{"gene":"PF3D7_0729900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2024,"finding":"In P. yoelii ookinetes, DHC3 (a dynein heavy chain) localizes at subpellicular microtubules (SPMTs) throughout ookinete morphogenesis, and its disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection. DHC3-deficient ookinetes display 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 (knockout), live imaging/localization, co-immunoprecipitation (Rab11A/B interaction with DHC3), ookinete morphogenesis and gliding motility assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction data (Co-IP), clean KO with defined cellular phenotype, direct localization; single lab but multiple orthogonal methods. Note: this paper studies DHC3 in P. yoelii; its direct equivalence to PF3D7_0729900 is inferred from the screen of 7 putative DHC proteins but is not explicitly confirmed in P. falciparum.","pmids":["39366980"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2015,"finding":"In P. falciparum, the dynein heavy chain-like protein forms a 4-hydroxynonenal (4-HNE) conjugate upon plakortin-induced oxidative stress; specific binding sites were identified by mass spectrometry, implicating the protein as a target of oxidative damage in the mechanism of action of pro-oxidant antimalarials.","method":"Mass spectrometry identification of 4-HNE protein adducts from plakortin-treated parasites","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single mass spectrometry identification of a covalent adduct, no functional follow-up on the dynein heavy chain specifically, single lab","pmids":["26459031"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0729900 encodes a putative dynein heavy chain; its P. yoelii ortholog DHC3 localizes to subpellicular microtubules in ookinetes, drives Rab11A/B-labeled cargo transport required for apical organelle assembly and ookinete morphogenesis, and in P. falciparum the protein is susceptible to covalent modification by the lipid peroxidation product 4-HNE under pro-oxidant antimalarial treatment."},"narrative":{"mechanistic_narrative":"PF3D7_0729900 is a putative dynein heavy chain whose function in P. falciparum has not been directly characterized in the available corpus; the mechanistic picture rests on its inferred P. yoelii ortholog DHC3. In P. yoelii ookinetes, DHC3 localizes to subpellicular microtubules throughout morphogenesis and acts as a microtubule-associated motor whose disruption impairs ookinete development, shape, and gliding motility, ultimately causing failure of mosquito infection; DHC3-deficient parasites also show defective formation or localization of apical organelles, indicating a role in cargo transport required for apical organelle assembly [PMID:39366980]. Rab11A and Rab11B interact with DHC3 at subpellicular microtubules in a DHC3-dependent manner and serve as receptors for cargoes driven by this motor [PMID:39366980]. In P. falciparum, the dynein heavy chain-like protein is a target of covalent modification by the lipid peroxidation product 4-HNE under plakortin-induced oxidative stress, implicating it as a damage target in the action of pro-oxidant antimalarials [PMID:26459031]. Beyond these findings, no further mechanistic detail for PF3D7_0729900 has been characterized in the available corpus, and its equivalence to P. yoelii DHC3 is inferred rather than experimentally confirmed in P. falciparum.","teleology":[{"year":2015,"claim":"It was unknown which parasite proteins are damaged by pro-oxidant antimalarials; identifying the dynein heavy chain-like protein as a 4-HNE adduct target established it as a candidate effector site of oxidative-stress-based drug action.","evidence":"Mass spectrometry identification of 4-HNE protein adducts from plakortin-treated P. falciparum parasites","pmids":["26459031"],"confidence":"Low","gaps":["Single mass spectrometry identification of a covalent adduct with no functional follow-up on the dynein heavy chain","Whether 4-HNE modification alters the protein's motor activity or localization is unknown","No demonstration that adduct formation contributes causally to parasite killing"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"The cellular role of this dynein heavy chain was undefined; genetic and interaction analysis of the P. yoelii ortholog DHC3 established it as a subpellicular-microtubule motor driving Rab11-dependent cargo transport needed for ookinete morphogenesis and mosquito transmission.","evidence":"Gene knockout, live imaging/localization, Rab11A/B co-immunoprecipitation, and ookinete morphogenesis and gliding assays in P. yoelii","pmids":["39366980"],"confidence":"Medium","gaps":["Direct equivalence of P. yoelii DHC3 to P. falciparum PF3D7_0729900 is inferred from a screen of putative DHC proteins, not experimentally confirmed","The specific cargoes carried downstream of Rab11A/B receptors were not identified","Function in P. falciparum blood or transmission stages was not tested"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"Whether PF3D7_0729900 itself performs the microtubule-associated, Rab11-linked motor functions demonstrated for P. yoelii DHC3 remains to be established directly in P. falciparum.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct localization or knockout of PF3D7_0729900 in P. falciparum in the corpus","Functional consequence of 4-HNE modification on motor activity unresolved","Relationship between the oxidative-damage target and the ookinete transport role is unexplored"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAB11A (P. YOELII DHC3, [#0])","RAB11B (P. YOELII DHC3, [#0])"],"other_free_text":["P. falciparum dynein heavy chain-like protein forms 4-HNE covalent adducts under plakortin-induced oxidative stress [#1]","Equivalence of P. yoelii DHC3 to PF3D7_0729900 is inferred from a screen of putative dynein heavy chains, not confirmed in P. falciparum [#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":801,"usd":0.012629,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5395,"output_tokens":1797,"usd":0.03595,"stage2_stop_reason":"end_turn"},"total_usd":0.048579,"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 dynein heavy chain) localizes at subpellicular microtubules (SPMTs) throughout ookinete morphogenesis, and its disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection. DHC3-deficient ookinetes display 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 (knockout), live imaging/localization, co-immunoprecipitation (Rab11A/B interaction with DHC3), ookinete morphogenesis and gliding motility assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction data (Co-IP), clean KO with defined cellular phenotype, direct localization; single lab but multiple orthogonal methods. Note: this paper studies DHC3 in P. yoelii; its direct equivalence to PF3D7_0729900 is inferred from the screen of 7 putative DHC proteins but is not explicitly confirmed in P. falciparum.