{"gene":"PF3D7_1430100","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2014,"finding":"PF3D7_1430100 (PTPA) binds directly to PfPP2A and activates its phosphatase activity in vitro; three specific residues—V283, G292, and M296—are indispensable for the interaction, and G292 is essential for activation.","method":"In vitro binding assay, functional phosphatase activation assay, and site-directed mutagenesis of specific residues","journal":"International journal of molecular sciences","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of binding and activation combined with active-site mutagenesis identifying three specific residues, all in a single focused study","pmids":["24521882"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PF3D7_1430100 (PTPA) and PfPP2A co-localize to the same subcellular compartment in blood-stage parasites, consistent with a physical interaction in vivo.","method":"Localization studies (immunofluorescence/co-localization) in blood-stage parasites","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, co-localization only with no functional consequence directly demonstrated for localization itself","pmids":["24521882"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PF3D7_1430100 (PTPA) blocked the G2/M transition when expressed in Xenopus oocytes, placing it as a regulator of cell-cycle progression through its PP2A regulatory activity.","method":"Xenopus oocyte G2/M transition assay (functional cell-cycle block assay)","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean cell-cycle phenotype in a defined heterologous assay, single lab, single method","pmids":["24521882"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Genetic studies in P. falciparum suggested that PF3D7_1430100 (PTPA) is essential for completion of the intraerythrocytic lifecycle.","method":"Genetic essentiality analysis (attempted gene disruption/knockdown in P. falciparum)","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, genetic essentiality inferred from inability to disrupt, no conditional KO or complementation described in abstract","pmids":["24521882"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The genomic locus of PF3D7_1430100 (PTPA) is located at the boundary of two large superdomains that form on chromosome 14 specifically in gametocytes, and gametocytes express a distinct variant of the transcript lacking exon 1 and show higher expression of PF3D7_1430100 compared to intraerythrocytic development cycle stages.","method":"Hi-C genome organization mapping, RNA-seq/transcript variant analysis, PCR and Southern blot confirmation of the genomic boundary","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Hi-C with multiple orthogonal validation methods (PCR, Southern blot), single study but robust genome-wide methodology with specific locus follow-up","pmids":["29765020"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]}],"current_model":"PF3D7_1430100 (PTPA) is a PhosphoTyrosyl Phosphatase Activator that directly binds to and activates PfPP2A through residues V283, G292, and M296, co-localizes with PfPP2A in blood-stage parasites, is genetically essential for intraerythrocytic development, and regulates cell-cycle progression at the G2/M transition; its genomic locus additionally sits at a gametocyte-specific chromosome 14 superdomain boundary where a distinct transcript isoform lacking exon 1 is expressed at elevated levels."},"narrative":{"mechanistic_narrative":"PF3D7_1430100 (PTPA) is a phosphotyrosyl phosphatase activator that functions as a direct activator of PfPP2A in Plasmodium falciparum and thereby couples protein phosphatase regulation to cell-cycle control [PMID:24521882]. It binds PfPP2A directly and stimulates its phosphatase activity in vitro, with residues V283, G292, and M296 indispensable for the interaction and G292 specifically required for activation [PMID:24521882]; consistent with a physiological interaction, the two proteins co-localize in blood-stage parasites [PMID:24521882]. Functionally, heterologous expression in Xenopus oocytes blocks the G2/M transition, placing PTPA-mediated PP2A regulation at cell-cycle progression [PMID:24521882], and its gene is essential for completion of the intraerythrocytic lifecycle [PMID:24521882]. Independently of its enzymatic role, the PTPA genomic locus sits at the boundary of two gametocyte-specific chromosome 14 superdomains, and gametocytes express a distinct transcript isoform lacking exon 1 at elevated levels relative to asexual stages [PMID:29765020]. Beyond these findings, the mechanism of PTPA has not been further characterized in the available corpus.","teleology":[{"year":2014,"claim":"Whether PF3D7_1430100 acts biochemically on PfPP2A was unknown; direct reconstitution established it as a genuine activator and mapped the residues required for binding versus activation.","evidence":"in