{"gene":"PF3D7_0517800","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2009,"finding":"DCX (apicortin) was identified in silico as a protein containing two microtubule-binding domains: a DCX (doublecortin) domain and a partial p25-alpha domain, both associated with microtubule binding and stabilizing properties, suggesting a role as a microtubule-associated protein in Apicomplexan cytoskeletal structures such as subpellicular microtubules and apical polar rings.","method":"Bioinformatic/in silico domain analysis; supported by proteomics data from an independent study","journal":"Infection, genetics and evolution","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct biochemical validation in this paper","pmids":["19778640"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"DCX (apicortin) expression was downregulated at both RNA and protein levels by erythrocytic miR-150-3p and miR-197-5p in a cell-line model. Loading synthetic mimics of these miRNAs into erythrocytes prior to parasite invasion reduced parasite growth, impaired invasion, reduced micronemal secretion, and reduced AMA1 secretion, establishing a functional link between DCX expression and microneme-dependent invasion.","method":"Co-expression of apicortin and miRNA mimics in cell line; miRNA loading into erythrocytes followed by invasion assays; Western blot for AMA1 secretion","journal":"Disease models & mechanisms","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, multiple orthogonal functional readouts (growth, invasion, micronemal secretion, AMA1 secretion) but no direct molecular interaction experiment; causal link to DCX is indirect (via miRNA-mediated knockdown)","pmids":["32493727"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"DCX (apicortin) interacts with P. falciparum α-tubulin-I and β-tubulin, as demonstrated by in vitro and in silico binding studies. Disruption of this interaction using Tamoxifen (a p25 domain-binding drug) inhibited parasite growth and blood-stage life-cycle progression.","method":"In silico docking and in vitro binding assays; pharmacological disruption with Tamoxifen followed by growth/life-cycle assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — in vitro binding plus functional pharmacological disruption in single lab; no mutagenesis or reconstitution to confirm binding interface","pmids":["33633135"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"In P. berghei, DCX (apicortin) localizes to a distinct ring-like structure at the apical end of invasive parasite stages (within the apical complex region), as shown by live-cell imaging of GFP-tagged apicortin and super-resolution/expansion microscopy. Genetic deletion of DCX had no effect on parasite development across the life cycle, indicating the protein is dispensable and that redundancy or compensatory mechanisms exist.","method":"Live-cell fluorescence imaging of GFP-tagged transgenic parasite line; super-resolution and expansion microscopy; gene deletion (knockout) with full life-cycle phenotyping","journal":"Life science alliance","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization by live imaging and super-resolution microscopy combined with clean genetic knockout and full life-cycle phenotyping in a single rigorous study","pmids":["41545195"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"DCX (PF3D7_0517800, apicortin) is a microtubule-associated protein containing a doublecortin (DCX) domain and a partial p25-alpha domain; in P. berghei it localizes as a ring-like structure at the apical complex of invasive stages, interacts with α- and β-tubulin in P. falciparum in vitro, and its knockdown in P. falciparum impairs parasite growth, invasion, and microneme secretion—yet complete genetic deletion in P. berghei causes no life-cycle defect, indicating functional redundancy at the apical complex."},"narrative":{"mechanistic_narrative":"DCX (PF3D7_0517800, apicortin) is a microtubule-associated protein of the apicomplexan cytoskeleton, defined by a doublecortin (DCX) domain and a partial p25-alpha domain both linked to microtubule binding and stabilization [PMID:19778640]. Consistent with this predicted role, DCX binds P. falciparum α-tubulin-I and β-tubulin in vitro, and pharmacological disruption of this interaction with the p25-domain-binding drug Tamoxifen inhibits parasite growth and blood-stage progression [PMID:33633135]. In P. berghei, DCX concentrates as a discrete ring-like structure at the apical end of invasive stages within the apical complex region [PMID:41545195]. Functionally, reducing DCX levels in P. falciparum—via erythrocytic miR-150-3p/miR-197-5p-mediated knockdown—impairs parasite growth, invasion, and microneme (including AMA1) secretion, tying DCX to microneme-dependent host-cell invasion [PMID:32493727]. However, clean genetic deletion of DCX in P. berghei produces no life-cycle defect, indicating the protein is dispensable and that redundant or compensatory mechanisms operate at the apical complex [PMID:41545195]. Beyond tubulin binding, its precise molecular contribution at the apical complex has not been resolved in the available corpus.","teleology":[{"year":2009,"claim":"Establishing whether PF3D7_0517800 could contribute to