{"gene":"PF3D7_1403800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2009,"finding":"MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes, and ookinetes, as determined by direct imaging of the tagged protein.","method":"Fluorescence microscopy / subcellular localization of tagged protein","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiment in the founding characterization paper, replicated in subsequent studies citing the same finding","pmids":["19662167"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"finding":"Gene disruption of MISFIT results in mutant ookinetes with reduced genome content (less than wild-type DNA content) and microneme defects, yet these ookinetes still successfully invade the mosquito midgut epithelium.","method":"Gene disruption / targeted knockout with flow cytometry (DNA content) and electron microscopy (microneme ultrastructure)","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean gene disruption with multiple orthogonal readouts (DNA content, EM ultrastructure, invasion assay) in the founding paper; independently corroborated by multiple subsequent studies","pmids":["19662167"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"finding":"Disruption of MISFIT causes developmental arrest at the ookinete-to-oocyst transition, blocking malaria transmission; the few oocysts that form are smaller than wild-type and fail to complete sporulation.","method":"Gene disruption / targeted knockout with mosquito infection assay and oocyst phenotypic analysis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic loss-of-function with defined cellular phenotype, independently corroborated by multiple subsequent studies citing the same oocyst arrest phenotype","pmids":["19662167"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"finding":"Genetic crosses between misfit mutant parasites and lines deficient in either male or female gametes reveal a strict requirement for a male (paternal) misfit allele, demonstrating that MISFIT exerts a paternal effect on development.","method":"Genetic cross / epistasis using male-gamete-deficient and female-gamete-deficient parasite lines","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic complementation crosses with defined gamete-deficient lines, a rigorous epistasis approach; finding corroborated by independent studies","pmids":["19662167"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"finding":"Disruption of MISFIT alters the transcriptional profiles of putative cell cycle regulators in ookinetes, consistent with a role in cell cycle progression.","method":"Transcriptome analysis of misfit knockout ookinetes","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — transcriptomic readout in a defined genetic mutant, single lab, no direct mechanistic follow-up of the altered transcripts","pmids":["19662167"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"MISFIT is identified as a putative interactor of Aurora-related kinase 2 (ARK2) by interactomic (mass spectrometry) and co-localization studies during sexual proliferation, placing MISFIT in a spindle-associated complex together with EB1 and Myosin-K.","method":"Co-immunoprecipitation / mass spectrometry interactomics and co-localization by fluorescence microscopy","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single co-IP/MS experiment from one lab with co-localization support, but MISFIT is listed as a putative interactor and the interaction was not independently validated by reciprocal pull-down or reconstitution","pmids":["37704606"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"MISFIT (PF3D7_1403800) is a nuclear formin-like protein expressed in male gametocytes that localizes to the nuclei of male gametocytes, zygotes, and ookinetes in Plasmodium berghei; its paternal allele is strictly required for the ookinete-to-oocyst developmental transition, as gene disruption produces ookinetes with reduced genome content and microneme defects that can still invade the midgut but then arrest before oocyst maturation, with altered expression of cell cycle regulators; it also associates as a putative component of an ARK2/EB1/Myosin-K spindle complex during sexual development."},"narrative":{"mechanistic_narrative":"MISFIT (PF3D7_1403800) is a nuclear formin-like protein that governs the ookinete-to-oocyst developmental transition during the mosquito stage of the Plasmodium life cycle, acting as a determinant of malaria transmission [PMID:19662167]. In Plasmodium berghei, MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes, and ookinetes [PMID:19662167], and its function is exerted as a strict paternal (male-allele) effect: genetic crosses with gamete-deficient lines demonstrate that a male misfit allele is required for downstream development [PMID:19662167]. Loss of MISFIT produces ookinetes with reduced genome content and microneme defects that still invade the midgut epithelium but then arrest before oocyst maturation, with the few oocysts that form remaining small and failing to sporulate [PMID:19662167]; disruption also alters the transcript levels of putative cell cycle regulators, consistent with a role in nuclear/cell-cycle control [PMID:19662167]. During sexual proliferation MISFIT associates with a spindle-associated complex containing the Aurora-related kinase ARK2, EB1, and Myosin-K [PMID:37704606]. Beyond these findings, the biochemical activity of MISFIT and the molecular basis of its paternal effect have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing where and when MISFIT acts was the first step, showing it