{"gene":"PF3D7_1202300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2024,"finding":"In P. yoelii ookinetes, DHC3 (a dynein heavy chain) localizes to subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; its disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection. DHC3-deficient ookinetes show defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, identifying them as receptors for cargoes driven by the SPMT-dynein motor.","method":"Genetic disruption (KO), fluorescence localization, co-immunoprecipitation/interaction assays, ookinete morphogenesis and gliding assays, mosquito infection assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction data, clean KO with defined cellular phenotype, direct localization; single lab but multiple orthogonal methods. Note: this paper studies P. yoelii DHC3; its correspondence to PF3D7_1202300 is inferred from the gene family screen context but not explicitly confirmed.","pmids":["39366980"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2015,"finding":"In P. falciparum, the dynein heavy chain-like protein forms 4-hydroxynonenal (4-HNE) conjugates upon plakortin treatment, with specific binding sites identified by mass spectrometry, implicating it as a target of oxidative stress-mediated damage during peroxide-based antimalarial activity.","method":"Mass spectrometry identification of 4-HNE-protein conjugates","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single mass spectrometry identification with no functional follow-up on this specific protein; no gene-level validation that the protein is PF3D7_1202300 specifically.","pmids":["26459031"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1202300 encodes a putative dynein heavy chain; in the related species P. yoelii, the ortholog DHC3 localizes to subpellicular microtubules in ookinetes and drives minus-end-directed transport of Rab11A/B-labeled cargoes required for apical organelle assembly and ookinete morphogenesis, while in P. falciparum the protein has been identified as a target of oxidative adduction by antimalarial peroxides, but no direct functional characterization of PF3D7_1202300 itself has been reported."},"narrative":{"mechanistic_narrative":"PF3D7_1202300 is annotated as a putative dynein heavy chain, and direct functional characterization of the P. falciparum protein itself is limited in the available corpus. The strongest mechanistic evidence derives from the P. yoelii ortholog DHC3, which localizes to subpellicular microtubules throughout ookinete morphogenesis and, when disrupted, impairs ookinete development, shape, gliding, and mosquito infection; DHC3-deficient ookinetes show defective formation or localization of apical organelles [PMID:39366980]. In P. yoelii, Rab11A and Rab11B interact with DHC3 at subpellicular microtubules in a DHC3-dependent manner, identifying them as cargo receptors for this microtubule-associated dynein motor [PMID:39366980]. In P. falciparum, a dynein heavy chain-like protein has been identified only as a target of oxidative adduction, forming 4-hydroxynonenal conjugates upon plakortin treatment [PMID:26459031]. Beyond the P. yoelii ortholog data [PMID:39366980] and this oxidative-damage identification [PMID:26459031], no direct functional characterization of PF3D7_1202300 has been reported in the available corpus.","teleology":[{"year":2015,"claim":"The question of whether a dynein heavy chain-like protein participates in the response to peroxide antimalarials was addressed by identifying it as a target of oxidative adduction.","evidence":"Mass spectrometry identification of 4-HNE-protein conjugates in plakortin-treated P. falciparum","pmids":["26459031"],"confidence":"Low","gaps":["Gene-level validation that the adducted protein is PF3D7_1202300 specifically is absent","No functional consequence of the adduction was tested","No connection to the protein's normal cellular role was established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"The cellular function of this dynein heavy chain was defined in the ortholog DHC3, establishing it as a subpellicular microtubule-associated motor required for ookinete morphogenesis and apical organelle organization.","evidence":"Genetic KO, fluorescence localization, co-immunoprecipitation, and ookinete/mosquito infection assays in P. yoelii","pmids":["39366980"],"confidence":"Medium","gaps":["Correspondence between P. yoelii DHC3 and PF3D7_1202300 is inferred, not experimentally confirmed","Minus-end-directed motor activity and direct cargo transport were not reconstituted biochemically","No functional characterization was performed in P. falciparum itself"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"Whether PF3D7_1202300 in P. falciparum performs the microtubule-associated dynein transport role established for the P. yoelii ortholog remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct genetic disruption or localization of PF3D7_1202300 in P. falciparum has been reported","Rab11A/B interaction has not been tested for the P. falciparum protein","The identity linking the ortholog studies to PF3D7_1202300 is unconfirmed"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAB11A (P. YOELII ORTHOLOG CONTEXT) [#0]","RAB11B (P. YOELII ORTHOLOG CONTEXT) [#0]"],"other_free_text":["Ortholog DHC3 in P. yoelii is required for ookinete development, shape, gliding, and mosquito infection [#0]","DHC3-deficient ookinetes show defective apical organelle formation/localization [#0]","In P. falciparum, a dynein heavy chain-like protein forms 4-HNE conjugates upon plakortin treatment, implicating it as a target of peroxide-based antimalarial oxidative damage [#1]","Correspondence between the P. yoelii DHC3 studies and PF3D7_1202300 is inferred from gene-family context, not explicitly confirmed [#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":789,"usd":0.012538,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5376,"output_tokens":1696,"usd":0.03464,"stage2_stop_reason":"end_turn"},"total_usd":0.047178,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","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 to subpellicular microtubules (SPMTs) throughout ookinete morphogenesis; its disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection. DHC3-deficient ookinetes show defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, identifying them as receptors for cargoes driven by the SPMT-dynein motor.