apicomplexan cytoskeleton, the finding predicted it as a microtubule-associated protein carrying two microtubule-binding domains.","evidence":"in silico domain analysis supported by independent proteomics","pmids":["19778640"],"confidence":"Low","gaps":["Computational prediction only, no direct biochemical validation in this paper","No demonstration of actual microtubule binding","No localization data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To test whether DCX levels matter for parasite biology, miRNA-mediated knockdown showed that reduced DCX expression impairs growth, invasion, and micronemal/AMA1 secretion, linking DCX to microneme-dependent invasion.","evidence":"miRNA mimic loading into erythrocytes with invasion assays and Western blot for AMA1 secretion in P. falciparum cell-line model","pmids":["32493727"],"confidence":"Medium","gaps":["Causal link is indirect through miRNA-mediated knockdown rather than direct DCX perturbation","No direct molecular interaction experiment","miRNAs may have off-target effects on other transcripts"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To move from predicted to demonstrated microtubule binding, binding assays showed DCX interacts with α-tubulin-I and β-tubulin, and disrupting this with Tamoxifen inhibited growth and blood-stage progression.","evidence":"in silico docking plus in vitro binding assays and pharmacological disruption with Tamoxifen in P. falciparum","pmids":["33633135"],"confidence":"Medium","gaps":["No mutagenesis or reconstitution to confirm the binding interface","Tamoxifen may act on targets beyond DCX","Interaction shown in vitro, not confirmed in parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"To localize DCX and test its necessity, imaging placed it as a ring-like apical-complex structure, while clean genetic knockout showed it is dispensable across the P. berghei life cycle, revealing redundancy.","evidence":"live-cell imaging of GFP-tagged parasites, super-resolution/expansion microscopy, and gene deletion with full life-cycle phenotyping in P. berghei","pmids":["41545195"],"confidence":"High","gaps":["Compensatory or redundant factors not identified","Apparent contradiction with P. falciparum knockdown phenotype unresolved (species difference vs. off-target)","Molecular function at the apical ring not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The precise molecular role of DCX at the apical complex, and the identity of factors that render it dispensable in P. berghei despite an invasion-linked knockdown phenotype in P. falciparum, remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mechanistic account reconciling the P. falciparum knockdown phenotype with the P. berghei knockout being phenotypically silent","Redundant partners at the apical complex not identified","No structural model of the DCX/p25-tubulin interaction"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["P. FALCIPARUM Α-TUBULIN-I [#2]","P. FALCIPARUM Β-TUBULIN [#2]"],"other_free_text":["Contains a doublecortin (DCX) domain and a partial p25-alpha domain, both associated with microtubule binding [#0].","DCX expression is downregulated by erythrocytic miR-150-3p and miR-197-5p, and lowering it impairs invasion and microneme/AMA1 secretion in P. falciparum [#1].","Tamoxifen, a p25-domain-binding drug, disrupts the DCX-tubulin interaction and inhibits P. falciparum growth and blood-stage progression [#2].","Localizes as a discrete ring-like structure at the apical complex of invasive P. berghei stages [#3].","Genetic deletion in P. berghei causes no life-cycle defect, indicating dispensability and functional redundancy [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32493727","id":"PMC_32493727","title":"Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion.","date":"2020","source":"Disease models & mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/32493727","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["apicortin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19778640","id":"PMC_19778640","title":"Apicortin, a unique protein, with a putative cytoskeletal role, shared only by apicomplexan parasites and the placozoan Trichoplax adhaerens.","date":"2009","source":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/19778640","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":"33633135","id":"PMC_33633135","title":"Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33633135","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["apicortin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27282556","id":"PMC_27282556","title":"Wider than Thought Phylogenetic Occurrence of Apicortin, A Characteristic Protein of Apicomplexan Parasites.","date":"2016","source":"Journal of molecular evolution","url":"https://pubmed.ncbi.nlm.nih.gov/27282556","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DCX","apicortin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34209186","id":"PMC_34209186","title":"Apicortin, a Constituent of Apicomplexan Conoid/Apical Complex and Its Tentative Role in Pathogen-Host Interaction.","date":"2021","source":"Tropical medicine and infectious