{"gene":"PF3D7_1008700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2005,"finding":"Radiolabelled trifluralin (a dinitroaniline herbicide) interacted directly with purified, recombinant P. falciparum tubulin (including beta-tubulin) but to a much lesser extent with bovine tubulins, indicating that P. falciparum beta-tubulin contains a dinitroaniline/phosphorothioamidate-binding site not conserved in humans. Treatment with trifluralin and oryzalin blocked schizogony, inhibited mitotic division, and caused accumulation of abnormal microtubular structures.","method":"Radiolabelled ligand-binding assay with purified recombinant parasite tubulin; in vitro parasite growth inhibition assay; microscopy of microtubular structures","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct radiolabelled binding to recombinant protein plus cellular phenotype, single lab, two orthogonal methods","pmids":["16406111"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1990,"finding":"The P. falciparum beta-tubulin gene was isolated and fully sequenced at the genomic level; the deduced polypeptide is 445 amino acids long, shares 88% amino acid homology with chicken brain beta-tubulin, contains two introns (362 bp and 163 bp), and is unlinked from the alpha-tubulin gene. Northern blot analysis detected three beta-tubulin transcripts (3.6 kb, 2.9 kb, 2.0 kb) in blood-stage parasites.","method":"Genomic and cDNA library screening with oligonucleotide probe; DNA sequencing; Northern blot analysis","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct sequencing and Northern blot, single lab, two orthogonal methods establishing gene structure and expression","pmids":["2181306"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"P. falciparum apicortin (PfApicortin) interacts with both P. falciparum α-tubulin-I and β-tubulin in vitro. Disruption of the PfApicortin–tubulin interaction with the p25-domain-binding drug Tamoxifen inhibited growth and progression of blood-stage P. falciparum, establishing that PfApicortin–β-tubulin interaction is required for parasite survival.","method":"In silico docking and in vitro binding studies; small-molecule (Tamoxifen) disruption of protein–protein interaction; P. falciparum blood-stage growth assay","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — in vitro binding and pharmacological disruption, single lab, no genetic validation of the specific interaction","pmids":["33633135"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum beta-tubulin (PF3D7_1008700) is a 445-amino-acid cytoskeletal protein required for mitotic division during schizogony; it contains a dinitroaniline-binding site distinct from mammalian tubulin, is targeted by herbicidal compounds that block parasite division, and interacts with the Apicomplexan-specific protein apicortin in a manner important for blood-stage parasite survival."},"narrative":{"mechanistic_narrative":"PF3D7_1008700 encodes P. falciparum beta-tubulin, a 445-amino-acid cytoskeletal protein whose gene contains two introns, is unlinked from the alpha-tubulin locus, and is transcribed as multiple beta-tubulin messages in blood-stage parasites [PMID:2181306]. As a microtubule component, it is required for the mitotic divisions of schizogony: purified recombinant parasite beta-tubulin directly binds the dinitroaniline herbicide trifluralin through a site poorly conserved in mammalian (bovine) tubulin, and dinitroaniline treatment blocks schizogony, arrests mitotic division, and produces abnormal microtubular structures [PMID:16406111]. This parasite-selective drug-binding site distinguishes it from human tubulin [PMID:16406111]. Beta-tubulin also engages the Apicomplexan protein apicortin in vitro, an interaction whose pharmacological disruption impairs blood-stage growth [PMID:33633135].","teleology":[{"year":1990,"claim":"Establishing the gene structure and expression was the necessary first step to define P. falciparum beta-tubulin as a discrete, characterizable cytoskeletal gene distinct from its alpha-tubulin counterpart.","evidence":"Genomic/cDNA library screening, DNA sequencing, and Northern blot of blood-stage parasites","pmids":["2181306"],"confidence":"Medium","gaps":["The identity and significance of the three distinct transcript sizes were not resolved","No protein-level localization or function established at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Whether beta-tubulin harbors a parasite-selective drug target was answered by showing direct dinitroaniline binding to parasite but not mammalian tubulin, coupled to a mitotic-arrest phenotype, defining beta-tubulin's role in schizogony and its exploitable pharmacology.","evidence":"Radiolabelled trifluralin binding to purified recombinant parasite tubulin, in vitro growth inhibition, and microscopy of microtubular structures","pmids":["16406111"],"confidence":"Medium","gaps":["The precise residues forming the dinitroaniline-binding site were not mapped","Binding was measured on total recombinant tubulin, not the beta-subunit in isolation with defined