{"gene":"PF3D7_1023100","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2024,"finding":"In P. yoelii ookinetes, DHC3 (a putative dynein heavy chain) localizes at subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; its disruption impairs ookinete development, shape, and gliding, causes defective formation or localization of apical organelles and structures, and leads to failure in mosquito infection. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, suggesting they function as receptors for cargoes transported by the SPMT-dynein motor.","method":"Genetic disruption (knockout), fluorescence localization, co-immunoprecipitation/interaction assays, phenotypic analysis of ookinete morphogenesis and mosquito infection","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction data and KO phenotype with defined cellular readout, single lab, multiple orthogonal methods; however, this is a P. yoelii ortholog (DHC3) and its identity as the exact PF3D7_1023100 ortholog is not explicitly confirmed in the abstract","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 for 4-HNE on this protein were identified by mass spectrometry, implicating it as a target of lipid peroxidation products generated by peroxide-based antimalarials.","method":"Mass spectrometry identification of 4-HNE protein conjugates in plakortin-treated P. falciparum","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single MS identification of a covalent adduct, no functional follow-up on the dynein heavy chain specifically, single lab, single method","pmids":["26459031"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1023100 encodes a putative dynein heavy chain; its P. yoelii ortholog (DHC3) localizes to subpellicular microtubules in ookinetes, drives Rab11A/B-cargo transport required for apical organelle assembly and ookinete morphogenesis, and the P. falciparum protein is susceptible to covalent modification by lipid peroxidation products (4-HNE) generated by peroxide-based antimalarials."},"narrative":{"mechanistic_narrative":"PF3D7_1023100 is a putative dynein heavy chain implicated in microtubule-based intracellular transport during Plasmodium morphogenesis. The direct evidence for its cellular role derives from its P. yoelii ortholog DHC3, which localizes to subpellicular microtubules throughout ookinete development and, when disrupted, produces defective ookinete shape, gliding, and apical organelle formation with consequent failure of mosquito infection; at these microtubules DHC3 engages Rab11A and Rab11B in a DHC3-dependent manner, positioning these Rab GTPases as cargo receptors for a subpellicular microtubule-dynein transport motor [PMID:39366980]. In P. falciparum, the protein itself is subject to covalent modification by 4-hydroxynonenal upon peroxide-antimalarial-induced oxidative stress, with specific 4-HNE adduct sites mapped by mass spectrometry [PMID:26459031]. Beyond these findings, the enzymology, structure, and native complex composition of the P. falciparum protein have not been characterized in the available corpus, and the P. falciparum functional role rests on inference from the P. yoelii ortholog.","teleology":[{"year":2015,"claim":"The question of whether the P. falciparum dynein heavy chain is a molecular target of peroxide-based antimalarials was addressed by showing it is covalently modified by a lipid peroxidation product, linking it to oxidative drug action.","evidence":"Mass spectrometry identification of 4-HNE protein conjugates and adduct sites in plakortin-treated P. falciparum","pmids":["26459031"],"confidence":"Low","gaps":["Single MS identification of a covalent adduct with no functional follow-up on the dynein heavy chain specifically","Whether 4-HNE modification alters motor activity or contributes to drug killing is untested","No structural or biochemical characterization of the protein accompanies the adduct mapping"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"The cellular function of the dynein heavy chain was resolved in the P. yoelii ortholog DHC3, establishing it as a subpellicular microtubule motor that transports Rab11-associated cargo required for apical organelle assembly and ookinete morphogenesis.","evidence":"Genetic knockout, fluorescence localization, co-immunoprecipitation, and phenotypic analysis of ookinete morphogenesis and mosquito infection in P. yoelii","pmids":["39366980"],"confidence":"Medium","gaps":["Findings are in the P. yoelii ortholog DHC3; the exact orthology to P. falciparum PF3D7_1023100 is not explicitly confirmed","Motor activity and directionality were not reconstituted biochemically","The identity of the transported cargoes downstream of Rab11A/B receptors is not defined"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"Whether the P. falciparum protein itself performs the subpellicular microtubule transport function inferred from P. yoelii DHC3, and how its 4-HNE modification relates to that function, remains unresolved.","evidence":"No direct functional characterization of PF3D7_1023100 in P. falciparum exists in the corpus","pmids":[],"confidence":"Medium","gaps":["No P. falciparum knockout or localization data for PF3D7_1023100","No structural model or reconstituted motor activity","No demonstration that the 4-HNE-modified protein is the same functional entity as the P. yoelii ortholog"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAB11A (P. YOELII, VIA DHC3 ORTHOLOG) [#0]","RAB11B (P. YOELII, VIA DHC3 ORTHOLOG) [#0]"],"other_free_text":["Cellular function is established for the P. yoelii ortholog DHC3, not directly for P. falciparum PF3D7_1023100 [#0].","In P. yoelii, DHC3 disruption impairs ookinete development, shape, gliding, apical organelle formation, and mosquito infection [#0].","In P. falciparum, the protein forms covalent 4-hydroxynonenal (4-HNE) conjugates at mapped sites under peroxide-antimalarial-induced oxidative stress, implicating it as a target of lipid peroxidation products [#1]."]}},"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":775,"usd":0.012434,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5357,"output_tokens":1852,"usd":0.036542,"stage2_stop_reason":"end_turn"},"total_usd":0.048976,"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 at subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; its disruption impairs ookinete development, shape, and gliding, causes defective formation or localization of apical organelles and structures, and leads to failure in mosquito infection. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, suggesting they function as receptors for cargoes transported by the SPMT-dynein motor.\",\n      \"method\": \"Genetic disruption (knockout), fluorescence localization, co-immunoprecipitation/interaction assays, phenotypic analysis of ookinete morphogenesis and mosquito infection\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction data and KO phenotype with defined cellular readout, single lab, multiple orthogonal methods; however, this is a P. yoelii ortholog (DHC3) and its identity as the exact PF3D7_1023100 ortholog is not explicitly confirmed in the abstract\",\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 for 4-HNE on this protein were identified by mass spectrometry, implicating it as a target of lipid peroxidation products generated by peroxide-based antimalarials.\",\n      \"method\": \"Mass spectrometry identification of 4-HNE protein conjugates in plakortin-treated P. falciparum\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single MS identification of a covalent adduct, no functional follow-up on the dynein heavy chain specifically, single lab, single method\",\n      \"pmids\": [\"26459031\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1023100 encodes a putative dynein heavy chain; its P. yoelii ortholog (DHC3) localizes to subpellicular microtubules in ookinetes, drives Rab11A/B-cargo transport required for apical organelle assembly and ookinete morphogenesis, and the P. falciparum protein is susceptible to covalent modification by lipid peroxidation products (4-HNE) generated by peroxide-based antimalarials.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1023100 is a putative dynein heavy chain implicated in microtubule-based intracellular transport during Plasmodium morphogenesis. The direct evidence for its cellular role derives from its P. yoelii ortholog DHC3, which localizes to subpellicular microtubules throughout ookinete development and, when disrupted, produces defective ookinete shape, gliding, and apical organelle formation with consequent failure of mosquito infection; at these microtubules DHC3 engages Rab11A and Rab11B in a DHC3-dependent manner, positioning these Rab GTPases as cargo receptors for a subpellicular microtubule-dynein transport motor [#0]. In P. falciparum, the protein itself is subject to covalent modification by 4-hydroxynonenal upon peroxide-antimalarial-induced oxidative stress, with specific 4-HNE adduct sites mapped by mass spectrometry [#1]. Beyond these findings, the enzymology, structure, and native complex composition of the P. falciparum protein have not been characterized in the available corpus, and the P. falciparum functional role rests on inference from the P. yoelii ortholog.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The question of whether the P. falciparum dynein heavy chain is a molecular target of peroxide-based antimalarials was addressed by showing it is covalently modified by a lipid peroxidation product, linking it to oxidative drug action.\",\n      \"evidence\": \"Mass spectrometry identification of 4-HNE protein conjugates and adduct sites in plakortin-treated P. falciparum\",\n      \"pmids\": [\"26459031\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single MS identification of a covalent adduct with no functional follow-up on the dynein heavy chain specifically\",\n        \"Whether 4-HNE modification alters motor activity or contributes to drug killing is untested\",\n        \"No structural or biochemical characterization of the protein accompanies the adduct mapping\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The cellular function of the dynein heavy chain was resolved in the P. yoelii ortholog DHC3, establishing it as a subpellicular microtubule motor that transports Rab11-associated cargo required for apical organelle assembly and ookinete morphogenesis.\",\n      \"evidence\": \"Genetic knockout, fluorescence localization, co-immunoprecipitation, and phenotypic analysis of ookinete morphogenesis and mosquito infection in P. yoelii\",\n      \"pmids\": [\"39366980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Findings are in the P. yoelii ortholog DHC3; the exact orthology to P. falciparum PF3D7_1023100 is not explicitly confirmed\",\n        \"Motor activity and directionality were not reconstituted biochemically\",\n        \"The identity of the transported cargoes downstream of Rab11A/B receptors is not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the P. falciparum protein itself performs the subpellicular microtubule transport function inferred from P. yoelii DHC3, and how its 4-HNE modification relates to that function, remains unresolved.\",\n      \"evidence\": \"No direct functional characterization of PF3D7_1023100 in P. falciparum exists in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No P. falciparum knockout or localization data for PF3D7_1023100\",\n        \"No structural model or reconstituted motor activity\",\n        \"No demonstration that the 4-HNE-modified protein is the same functional entity as the P. yoelii ortholog\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\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:0047496\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Rab11A (P. yoelii, via DHC3 ortholog) [#0]\",\n      \"Rab11B (P. yoelii, via DHC3 ortholog) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Cellular function is established for the P. yoelii ortholog DHC3, not directly for P. falciparum PF3D7_1023100 [#0].\",\n      \"In P. yoelii, DHC3 disruption impairs ookinete development, shape, gliding, apical organelle formation, and mosquito infection [#0].\",\n      \"In P. falciparum, the protein forms covalent 4-hydroxynonenal (4-HNE) conjugates at mapped sites under peroxide-antimalarial-induced oxidative stress, implicating it as a target of lipid peroxidation products [#1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1023100","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_1023100","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0507300","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0607600","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}