disease","url":"https://pubmed.ncbi.nlm.nih.gov/34209186","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DCX","apicortin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41545195","id":"PMC_41545195","title":"Apicortin defines the Plasmodium apical conoid body but is dispensable for the parasite life cycle.","date":"2026","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/41545195","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["apicortin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5553,"output_tokens":1285,"usd":0.017967,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6183,"output_tokens":2478,"usd":0.046433,"stage2_stop_reason":"end_turn"},"total_usd":0.0644,"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\": 2009,\n      \"finding\": \"DCX (apicortin) was identified in silico as a protein containing two microtubule-binding domains: a DCX (doublecortin) domain and a partial p25-alpha domain, both associated with microtubule binding and stabilizing properties, suggesting a role as a microtubule-associated protein in Apicomplexan cytoskeletal structures such as subpellicular microtubules and apical polar rings.\",\n      \"method\": \"Bioinformatic/in silico domain analysis; supported by proteomics data from an independent study\",\n      \"journal\": \"Infection, genetics and evolution\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct biochemical validation in this paper\",\n      \"pmids\": [\"19778640\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DCX (apicortin) expression was downregulated at both RNA and protein levels by erythrocytic miR-150-3p and miR-197-5p in a cell-line model. Loading synthetic mimics of these miRNAs into erythrocytes prior to parasite invasion reduced parasite growth, impaired invasion, reduced micronemal secretion, and reduced AMA1 secretion, establishing a functional link between DCX expression and microneme-dependent invasion.\",\n      \"method\": \"Co-expression of apicortin and miRNA mimics in cell line; miRNA loading into erythrocytes followed by invasion assays; Western blot for AMA1 secretion\",\n      \"journal\": \"Disease models & mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, multiple orthogonal functional readouts (growth, invasion, micronemal secretion, AMA1 secretion) but no direct molecular interaction experiment; causal link to DCX is indirect (via miRNA-mediated knockdown)\",\n      \"pmids\": [\"32493727\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DCX (apicortin) interacts with P. falciparum α-tubulin-I and β-tubulin, as demonstrated by in vitro and in silico binding studies. Disruption of this interaction using Tamoxifen (a p25 domain-binding drug) inhibited parasite growth and blood-stage life-cycle progression.\",\n      \"method\": \"In silico docking and in vitro binding assays; pharmacological disruption with Tamoxifen followed by growth/life-cycle assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — in vitro binding plus functional pharmacological disruption in single lab; no mutagenesis or reconstitution to confirm binding interface\",\n      \"pmids\": [\"33633135\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In P. berghei, DCX (apicortin) localizes to a distinct ring-like structure at the apical end of invasive parasite stages (within the apical complex region), as shown by live-cell imaging of GFP-tagged apicortin and super-resolution/expansion microscopy. Genetic deletion of DCX had no effect on parasite development across the life cycle, indicating the protein is dispensable and that redundancy or compensatory mechanisms exist.\",\n      \"method\": \"Live-cell fluorescence imaging of GFP-tagged transgenic parasite line; super-resolution and expansion microscopy; gene deletion (knockout) with full life-cycle phenotyping\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization by live imaging and super-resolution microscopy combined with clean genetic knockout and full life-cycle phenotyping in a single rigorous study\",\n      \"pmids\": [\"41545195\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"DCX (PF3D7_0517800, apicortin) is a microtubule-associated protein containing a doublecortin (DCX) domain and a partial p25-alpha domain; in P. berghei it localizes as a ring-like structure at the apical complex of invasive stages, interacts with α- and β-tubulin in P. falciparum in vitro, and its knockdown in P. falciparum impairs parasite growth, invasion, and microneme secretion—yet complete genetic deletion in P. berghei causes no life-cycle defect, indicating functional redundancy at the apical complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DCX (PF3D7_0517800, apicortin) is a microtubule-associated protein of the apicomplexan cytoskeleton, defined by a doublecortin (DCX) domain and a partial p25-alpha domain both linked to microtubule binding and stabilization [#0]. Consistent with this predicted role, DCX binds P. falciparum \\u03b1-tubulin-I and \\u03b2-tubulin in vitro, and pharmacological disruption of this interaction with the p25-domain-binding drug Tamoxifen inhibits parasite growth and blood-stage progression [#2]. In P. berghei, DCX concentrates as a discrete ring-like structure at the apical end of invasive stages within the apical complex region [#3]. Functionally, reducing DCX levels in P. falciparum\\u2014via erythrocytic miR-150-3p/miR-197-5p-mediated knockdown\\u2014impairs parasite growth, invasion, and microneme (including AMA1) secretion, tying DCX to microneme-dependent host-cell invasion [#1]. However, clean genetic deletion of DCX in P. berghei produces no life-cycle defect, indicating the protein is dispensable and that redundant or compensatory mechanisms operate at the apical complex [#3]. Beyond tubulin binding, its precise molecular contribution at the apical complex has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing whether PF3D7_0517800 could contribute to apicomplexan cytoskeleton, the finding predicted it as a microtubule-associated protein carrying two microtubule-binding domains.