stoichiometry"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether beta-tubulin participates in a defined protein–protein interaction relevant to survival was addressed by identifying apicortin as an in vitro binding partner whose disruption impairs blood-stage growth.","evidence":"In silico docking with in vitro binding, Tamoxifen-mediated interaction disruption, and blood-stage growth assay","pmids":["33633135"],"confidence":"Low","gaps":["No genetic validation of the specific apicortin–beta-tubulin interaction; relies on pharmacology and in vitro binding","Tamoxifen's growth effect cannot be attributed solely to this interaction","Structural details and cellular localization of the complex not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Direct genetic evidence for the essentiality and in vivo function of PF3D7_1008700, and a residue-level structure of its parasite-selective drug-binding site, remain to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No knockout/conditional-knockdown data for the gene itself","No high-resolution structure of the dinitroaniline-binding site","Contribution of individual transcripts and any stage specificity unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFAPICORTIN (PFAPICORTIN–BETA-TUBULIN INTERACTION, IN VITRO) [#2]","P. FALCIPARUM ALPHA-TUBULIN (AS TUBULIN HETERODIMER CONTEXT) [#1, #2]"],"other_free_text":["445-amino-acid polypeptide; gene contains two introns and is unlinked from alpha-tubulin; three blood-stage transcripts detected [#1]","Contains a dinitroaniline/phosphorothioamidate-binding site not conserved in mammalian (bovine) tubulin; targeted by trifluralin and oryzalin [#0]","Dinitroaniline treatment blocks schizogony and mitotic division, producing abnormal microtubular structures [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16406111","id":"PMC_16406111","title":"Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/16406111","citation_count":69,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2181306","id":"PMC_2181306","title":"Isolation of alpha- and beta-tubulin genes of Plasmodium falciparum using a single oligonucleotide probe.","date":"1990","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2181306","citation_count":21,"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":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4045,"output_tokens":1040,"usd":0.013867,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5746,"output_tokens":2001,"usd":0.039378,"stage2_stop_reason":"end_turn"},"total_usd":0.053245,"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\": 2005,\n      \"finding\": \"Radiolabelled trifluralin (a dinitroaniline herbicide) interacted directly with purified, recombinant P. falciparum tubulin (including beta-tubulin) but to a much lesser extent with bovine tubulins, indicating that P. falciparum beta-tubulin contains a dinitroaniline/phosphorothioamidate-binding site not conserved in humans. Treatment with trifluralin and oryzalin blocked schizogony, inhibited mitotic division, and caused accumulation of abnormal microtubular structures.\",\n      \"method\": \"Radiolabelled ligand-binding assay with purified recombinant parasite tubulin; in vitro parasite growth inhibition assay; microscopy of microtubular structures\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct radiolabelled binding to recombinant protein plus cellular phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"16406111\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"The P. falciparum beta-tubulin gene was isolated and fully sequenced at the genomic level; the deduced polypeptide is 445 amino acids long, shares 88% amino acid homology with chicken brain beta-tubulin, contains two introns (362 bp and 163 bp), and is unlinked from the alpha-tubulin gene. Northern blot analysis detected three beta-tubulin transcripts (3.6 kb, 2.9 kb, 2.0 kb) in blood-stage parasites.\",\n      \"method\": \"Genomic and cDNA library screening with oligonucleotide probe; DNA sequencing; Northern blot analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct sequencing and Northern blot, single lab, two orthogonal methods establishing gene structure and expression\",\n      \"pmids\": [\"2181306\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"P. falciparum apicortin (PfApicortin) interacts with both P. falciparum α-tubulin-I and β-tubulin in vitro. Disruption of the PfApicortin–tubulin interaction with the p25-domain-binding drug Tamoxifen inhibited growth and progression of blood-stage P. falciparum, establishing that PfApicortin–β-tubulin interaction is required for parasite survival.\",\n      \"method\": \"In silico docking and in vitro binding studies; small-molecule (Tamoxifen) disruption of protein–protein interaction; P. falciparum blood-stage growth assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — in vitro binding and pharmacological disruption, single lab, no genetic validation of the specific interaction\",\n      \"pmids\": [\"33633135\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum beta-tubulin (PF3D7_1008700) is a 445-amino-acid cytoskeletal protein required for mitotic division during schizogony; it contains a dinitroaniline-binding site distinct from mammalian tubulin, is targeted by herbicidal compounds that block parasite division, and interacts with the Apicomplexan-specific protein apicortin in a manner important for blood-stage parasite survival.