is a male-gametocyte protein that occupies the nucleus across the transmission stages.","evidence":"Fluorescence microscopy of the tagged protein in male gametocytes, zygotes, and ookinetes","pmids":["19662167"],"confidence":"High","gaps":["No structural or biochemical demonstration of formin/actin-nucleating activity","Nuclear import determinants and binding partners not identified at this stage"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"claim":"Gene disruption defined MISFIT's cellular requirement, revealing that its loss produces ookinetes with reduced genome content and microneme defects yet preserved midgut invasion.","evidence":"Targeted knockout with flow cytometry for DNA content, electron microscopy of micronemes, and invasion assay","pmids":["19662167"],"confidence":"High","gaps":["Mechanism linking MISFIT loss to reduced DNA content unresolved","How microneme defects arise molecularly not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"claim":"The transmission-blocking phenotype was pinpointed to the ookinete-to-oocyst transition, identifying MISFIT as a checkpoint for oocyst maturation.","evidence":"Mosquito infection assay and oocyst phenotypic analysis of the knockout","pmids":["19662167"],"confidence":"High","gaps":["Molecular trigger for the arrest not defined","Whether the sporulation failure is a direct or downstream consequence unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"claim":"Genetic crosses answered whether MISFIT acts from the male or female lineage, demonstrating a strict paternal-allele requirement — a rare gametic-origin effect on downstream development.","evidence":"Epistasis crosses using male-gamete-deficient and female-gamete-deficient parasite lines","pmids":["19662167"],"confidence":"High","gaps":["Molecular basis of the paternal effect (imprinting, protein delivery, timing) not determined","Whether maternal MISFIT protein contributes at all is unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2009,"claim":"Transcriptomics of the knockout began to connect MISFIT to cell-cycle control, showing altered expression of putative cell cycle regulators in mutant ookinetes.","evidence":"Transcriptome analysis of misfit knockout ookinetes","pmids":["19662167"],"confidence":"Medium","gaps":["No direct mechanistic follow-up on the altered transcripts","Cannot distinguish direct regulation from secondary consequences of arrest"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Interactomics placed MISFIT in a molecular context, identifying it as a putative member of a spindle-associated complex during sexual proliferation.","evidence":"Co-immunoprecipitation/mass spectrometry with ARK2 and co-localization by fluorescence microscopy, placing MISFIT with EB1 and Myosin-K","pmids":["37704606"],"confidence":"Medium","gaps":["Interaction not validated by reciprocal pull-down or reconstitution","Functional role of MISFIT within the spindle complex not tested","Direct versus indirect association with ARK2 unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The biochemical activity of MISFIT as a formin-like protein and the molecular mechanism of its paternal effect on the ookinete-to-oocyst transition remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstrated actin-nucleating or other enzymatic activity","Direct substrates or nuclear targets unidentified","Mechanism of paternal-allele-specific requirement uncharacterized"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ARK2/EB1/Myosin-K spindle-associated complex (putative, PF3D7_1403800 as component)"],"partners":["ARK2 (AURORA-RELATED KINASE 2)","EB1","MYOSIN-K"],"other_free_text":["Expressed in male gametocytes; nuclear localization in male gametocytes, zygotes, and ookinetes in P. berghei [#0]","Paternal (male-allele) requirement for the ookinete-to-oocyst transition [#3]","Knockout ookinetes show reduced genome content and microneme defects but retain midgut invasion; arrest before oocyst maturation [#1, #2]","Loss alters transcript levels of putative cell cycle regulators [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19662167","id":"PMC_19662167","title":"Paternal effect of the nuclear formin-like protein MISFIT on Plasmodium development in the mosquito vector.","date":"2009","source":"PLoS 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/40514561","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41748607","id":"","title":"Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41748607","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38563493","id":"","title":"The molecular mechanisms driving Plasmodium cell division.","date":"2024","source":"Biochemical Society 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Section F, Structural biology communications","url":"https://pubmed.ncbi.nlm.nih.gov/25945702","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23434509","id":"","title":"An ancient protein phosphatase, SHLP1, is critical to microneme development in Plasmodium ookinetes and parasite transmission.","date":"2013","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/23434509","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23587146","id":"","title":"A member of the CPW-WPC protein family is expressed in and localized to the surface of developing ookinetes.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/23587146","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23028336","id":"","title":"A unique protein phosphatase with kelch-like domains (PPKL) in Plasmodium modulates ookinete differentiation, motility and invasion.","date":"2012","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/23028336","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20949068","id":"","title":"Concerted action of two formins in gliding motility and host cell invasion by Toxoplasma gondii.