{"gene":"PF3D7_0718000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2024,"finding":"In P. yoelii ookinetes, DHC3 (a putative dynein heavy chain) localizes to subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection, and defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, functioning as receptors for cargoes driven by the SPMT-dynein motor.","method":"Genetic disruption (KO), live imaging/localization, co-immunoprecipitation (Rab11A/Rab11B interaction with DHC3), phenotypic analysis of ookinete morphogenesis and mosquito infection","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction (Co-IP with Rab11A/B), KO with defined cellular phenotype, direct localization; single lab, but multiple orthogonal methods. Note: this paper studies DHC3 in P. yoelii; PF3D7_0718000 is the P. falciparum putative dynein heavy chain and may or may not be the direct ortholog of DHC3.","pmids":["39366980"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2015,"finding":"In P. falciparum, the dynein heavy chain-like protein forms 4-HNE (4-hydroxynonenal) conjugates in response to oxidative stress induced by the endoperoxide plakortin; specific 4-HNE binding sites on the protein were identified by mass spectrometry, suggesting functional modification of this protein by lipid peroxidation products.","method":"Mass spectrometry identification of 4-HNE protein adducts after plakortin treatment","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (MS identification of adducts); no direct functional validation of the modification's consequence on dynein activity.","pmids":["26459031"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0718000, a putative dynein heavy chain in P. falciparum, has an ortholog in P. yoelii (DHC3) that localizes to subpellicular microtubules in ookinetes and drives Rab11A/Rab11B-labeled cargo transport necessary for apical organelle assembly and ookinete morphogenesis; the P. falciparum protein itself has been identified as a target of oxidative lipid peroxidation adducts (4-HNE) during drug-induced stress, but its precise molecular mechanism remains poorly characterized."},"narrative":{"mechanistic_narrative":"PF3D7_0718000 is a putative dynein heavy chain of P. falciparum whose direct molecular characterization in this species is limited; the corpus identifies it as a target of oxidative lipid peroxidation, forming 4-HNE conjugates at defined sites in response to endoperoxide (plakortin)-induced oxidative stress [PMID:26459031]. The functional consequence of this modification on the protein's activity has not been characterized in the available corpus. In P. yoelii, a putative dynein heavy chain (DHC3) that may correspond to this protein localizes to subpellicular microtubules and drives Rab11A/Rab11B-labeled cargo transport required for apical organelle assembly, ookinete morphogenesis, gliding, and mosquito infection [PMID:39366980]; whether PF3D7_0718000 is the direct ortholog of DHC3 and shares this role has not been established for the P. falciparum protein itself.","teleology":[{"year":2015,"claim":"To ask whether the P. falciparum dynein heavy chain-like protein is a molecular target of antimalarial oxidative stress, the protein was shown to form covalent 4-HNE lipid-peroxidation adducts at defined sites after plakortin treatment, establishing it as a modified target during endoperoxide-induced oxidative damage.","evidence":"Mass spectrometry identification of 4-HNE protein adducts after plakortin treatment in P. falciparum","pmids":["26459031"],"confidence":"Low","gaps":["Single method (MS adduct identification) with no functional validation of the modification's effect on dynein activity","No demonstration that adduct formation alters motility, cargo transport, or parasite viability","Does not establish the protein's normal cellular function in P. falciparum"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"To determine the cellular role of a putative dynein heavy chain in Plasmodium morphogenesis, the P. yoelii ortholog DHC3 was shown to localize to subpellicular microtubules and to transport Rab11A/Rab11B-labeled cargo required for apical organelle formation and ookinete development, framing this dynein as a microtubule motor for polarized intracellular transport.","evidence":"Gene disruption, live imaging/localization, and co-immunoprecipitation of Rab11A/Rab11B with DHC3 in P. yoelii ookinetes","pmids":["39366980"],"confidence":"Medium","gaps":["Demonstrated in P. yoelii DHC3, not in PF3D7_0718000; orthology to the P. falciparum protein is not established","Direct microtubule-based motor activity not reconstituted biochemically","Whether PF3D7_0718000 performs the same transport function in P. falciparum is untested"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"Whether PF3D7_0718000 itself functions as a subpellicular microtubule dynein motor in P. falciparum, and whether its 4-HNE modification alters that activity, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct localization or functional assay of PF3D7_0718000 in P. falciparum","Ortholog relationship between PF3D7_0718000 and P. yoelii DHC3 not confirmed","No link established between the 4-HNE adduction and any motor or transport phenotype"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAB11A (P. YOELII DHC3)","RAB11B (P. YOELII DHC3)"],"other_free_text":["Identified as a target of 4-HNE lipid-peroxidation adduct formation under plakortin-induced oxidative stress in P. falciparum [#1]","Findings on subpellicular microtubule localization and Rab11A/Rab11B-dependent cargo transport derive from the P. yoelii ortholog DHC3, not directly from PF3D7_0718000 [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26459031","id":"PMC_26459031","title":"Oxidative stress-mediated antimalarial activity of plakortin, a natural endoperoxide from the tropical sponge Plakortis simplex.","date":"2015","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26459031","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["dynein heavy chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39366980","id":"PMC_39366980","title":"A subpellicular microtubule dynein transport machinery regulates ookinete morphogenesis for mosquito transmission of Plasmodium yoelii.