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1008700 encodes P. falciparum beta-tubulin, a 445-amino-acid cytoskeletal protein whose gene contains two introns, is unlinked from the alpha-tubulin locus, and is transcribed as multiple beta-tubulin messages in blood-stage parasites [#1]. As a microtubule component, it is required for the mitotic divisions of schizogony: purified recombinant parasite beta-tubulin directly binds the dinitroaniline herbicide trifluralin through a site poorly conserved in mammalian (bovine) tubulin, and dinitroaniline treatment blocks schizogony, arrests mitotic division, and produces abnormal microtubular structures [#0]. This parasite-selective drug-binding site distinguishes it from human tubulin [#0]. Beta-tubulin also engages the Apicomplexan protein apicortin in vitro, an interaction whose pharmacological disruption impairs blood-stage growth [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Establishing the gene structure and expression was the necessary first step to define P. falciparum beta-tubulin as a discrete, characterizable cytoskeletal gene distinct from its alpha-tubulin counterpart.\",\n      \"evidence\": \"Genomic/cDNA library screening, DNA sequencing, and Northern blot of blood-stage parasites\",\n      \"pmids\": [\"2181306\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The identity and significance of the three distinct transcript sizes were not resolved\",\n        \"No protein-level localization or function established at this stage\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Whether beta-tubulin harbors a parasite-selective drug target was answered by showing direct dinitroaniline binding to parasite but not mammalian tubulin, coupled to a mitotic-arrest phenotype, defining beta-tubulin's role in schizogony and its exploitable pharmacology.\",\n      \"evidence\": \"Radiolabelled trifluralin binding to purified recombinant parasite tubulin, in vitro growth inhibition, and microscopy of microtubular structures\",\n      \"pmids\": [\"16406111\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The precise residues forming the dinitroaniline-binding site were not mapped\",\n        \"Binding was measured on total recombinant tubulin, not the beta-subunit in isolation with defined stoichiometry\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether beta-tubulin participates in a defined protein–protein interaction relevant to survival was addressed by identifying apicortin as an in vitro binding partner whose disruption impairs blood-stage growth.\",\n      \"evidence\": \"In silico docking with in vitro binding, Tamoxifen-mediated interaction disruption, and blood-stage growth assay\",\n      \"pmids\": [\"33633135\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic validation of the specific apicortin–beta-tubulin interaction; relies on pharmacology and in vitro binding\",\n        \"Tamoxifen's growth effect cannot be attributed solely to this interaction\",\n        \"Structural details and cellular localization of the complex not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Direct genetic evidence for the essentiality and in vivo function of PF3D7_1008700, and a residue-level structure of its parasite-selective drug-binding site, remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout/conditional-knockdown data for the gene itself\",\n        \"No high-resolution structure of the dinitroaniline-binding site\",\n        \"Contribution of individual transcripts and any stage specificity unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005200\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008144\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000278\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfApicortin (PfApicortin\\u2013beta-tubulin interaction, in vitro) [#2]\",\n      \"P. falciparum alpha-tubulin (as tubulin heterodimer context) [#1, #2]\"\n    ],\n    \"other_free_text\": [\n      \"445-amino-acid polypeptide; gene contains two introns and is unlinked from alpha-tubulin; three blood-stage transcripts detected [#1]\",\n      \"Contains a dinitroaniline/phosphorothioamidate-binding site not conserved in mammalian (bovine) tubulin; targeted by trifluralin and oryzalin [#0]\",\n      \"Dinitroaniline treatment blocks schizogony and mitotic division, producing abnormal microtubular structures [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1008700","name":null,"product":"tubulin beta chain","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1206900","name":null,"product":"tubulin beta chain, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0807700","name":null,"product":"tubulin beta chain, fragment","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}