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20949068","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"22957089","id":"","title":"A unique Kelch domain phosphatase in Plasmodium regulates ookinete morphology, motility and invasion.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22957089","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MISFIT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":23472,"output_tokens":1485,"usd":0.046345,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6516,"output_tokens":2544,"usd":0.04809,"stage2_stop_reason":"end_turn"},"total_usd":0.094435,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes, and ookinetes, as determined by direct imaging of the tagged protein.\",\n      \"method\": \"Fluorescence microscopy / subcellular localization of tagged protein\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiment in the founding characterization paper, replicated in subsequent studies citing the same finding\",\n      \"pmids\": [\"19662167\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Gene disruption of MISFIT results in mutant ookinetes with reduced genome content (less than wild-type DNA content) and microneme defects, yet these ookinetes still successfully invade the mosquito midgut epithelium.\",\n      \"method\": \"Gene disruption / targeted knockout with flow cytometry (DNA content) and electron microscopy (microneme ultrastructure)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean gene disruption with multiple orthogonal readouts (DNA content, EM ultrastructure, invasion assay) in the founding paper; independently corroborated by multiple subsequent studies\",\n      \"pmids\": [\"19662167\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Disruption of MISFIT causes developmental arrest at the ookinete-to-oocyst transition, blocking malaria transmission; the few oocysts that form are smaller than wild-type and fail to complete sporulation.\",\n      \"method\": \"Gene disruption / targeted knockout with mosquito infection assay and oocyst phenotypic analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic loss-of-function with defined cellular phenotype, independently corroborated by multiple subsequent studies citing the same oocyst arrest phenotype\",\n      \"pmids\": [\"19662167\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Genetic crosses between misfit mutant parasites and lines deficient in either male or female gametes reveal a strict requirement for a male (paternal) misfit allele, demonstrating that MISFIT exerts a paternal effect on development.\",\n      \"method\": \"Genetic cross / epistasis using male-gamete-deficient and female-gamete-deficient parasite lines\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic complementation crosses with defined gamete-deficient lines, a rigorous epistasis approach; finding corroborated by independent studies\",\n      \"pmids\": [\"19662167\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Disruption of MISFIT alters the transcriptional profiles of putative cell cycle regulators in ookinetes, consistent with a role in cell cycle progression.\",\n      \"method\": \"Transcriptome analysis of misfit knockout ookinetes\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — transcriptomic readout in a defined genetic mutant, single lab, no direct mechanistic follow-up of the altered transcripts\",\n      \"pmids\": [\"19662167\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MISFIT is identified as a putative interactor of Aurora-related kinase 2 (ARK2) by interactomic (mass spectrometry) and co-localization studies during sexual proliferation, placing MISFIT in a spindle-associated complex together with EB1 and Myosin-K.\",\n      \"method\": \"Co-immunoprecipitation / mass spectrometry interactomics and co-localization by fluorescence microscopy\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single co-IP/MS experiment from one lab with co-localization support, but MISFIT is listed as a putative interactor and the interaction was not independently validated by reciprocal pull-down or reconstitution\",\n      \"pmids\": [\"37704606\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"MISFIT (PF3D7_1403800) is a nuclear formin-like protein expressed in male gametocytes that localizes to the nuclei of male gametocytes, zygotes, and ookinetes in Plasmodium berghei; its paternal allele is strictly required for the ookinete-to-oocyst developmental transition, as gene disruption produces ookinetes with reduced genome content and microneme defects that can still invade the midgut but then arrest before oocyst maturation, with altered expression of cell cycle regulators; it also associates as a putative component of an ARK2/EB1/Myosin-K spindle complex during sexual development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MISFIT (PF3D7_1403800) is a nuclear formin-like protein that governs the ookinete-to-oocyst developmental transition during the mosquito stage of the Plasmodium life cycle, acting as a determinant of malaria transmission [#2]. In Plasmodium berghei, MISFIT is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes, and ookinetes [#0], and its function is exerted as a strict paternal (male-allele) effect: genetic crosses with gamete-deficient lines demonstrate that