from erythrocytes. Specifically, MTRAP is required for disruption of the gamete-containing parasitophorous vacuole membrane, and MTRAP-deficient parasites fail to transmit to mosquitoes.\",\n      \"method\": \"Genetic knockout of MTRAP in P. berghei and P. falciparum; phenotypic analysis of erythrocyte invasion and gamete egress; parasitophorous vacuole membrane disruption assay\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockouts in two Plasmodium species (P. berghei and P. falciparum) with specific cellular phenotype readouts; replicated across species\",\n      \"pmids\": [\"27832590\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recombinant MTRAP (PF3D7_1028700) adopts a highly extended conformation (approximately 2 nm × 33 nm) and binds human erythrocytes; this erythrocyte binding is mediated through the TSR domain. Antibodies against MTRAP did not inhibit P. falciparum development in vitro.\",\n      \"method\": \"Recombinant protein production in E. coli; dynamic light scattering/electron microscopy for structural analysis; erythrocyte binding assay; domain deletion analysis; in vitro growth inhibition assay (negative result)\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay with domain-level resolution and structural characterization; single lab; inhibition assay was negative\",\n      \"pmids\": [\"22467743\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The putative pantothenate transporter PAT in P. berghei is a membrane component of micronemes in sporozoites and is required for secretion of TRAP-containing vesicles; PAT-deficient sporozoites fail to secrete TRAP, are immotile, and cannot infect the rodent host. (This finding is about TRAP secretion machinery, not MTRAP directly, but demonstrates the micronemal secretion pathway relevant to the TRAP family.)\",\n      \"method\": \"Genetic disruption of PAT; immunofluorescence localization; sporozoite motility assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — this finding concerns the P. berghei TRAP (not MTRAP/PF3D7_1028700); only indirectly relevant to MTRAP's micronemal localization context\",\n      \"pmids\": [\"27427910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"O-fucosylation of TSR-domain-containing proteins by POFUT2 in P. falciparum ensures correct protein trafficking and stability; disruption of POFUT2 leads to destabilization and incorrect trafficking of TSR-bearing proteins. MTRAP (PF3D7_1028700), as a TSR-domain protein, is implicated in this glycosylation-dependent ER quality control mechanism, though specific MTRAP phenotypes are not individually resolved in the abstract.\",\n      \"method\": \"Genetic disruption of POFUT2; proteomics; phenotypic analysis of life cycle stages\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — MTRAP is listed among TSR proteins affected but is not individually characterized in the abstract; indirect inference\",\n      \"pmids\": [\"28916755\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Glycosylation of MTRAP's (PF3D7_1028700 is a merozoite protein; this finding concerns PfTRAP, a distinct sporozoite protein — excluded from MTRAP findings).\",\n      \"method\": \"N/A\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Excluded — this paper concerns PfTRAP (sporozoite protein), not MTRAP/PF3D7_1028700\",\n      \"pmids\": [\"40667256\"],\n      \"is_preprint\": true,\n      \"attribution\": []\n    }\n  ],\n  \"current_model\": \"MTRAP (PF3D7_1028700) is a merozoite-specific micronemal protein belonging to the TRAP family that localizes to micronemes, contains a TSR domain and a cytoplasmic tail that binds aldolase in vitro linking it to the actin-myosin motor, is cleaved by PfROM4 rhomboid protease via its transmembrane domain, binds erythrocytes through its TSR domain with Semaphorin-7A (CD108) as the erythrocyte receptor, is dispensable for merozoite invasion of erythrocytes, but is essential for gamete egress by mediating disruption of the parasitophorous vacuole membrane, thereby being required for parasite transmission to mosquitoes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MTRAP (PF3D7_1028700) is a merozoite-specific micronemal protein of the TRAP family that couples extracellular adhesion to the intracellular actin-myosin motor and, unexpectedly, is essential not for invasion but for sexual-stage egress and parasite transmission [#0, #3]. Its architecture is that of a canonical TRAP-family adhesin: an extended (~2 nm × 33 nm) ectodomain built around thrombospondin repeat (TSR) domains, a rhomboid-cleavable transmembrane segment, and a cytoplasmic tail that binds the glycolytic/actin-binding protein aldolase in vitro, providing the molecular bridge to the motor [#0, #4]. The TSR domains mediate erythrocyte binding, and Semaphorin-7A (CD108) was identified as an erythrocyte-surface receptor engaged by the tandem TSR domains, with two MTRAP monomers binding a Semaphorin-7A homodimer [#2, #4]. MTRAP is processed by the rhomboid protease PfROM4, and cleavage depends on its transmembrane domain, consistent with regulated shedding during motility/egress [#1]. Genetic knockout in P. berghei and P. falciparum shows MTRAP is dispensable for merozoite invasion of erythrocytes but is required for disruption of the parasitophorous vacuole membrane during gamete egress, and MTRAP-deficient parasites fail to transmit to mosquitoes [#3]; consistent with this, anti-MTRAP antibodies and recombinant-protein blockade do not inhibit erythrocyte invasion in vitro [#2, #4]. How the TSR/Semaphorin-7A interaction relates mechanistically to the vacuole-membrane-disruption role in gametes has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing that MTRAP is a TRAP-family micronemal adhesin defined its candidate role as a link between surface adhesion and the actin-myosin invasion motor in merozoites.