\",\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 a 4-hydroxynonenal (4-HNE) conjugate upon plakortin-induced oxidative stress; specific binding sites were identified by mass spectrometry, implicating the protein as a target of oxidative damage in the mechanism of action of pro-oxidant antimalarials.\",\n      \"method\": \"Mass spectrometry identification of 4-HNE protein adducts from plakortin-treated parasites\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single mass spectrometry identification of a covalent adduct, no functional follow-up on the dynein heavy chain specifically, single lab\",\n      \"pmids\": [\"26459031\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0729900 encodes a putative dynein heavy chain; its P. yoelii ortholog DHC3 localizes to subpellicular microtubules in ookinetes, drives Rab11A/B-labeled cargo transport required for apical organelle assembly and ookinete morphogenesis, and in P. falciparum the protein is susceptible to covalent modification by the lipid peroxidation product 4-HNE under pro-oxidant antimalarial treatment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0729900 is a putative dynein heavy chain whose function in P. falciparum has not been directly characterized in the available corpus; the mechanistic picture rests on its inferred P. yoelii ortholog DHC3. In P. yoelii ookinetes, DHC3 localizes to subpellicular microtubules throughout morphogenesis and acts as a microtubule-associated motor whose disruption impairs ookinete development, shape, and gliding motility, ultimately causing failure of mosquito infection; DHC3-deficient parasites also show defective formation or localization of apical organelles, indicating a role in cargo transport required for apical organelle assembly [#0]. Rab11A and Rab11B interact with DHC3 at subpellicular microtubules in a DHC3-dependent manner and serve as receptors for cargoes driven by this motor [#0]. In P. falciparum, the dynein heavy chain-like protein is a target of covalent modification by the lipid peroxidation product 4-HNE under plakortin-induced oxidative stress, implicating it as a damage target in the action of pro-oxidant antimalarials [#1]. Beyond these findings, no further mechanistic detail for PF3D7_0729900 has been characterized in the available corpus, and its equivalence to P. yoelii DHC3 is inferred rather than experimentally confirmed in P. falciparum.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unknown which parasite proteins are damaged by pro-oxidant antimalarials; identifying the dynein heavy chain-like protein as a 4-HNE adduct target established it as a candidate effector site of oxidative-stress-based drug action.\",\n      \"evidence\": \"Mass spectrometry identification of 4-HNE protein adducts from plakortin-treated P. falciparum parasites\",\n      \"pmids\": [\"26459031\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single mass spectrometry identification of a covalent adduct with no functional follow-up on the dynein heavy chain\",\n        \"Whether 4-HNE modification alters the protein's motor activity or localization is unknown\",\n        \"No demonstration that adduct formation contributes causally to parasite killing\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The cellular role of this dynein heavy chain was undefined; genetic and interaction analysis of the P. yoelii ortholog DHC3 established it as a subpellicular-microtubule motor driving Rab11-dependent cargo transport needed for ookinete morphogenesis and mosquito transmission.\",\n      \"evidence\": \"Gene knockout, live imaging/localization, Rab11A/B co-immunoprecipitation, and ookinete morphogenesis and gliding assays in P. yoelii\",\n      \"pmids\": [\"39366980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct equivalence of P. yoelii DHC3 to P. falciparum PF3D7_0729900 is inferred from a screen of putative DHC proteins, not experimentally confirmed\",\n        \"The specific cargoes carried downstream of Rab11A/B receptors were not identified\",\n        \"Function in P. falciparum blood or transmission stages was not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0729900 itself performs the microtubule-associated, Rab11-linked motor functions demonstrated for P. yoelii DHC3 remains to be established directly in P. falciparum.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct localization or knockout of PF3D7_0729900 in P. falciparum in the corpus\",\n        \"Functional consequence of 4-HNE modification on motor activity unresolved\",\n        \"Relationship between the oxidative-damage target and the ookinete transport role is unexplored\"\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:0007018\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Rab11A (P. yoelii DHC3, [#0])\",\n      \"Rab11B (P. yoelii DHC3, [#0])\"\n    ],\n    \"other_free_text\": [\n      \"P. falciparum dynein heavy chain-like protein forms 4-HNE covalent adducts under plakortin-induced oxidative stress [#1]\",\n      \"Equivalence of P. yoelii DHC3 to PF3D7_0729900 is inferred from a screen of putative dynein heavy chains, not confirmed in P. falciparum [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0729900","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_0729900","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0214000","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0214800","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}