vitro binding and phosphatase activation assays with site-directed mutagenesis of V283, G292, M296 in P. falciparum PTPA","pmids":["24521882"],"confidence":"High","gaps":["No structural model of the PTPA-PfPP2A complex","Mechanism by which G292 drives activation versus binding not resolved","Full substrate spectrum of the activated phosphatase not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"To test whether the in vitro interaction reflects an in vivo association, co-localization was assessed in blood-stage parasites, supporting a physical partnership.","evidence":"immunofluorescence/co-localization in blood-stage P. falciparum","pmids":["24521882"],"confidence":"Medium","gaps":["Co-localization does not prove direct in-cell binding","Subcellular compartment not molecularly defined","No functional consequence of localization demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The cellular process governed by PTPA was unknown; a heterologous G2/M assay linked its PP2A-regulatory activity to cell-cycle progression.","evidence":"Xenopus oocyte G2/M transition block assay","pmids":["24521882"],"confidence":"Medium","gaps":["Phenotype shown only in heterologous oocytes, not in parasite cell cycle","Downstream PP2A substrates driving the block not identified","Relevance to native parasite G2/M not tested directly"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Whether the gene is dispensable was tested to gauge its importance for the parasite; disruption attempts indicated essentiality for the intraerythrocytic cycle.","evidence":"attempted gene disruption/knockdown in P. falciparum","pmids":["24521882"],"confidence":"Low","gaps":["Essentiality inferred from failure to disrupt without conditional knockout or complementation","Stage-specific requirement not resolved","No rescue experiment reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Genome-organization mapping revealed a stage-specific regulatory feature at the locus, showing the PTPA gene sits at a gametocyte-specific chromatin boundary with an alternative, upregulated transcript.","evidence":"Hi-C genome organization mapping with RNA-seq transcript-variant analysis, PCR and Southern blot validation in P. falciparum NF54","pmids":["29765020"],"confidence":"Medium","gaps":["Function of the exon-1-lacking gametocyte isoform unknown","Whether the isoform encodes active or altered protein untested","Link between superdomain boundary and PTPA expression is correlative"],"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":null,"claim":"It remains unknown whether the gametocyte-specific exon-1-lacking isoform produces a functional protein and how PTPA-PfPP2A signaling is deployed differently across asexual and sexual stages.","evidence":"","pmids":[],"confidence":"Low","gaps":["No characterization of the gametocyte isoform's activity toward PfPP2A","No in-parasite mechanistic link between PTPA activation and G2/M control","No structural or full substrate-level understanding of the PTPA-PfPP2A axis"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPP2A"],"other_free_text":["Direct binding to and activation of PfPP2A requires residues V283, G292, and M296; G292 is specifically essential for activation [#0]","Co-localizes with PfPP2A in blood-stage parasites [#1]","Genetically essential for completion of the intraerythrocytic lifecycle [#3]","Genomic locus sits at a gametocyte-specific chromosome 14 superdomain boundary; gametocytes express an elevated transcript isoform lacking exon 1 [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24521882","id":"PMC_24521882","title":"PhosphoTyrosyl phosphatase activator of Plasmodium falciparum: identification of its residues involved in binding to and activation of PP2A.","date":"2014","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/24521882","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39391471","id":"","title":"Comparative genomics of two protozoans Dictyostelium discoideum and Plasmodium falciparum reveals conserved as well as distinct regulatory pathways crucial for exploring novel therapeutic targets for Malaria.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/39391471","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTPA"],"competing_organism_flag":true,"competing_organism_match":"Dictyostelium","competing_organism_only":false},{"pmid":"29765020","id":"","title":"Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29765020","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTPA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39204244","id":"","title":"Insights into Peptidyl-Prolyl cis-trans Isomerases from Clinically Important Protozoans: From Structure to Potential Biotechnological