\",\n      \"evidence\": \"In vitro aldolase-binding assay, bioinformatic domain analysis, and localization in P. falciparum\",\n      \"pmids\": [\"16321976\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Aldolase binding shown only in vitro, not validated by mutagenesis or in the parasite\",\n        \"Functional consequence of the motor linkage was not tested\",\n        \"No genetic loss-of-function to confirm a role in invasion\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identifying MTRAP as a rhomboid substrate showed how the adhesin could be regulated by proteolytic shedding at its transmembrane anchor.\",\n      \"evidence\": \"Heterologous rhomboid cleavage assay with recombinant PfROM4/PfROM1 showing TMD-dependent cleavage\",\n      \"pmids\": [\"17040128\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cleavage demonstrated in a heterologous system, not in the parasite\",\n        \"Timing and biological trigger of cleavage during the life cycle not established\",\n        \"No link between cleavage and the egress phenotype\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Structural characterization and receptor identification defined MTRAP as an extended TSR-bearing molecule that binds erythrocytes, with Semaphorin-7A as its receptor.\",\n      \"evidence\": \"Recombinant protein production, EM/DLS structural analysis, erythrocyte-binding and domain-deletion assays, AVEXIS screen, and SPR in P. falciparum\",\n      \"pmids\": [\"22467743\", \"23166499\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Recombinant blockade and anti-MTRAP antibodies did not inhibit invasion, leaving the functional purpose of erythrocyte binding unclear\",\n        \"Relevance of the Semaphorin-7A interaction to any life-cycle stage not established\",\n        \"Stoichiometry-to-function relationship untested in vivo\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Genetic knockout overturned the expected invasion role and revealed MTRAP's essential function in gamete egress and transmission.\",\n      \"evidence\": \"MTRAP knockouts in P. berghei and P. falciparum with invasion, gamete-egress, PVM-disruption, and mosquito-transmission readouts\",\n      \"pmids\": [\"27832590\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which MTRAP drives PVM disruption is unknown\",\n        \"Whether the TSR/Semaphorin-7A or aldolase interactions participate in egress is unresolved\",\n        \"Role, if any, of PfROM4 cleavage in the egress function not addressed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"TSR O-fucosylation by POFUT2 was implicated in ER quality control of TSR proteins, providing a possible trafficking/stability determinant for MTRAP.\",\n      \"evidence\": \"POFUT2 disruption with proteomics and life-cycle phenotyping in P. falciparum; MTRAP inferred as one affected TSR protein\",\n      \"pmids\": [\"28916755\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"MTRAP-specific effect not individually resolved; inference from TSR-protein class\",\n        \"No direct demonstration of MTRAP fucosylation or trafficking defect\",\n        \"Link to the egress phenotype untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MTRAP mechanistically mediates parasitophorous vacuole membrane disruption during gamete egress, and whether its TSR/Semaphorin-7A binding, aldolase linkage, or PfROM4 cleavage contribute to that role, remains open.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus connecting the biochemical interactions to the egress mechanism\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No molecular model linking MTRAP interactions to PVM disruption\",\n        \"No structure of MTRAP in its egress-relevant context\",\n        \"Functional partners of MTRAP at egress unidentified\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0050839\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0051015\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0030728\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Aldolase (in vitro, via cytoplasmic tail) [#0]\",\n      \"PfROM4 rhomboid protease (substrate) [#1]\",\n      \"Semaphorin-7A / CD108 (erythrocyte receptor) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"Contains tandem thrombospondin repeat (TSR) domains that mediate erythrocyte binding [#4]\",\n      \"Adopts an extended ~2 nm x 33 nm conformation [#4]\",\n      \"Cleavage by PfROM4 depends on the transmembrane domain [#1]\",\n      \"Dispensable for merozoite invasion but essential for gamete egress via PVM disruption; required for mosquito transmission [#3]\",\n      \"Anti-MTRAP antibodies and recombinant-protein blockade do not inhibit invasion/development in vitro [#2, #4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1028700","name":null,"product":"merozoite TRAP-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0512800","name":null,"product":"merozoite TRAP-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0613400","name":null,"product":"merozoite TRAP-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MTRAP","evaluation":null}