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39366980","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["dynein heavy chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33228734","id":"PMC_33228734","title":"Definition of constitutive and stage-enriched promoters in the rodent malaria parasite, Plasmodium yoelii.","date":"2020","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/33228734","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["dynein heavy chain"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4414,"output_tokens":821,"usd":0.012778,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5416,"output_tokens":1674,"usd":0.034465,"stage2_stop_reason":"end_turn"},"total_usd":0.047243,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. yoelii ookinetes, DHC3 (a putative dynein heavy chain) localizes to subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection, and defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, functioning as receptors for cargoes driven by the SPMT-dynein motor.\",\n      \"method\": \"Genetic disruption (KO), live imaging/localization, co-immunoprecipitation (Rab11A/Rab11B interaction with DHC3), phenotypic analysis of ookinete morphogenesis and mosquito infection\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction (Co-IP with Rab11A/B), KO with defined cellular phenotype, direct localization; single lab, but multiple orthogonal methods. Note: this paper studies DHC3 in P. yoelii; PF3D7_0718000 is the P. falciparum putative dynein heavy chain and may or may not be the direct ortholog of DHC3.\",\n      \"pmids\": [\"39366980\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In P. falciparum, the dynein heavy chain-like protein forms 4-HNE (4-hydroxynonenal) conjugates in response to oxidative stress induced by the endoperoxide plakortin; specific 4-HNE binding sites on the protein were identified by mass spectrometry, suggesting functional modification of this protein by lipid peroxidation products.\",\n      \"method\": \"Mass spectrometry identification of 4-HNE protein adducts after plakortin treatment\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (MS identification of adducts); no direct functional validation of the modification's consequence on dynein activity.\",\n      \"pmids\": [\"26459031\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0718000, a putative dynein heavy chain in P. falciparum, has an ortholog in P. yoelii (DHC3) that localizes to subpellicular microtubules in ookinetes and drives Rab11A/Rab11B-labeled cargo transport necessary for apical organelle assembly and ookinete morphogenesis; the P. falciparum protein itself has been identified as a target of oxidative lipid peroxidation adducts (4-HNE) during drug-induced stress, but its precise molecular mechanism remains poorly characterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0718000 is a putative dynein heavy chain of P. falciparum whose direct molecular characterization in this species is limited; the corpus identifies it as a target of oxidative lipid peroxidation, forming 4-HNE conjugates at defined sites in response to endoperoxide (plakortin)-induced oxidative stress [#1]. The functional consequence of this modification on the protein's activity has not been characterized in the available corpus. In P. yoelii, a putative dynein heavy chain (DHC3) that may correspond to this protein localizes to subpellicular microtubules and drives Rab11A/Rab11B-labeled cargo transport required for apical organelle assembly, ookinete morphogenesis, gliding, and mosquito infection [#0]; whether PF3D7_0718000 is the direct ortholog of DHC3 and shares this role has not been established for the P. falciparum protein itself.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"To ask whether the P. falciparum dynein heavy chain-like protein is a molecular target of antimalarial oxidative stress, the protein was shown to form covalent 4-HNE lipid-peroxidation adducts at defined sites after plakortin treatment, establishing it as a modified target during endoperoxide-induced oxidative damage.\",\n      \"evidence\": \"Mass spectrometry identification of 4-HNE protein adducts after plakortin treatment in P. falciparum\",\n      \"pmids\": [\"26459031\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (MS adduct identification) with no functional validation of the modification's effect on dynein activity\",\n        \"No demonstration that adduct formation alters motility, cargo transport, or parasite viability\",\n        \"Does not establish the protein's normal cellular function in P. falciparum\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To determine the cellular role of a putative dynein heavy chain in Plasmodium morphogenesis, the P. yoelii ortholog DHC3 was shown to localize to subpellicular microtubules and to transport Rab11A/Rab11B-labeled cargo required for apical organelle formation and ookinete development, framing this dynein as a microtubule motor for polarized intracellular transport.\",\n      \"evidence\": \"Gene disruption, live imaging/localization, and co-immunoprecipitation of Rab11A/Rab11B with DHC3 in P. yoelii ookinetes\",\n      \"pmids\": [\"39366980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Demonstrated in P. yoelii DHC3, not in PF3D7_0718000; orthology to the P. falciparum protein is not established\",\n        \"Direct microtubule-based motor activity not reconstituted biochemically\",\n        \"Whether PF3D7_0718000 performs the same transport function in P. falciparum is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0718000 itself functions as a subpellicular microtubule dynein motor in P. falciparum, and whether its 4-HNE modification alters that activity, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct localization or functional assay of PF3D7_0718000 in P. falciparum\",\n        \"Ortholog relationship between PF3D7_0718000 and P. yoelii DHC3 not confirmed\",\n        \"No link established between the 4-HNE adduction and any motor or transport phenotype\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003777\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Rab11A (P. yoelii DHC3)\", \"Rab11B (P. yoelii DHC3)\"],\n    \"other_free_text\": [\n      \"Identified as a target of 4-HNE lipid-peroxidation adduct formation under plakortin-induced oxidative stress in P. falciparum [#1]\",\n      \"Findings on subpellicular microtubule localization and Rab11A/Rab11B-dependent cargo transport derive from the P. yoelii ortholog DHC3, not directly from PF3D7_0718000 [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0718000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_1320600, PF3D7_1340700). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0718000","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0615700","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0313000","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}