Applications.","date":"2024","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/39204244","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTPA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33425787","id":"","title":"From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium.","date":"2020","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33425787","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTPA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6868,"output_tokens":1289,"usd":0.01997,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6178,"output_tokens":2376,"usd":0.045145,"stage2_stop_reason":"end_turn"},"total_usd":0.065115,"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\": 2014,\n      \"finding\": \"PF3D7_1430100 (PTPA) binds directly to PfPP2A and activates its phosphatase activity in vitro; three specific residues—V283, G292, and M296—are indispensable for the interaction, and G292 is essential for activation.\",\n      \"method\": \"In vitro binding assay, functional phosphatase activation assay, and site-directed mutagenesis of specific residues\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of binding and activation combined with active-site mutagenesis identifying three specific residues, all in a single focused study\",\n      \"pmids\": [\"24521882\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PF3D7_1430100 (PTPA) and PfPP2A co-localize to the same subcellular compartment in blood-stage parasites, consistent with a physical interaction in vivo.\",\n      \"method\": \"Localization studies (immunofluorescence/co-localization) in blood-stage parasites\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, co-localization only with no functional consequence directly demonstrated for localization itself\",\n      \"pmids\": [\"24521882\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PF3D7_1430100 (PTPA) blocked the G2/M transition when expressed in Xenopus oocytes, placing it as a regulator of cell-cycle progression through its PP2A regulatory activity.\",\n      \"method\": \"Xenopus oocyte G2/M transition assay (functional cell-cycle block assay)\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean cell-cycle phenotype in a defined heterologous assay, single lab, single method\",\n      \"pmids\": [\"24521882\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Genetic studies in P. falciparum suggested that PF3D7_1430100 (PTPA) is essential for completion of the intraerythrocytic lifecycle.\",\n      \"method\": \"Genetic essentiality analysis (attempted gene disruption/knockdown in P. falciparum)\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, genetic essentiality inferred from inability to disrupt, no conditional KO or complementation described in abstract\",\n      \"pmids\": [\"24521882\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The genomic locus of PF3D7_1430100 (PTPA) is located at the boundary of two large superdomains that form on chromosome 14 specifically in gametocytes, and gametocytes express a distinct variant of the transcript lacking exon 1 and show higher expression of PF3D7_1430100 compared to intraerythrocytic development cycle stages.\",\n      \"method\": \"Hi-C genome organization mapping, RNA-seq/transcript variant analysis, PCR and Southern blot confirmation of the genomic boundary\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Hi-C with multiple orthogonal validation methods (PCR, Southern blot), single study but robust genome-wide methodology with specific locus follow-up\",\n      \"pmids\": [\"29765020\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1430100 (PTPA) is a PhosphoTyrosyl Phosphatase Activator that directly binds to and activates PfPP2A through residues V283, G292, and M296, co-localizes with PfPP2A in blood-stage parasites, is genetically essential for intraerythrocytic development, and regulates cell-cycle progression at the G2/M transition; its genomic locus additionally sits at a gametocyte-specific chromosome 14 superdomain boundary where a distinct transcript isoform lacking exon 1 is expressed at elevated levels.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1430100 (PTPA) is a phosphotyrosyl phosphatase activator that functions as a direct activator of PfPP2A in Plasmodium falciparum and thereby couples protein phosphatase regulation to cell-cycle control [#0, #2]. It binds PfPP2A directly and stimulates its phosphatase activity in vitro, with residues V283, G292, and M296 indispensable for the interaction and G292 specifically required for activation [#0]; consistent with a physiological interaction, the two proteins co-localize in blood-stage parasites [#1]. Functionally, heterologous expression in Xenopus oocytes blocks the G2/M transition, placing PTPA-mediated PP2A regulation at cell-cycle progression [#2], and its gene is essential for completion of the intraerythrocytic lifecycle [#3]. Independently of its enzymatic role, the PTPA genomic locus sits at the boundary of two gametocyte-specific chromosome 14 superdomains, and gametocytes express a distinct transcript isoform lacking exon 1 at elevated levels relative to asexual stages [#4]. Beyond these findings, the mechanism of PTPA has not been further characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether PF3D7_1430100 acts biochemically on PfPP2A was unknown; direct reconstitution established it as a genuine activator and mapped the residues required for binding versus activation.