\",\n      \"method\": \"Genetic disruption (KO), fluorescence localization, co-immunoprecipitation/interaction assays, ookinete morphogenesis and gliding assays, mosquito infection assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction data, clean KO with defined cellular phenotype, direct localization; single lab but multiple orthogonal methods. Note: this paper studies P. yoelii DHC3; its correspondence to PF3D7_1202300 is inferred from the gene family screen context but not explicitly confirmed.\",\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-hydroxynonenal (4-HNE) conjugates upon plakortin treatment, with specific binding sites identified by mass spectrometry, implicating it as a target of oxidative stress-mediated damage during peroxide-based antimalarial activity.\",\n      \"method\": \"Mass spectrometry identification of 4-HNE-protein conjugates\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single mass spectrometry identification with no functional follow-up on this specific protein; no gene-level validation that the protein is PF3D7_1202300 specifically.\",\n      \"pmids\": [\"26459031\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1202300 encodes a putative dynein heavy chain; in the related species P. yoelii, the ortholog DHC3 localizes to subpellicular microtubules in ookinetes and drives minus-end-directed transport of Rab11A/B-labeled cargoes required for apical organelle assembly and ookinete morphogenesis, while in P. falciparum the protein has been identified as a target of oxidative adduction by antimalarial peroxides, but no direct functional characterization of PF3D7_1202300 itself has been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1202300 is annotated as a putative dynein heavy chain, and direct functional characterization of the P. falciparum protein itself is limited in the available corpus. The strongest mechanistic evidence derives from the P. yoelii ortholog DHC3, which localizes to subpellicular microtubules throughout ookinete morphogenesis and, when disrupted, impairs ookinete development, shape, gliding, and mosquito infection; DHC3-deficient ookinetes show defective formation or localization of apical organelles [#0]. In P. yoelii, Rab11A and Rab11B interact with DHC3 at subpellicular microtubules in a DHC3-dependent manner, identifying them as cargo receptors for this microtubule-associated dynein motor [#0]. In P. falciparum, a dynein heavy chain-like protein has been identified only as a target of oxidative adduction, forming 4-hydroxynonenal conjugates upon plakortin treatment [#1]. Beyond the P. yoelii ortholog data [#0] and this oxidative-damage identification [#1], no direct functional characterization of PF3D7_1202300 has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The question of whether a dynein heavy chain-like protein participates in the response to peroxide antimalarials was addressed by identifying it as a target of oxidative adduction.\",\n      \"evidence\": \"Mass spectrometry identification of 4-HNE-protein conjugates in plakortin-treated P. falciparum\",\n      \"pmids\": [\"26459031\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Gene-level validation that the adducted protein is PF3D7_1202300 specifically is absent\",\n        \"No functional consequence of the adduction was tested\",\n        \"No connection to the protein's normal cellular role was established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The cellular function of this dynein heavy chain was defined in the ortholog DHC3, establishing it as a subpellicular microtubule-associated motor required for ookinete morphogenesis and apical organelle organization.\",\n      \"evidence\": \"Genetic KO, fluorescence localization, co-immunoprecipitation, and ookinete/mosquito infection assays in P. yoelii\",\n      \"pmids\": [\"39366980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Correspondence between P. yoelii DHC3 and PF3D7_1202300 is inferred, not experimentally confirmed\",\n        \"Minus-end-directed motor activity and direct cargo transport were not reconstituted biochemically\",\n        \"No functional characterization was performed in P. falciparum itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1202300 in P. falciparum performs the microtubule-associated dynein transport role established for the P. yoelii ortholog remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct genetic disruption or localization of PF3D7_1202300 in P. falciparum has been reported\",\n        \"Rab11A/B interaction has not been tested for the P. falciparum protein\",\n        \"The identity linking the ortholog studies to PF3D7_1202300 is unconfirmed\"\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:0071973\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Rab11A (P. yoelii ortholog context) [#0]\", \"Rab11B (P. yoelii ortholog context) [#0]\"],\n    \"other_free_text\": [\n      \"Ortholog DHC3 in P. yoelii is required for ookinete development, shape, gliding, and mosquito infection [#0]\",\n      \"DHC3-deficient ookinetes show defective apical organelle formation/localization [#0]\",\n      \"In P. falciparum, a dynein heavy chain-like protein forms 4-HNE conjugates upon plakortin treatment, implicating it as a target of peroxide-based antimalarial oxidative damage [#1]\",\n      \"Correspondence between the P. yoelii DHC3 studies and PF3D7_1202300 is inferred from gene-family context, not explicitly confirmed [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1202300","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_1202300","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0601200","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1302200","name":null,"product":"dynein heavy chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}