a male misfit allele is required for downstream development [#3]. Loss of MISFIT produces ookinetes with reduced genome content and microneme defects that still invade the midgut epithelium but then arrest before oocyst maturation, with the few oocysts that form remaining small and failing to sporulate [#1, #2]; disruption also alters the transcript levels of putative cell cycle regulators, consistent with a role in nuclear/cell-cycle control [#4]. During sexual proliferation MISFIT associates with a spindle-associated complex containing the Aurora-related kinase ARK2, EB1, and Myosin-K [#5]. Beyond these findings, the biochemical activity of MISFIT and the molecular basis of its paternal effect have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing where and when MISFIT acts was the first step, showing it is a male-gametocyte protein that occupies the nucleus across the transmission stages.\",\n      \"evidence\": \"Fluorescence microscopy of the tagged protein in male gametocytes, zygotes, and ookinetes\",\n      \"pmids\": [\"19662167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural or biochemical demonstration of formin/actin-nucleating activity\", \"Nuclear import determinants and binding partners not identified at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Gene disruption defined MISFIT's cellular requirement, revealing that its loss produces ookinetes with reduced genome content and microneme defects yet preserved midgut invasion.\",\n      \"evidence\": \"Targeted knockout with flow cytometry for DNA content, electron microscopy of micronemes, and invasion assay\",\n      \"pmids\": [\"19662167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking MISFIT loss to reduced DNA content unresolved\", \"How microneme defects arise molecularly not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The transmission-blocking phenotype was pinpointed to the ookinete-to-oocyst transition, identifying MISFIT as a checkpoint for oocyst maturation.\",\n      \"evidence\": \"Mosquito infection assay and oocyst phenotypic analysis of the knockout\",\n      \"pmids\": [\"19662167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular trigger for the arrest not defined\", \"Whether the sporulation failure is a direct or downstream consequence unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Genetic crosses answered whether MISFIT acts from the male or female lineage, demonstrating a strict paternal-allele requirement — a rare gametic-origin effect on downstream development.\",\n      \"evidence\": \"Epistasis crosses using male-gamete-deficient and female-gamete-deficient parasite lines\",\n      \"pmids\": [\"19662167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the paternal effect (imprinting, protein delivery, timing) not determined\", \"Whether maternal MISFIT protein contributes at all is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Transcriptomics of the knockout began to connect MISFIT to cell-cycle control, showing altered expression of putative cell cycle regulators in mutant ookinetes.\",\n      \"evidence\": \"Transcriptome analysis of misfit knockout ookinetes\",\n      \"pmids\": [\"19662167\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct mechanistic follow-up on the altered transcripts\", \"Cannot distinguish direct regulation from secondary consequences of arrest\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Interactomics placed MISFIT in a molecular context, identifying it as a putative member of a spindle-associated complex during sexual proliferation.\",\n      \"evidence\": \"Co-immunoprecipitation/mass spectrometry with ARK2 and co-localization by fluorescence microscopy, placing MISFIT with EB1 and Myosin-K\",\n      \"pmids\": [\"37704606\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction not validated by reciprocal pull-down or reconstitution\", \"Functional role of MISFIT within the spindle complex not tested\", \"Direct versus indirect association with ARK2 unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of MISFIT as a formin-like protein and the molecular mechanism of its paternal effect on the ookinete-to-oocyst transition remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstrated actin-nucleating or other enzymatic activity\", \"Direct substrates or nuclear targets unidentified\", \"Mechanism of paternal-allele-specific requirement uncharacterized\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"ARK2/EB1/Myosin-K spindle-associated complex (putative, PF3D7_1403800 as component)\"\n    ],\n    \"partners\": [\n      \"ARK2 (Aurora-related kinase 2)\",\n      \"EB1\",\n      \"Myosin-K\"\n    ],\n    \"other_free_text\": [\n      \"Expressed in male gametocytes; nuclear localization in male gametocytes, zygotes, and ookinetes in P. berghei [#0]\",\n      \"Paternal (male-allele) requirement for the ookinete-to-oocyst transition [#3]\",\n      \"Knockout ookinetes show reduced genome content and microneme defects but retain midgut invasion; arrest before oocyst maturation [#1, #2]\",\n      \"Loss alters transcript levels of putative cell cycle regulators [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1403800","name":null,"product":"nuclear formin-like protein MISFIT, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1038200","name":null,"product":"nuclear formin-like protein MISFIT","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1354300","name":null,"product":"nuclear formin-like protein MISFIT, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MISFIT","evaluation":null}