\",\n      \"evidence\": \"in silico domain analysis supported by independent proteomics\",\n      \"pmids\": [\"19778640\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, no direct biochemical validation in this paper\",\n        \"No demonstration of actual microtubule binding\",\n        \"No localization data\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To test whether DCX levels matter for parasite biology, miRNA-mediated knockdown showed that reduced DCX expression impairs growth, invasion, and micronemal/AMA1 secretion, linking DCX to microneme-dependent invasion.\",\n      \"evidence\": \"miRNA mimic loading into erythrocytes with invasion assays and Western blot for AMA1 secretion in P. falciparum cell-line model\",\n      \"pmids\": [\"32493727\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Causal link is indirect through miRNA-mediated knockdown rather than direct DCX perturbation\",\n        \"No direct molecular interaction experiment\",\n        \"miRNAs may have off-target effects on other transcripts\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To move from predicted to demonstrated microtubule binding, binding assays showed DCX interacts with \\u03b1-tubulin-I and \\u03b2-tubulin, and disrupting this with Tamoxifen inhibited growth and blood-stage progression.\",\n      \"evidence\": \"in silico docking plus in vitro binding assays and pharmacological disruption with Tamoxifen in P. falciparum\",\n      \"pmids\": [\"33633135\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis or reconstitution to confirm the binding interface\",\n        \"Tamoxifen may act on targets beyond DCX\",\n        \"Interaction shown in vitro, not confirmed in parasites\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"To localize DCX and test its necessity, imaging placed it as a ring-like apical-complex structure, while clean genetic knockout showed it is dispensable across the P. berghei life cycle, revealing redundancy.\",\n      \"evidence\": \"live-cell imaging of GFP-tagged parasites, super-resolution/expansion microscopy, and gene deletion with full life-cycle phenotyping in P. berghei\",\n      \"pmids\": [\"41545195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Compensatory or redundant factors not identified\",\n        \"Apparent contradiction with P. falciparum knockdown phenotype unresolved (species difference vs. off-target)\",\n        \"Molecular function at the apical ring not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular role of DCX at the apical complex, and the identity of factors that render it dispensable in P. berghei despite an invasion-linked knockdown phenotype in P. falciparum, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mechanistic account reconciling the P. falciparum knockdown phenotype with the P. berghei knockout being phenotypically silent\",\n        \"Redundant partners at the apical complex not identified\",\n        \"No structural model of the DCX/p25-tubulin interaction\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0048487\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020007\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0070588\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0002377\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"P. falciparum \\u03b1-tubulin-I [#2]\",\n      \"P. falciparum \\u03b2-tubulin [#2]\"\n    ],\n    \"other_free_text\": [\n      \"Contains a doublecortin (DCX) domain and a partial p25-alpha domain, both associated with microtubule binding [#0].\",\n      \"DCX expression is downregulated by erythrocytic miR-150-3p and miR-197-5p, and lowering it impairs invasion and microneme/AMA1 secretion in P. falciparum [#1].\",\n      \"Tamoxifen, a p25-domain-binding drug, disrupts the DCX-tubulin interaction and inhibits P. falciparum growth and blood-stage progression [#2].\",\n      \"Localizes as a discrete ring-like structure at the apical complex of invasive P. berghei stages [#3].\",\n      \"Genetic deletion in P. berghei causes no life-cycle defect, indicating dispensability and functional redundancy [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0517800","name":null,"product":"apicortin","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1232600","name":null,"product":"doublecortin domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1015500","name":null,"product":"doublecortin domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DCX","evaluation":null}