\",\n      \"evidence\": \"in vitro binding and phosphatase activation assays with site-directed mutagenesis of V283, G292, M296 in P. falciparum PTPA\",\n      \"pmids\": [\"24521882\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the PTPA-PfPP2A complex\", \"Mechanism by which G292 drives activation versus binding not resolved\", \"Full substrate spectrum of the activated phosphatase not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To test whether the in vitro interaction reflects an in vivo association, co-localization was assessed in blood-stage parasites, supporting a physical partnership.\",\n      \"evidence\": \"immunofluorescence/co-localization in blood-stage P. falciparum\",\n      \"pmids\": [\"24521882\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-localization does not prove direct in-cell binding\", \"Subcellular compartment not molecularly defined\", \"No functional consequence of localization demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The cellular process governed by PTPA was unknown; a heterologous G2/M assay linked its PP2A-regulatory activity to cell-cycle progression.\",\n      \"evidence\": \"Xenopus oocyte G2/M transition block assay\",\n      \"pmids\": [\"24521882\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phenotype shown only in heterologous oocytes, not in parasite cell cycle\", \"Downstream PP2A substrates driving the block not identified\", \"Relevance to native parasite G2/M not tested directly\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether the gene is dispensable was tested to gauge its importance for the parasite; disruption attempts indicated essentiality for the intraerythrocytic cycle.\",\n      \"evidence\": \"attempted gene disruption/knockdown in P. falciparum\",\n      \"pmids\": [\"24521882\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Essentiality inferred from failure to disrupt without conditional knockout or complementation\", \"Stage-specific requirement not resolved\", \"No rescue experiment reported\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Genome-organization mapping revealed a stage-specific regulatory feature at the locus, showing the PTPA gene sits at a gametocyte-specific chromatin boundary with an alternative, upregulated transcript.\",\n      \"evidence\": \"Hi-C genome organization mapping with RNA-seq transcript-variant analysis, PCR and Southern blot validation in P. falciparum NF54\",\n      \"pmids\": [\"29765020\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Function of the exon-1-lacking gametocyte isoform unknown\", \"Whether the isoform encodes active or altered protein untested\", \"Link between superdomain boundary and PTPA expression is correlative\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether the gametocyte-specific exon-1-lacking isoform produces a functional protein and how PTPA-PfPP2A signaling is deployed differently across asexual and sexual stages.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No characterization of the gametocyte isoform's activity toward PfPP2A\", \"No in-parasite mechanistic link between PTPA activation and G2/M control\", \"No structural or full substrate-level understanding of the PTPA-PfPP2A axis\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008601\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000086\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0007346\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfPP2A\"],\n    \"other_free_text\": [\n      \"Direct binding to and activation of PfPP2A requires residues V283, G292, and M296; G292 is specifically essential for activation [#0]\",\n      \"Co-localizes with PfPP2A in blood-stage parasites [#1]\",\n      \"Genetically essential for completion of the intraerythrocytic lifecycle [#3]\",\n      \"Genomic locus sits at a gametocyte-specific chromosome 14 superdomain boundary; gametocytes express an elevated transcript isoform lacking exon 1 [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1430100","name":null,"product":"serine/threonine protein phosphatase 2A activator","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1014600","name":null,"product":"serine/threonine protein phosphatase 2A activator, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1328600","name":null,"product":"serine/threonine protein phosphatase 2A activator, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PTPA","evaluation":null}