{"gene":"PF3D7_0314400","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2025,"finding":"PbPP6 (ortholog of PF3D7_0314400) localizes to the plasma membrane of macrogametes and ookinetes in P. berghei, as determined by direct localization experiments.","method":"Direct subcellular localization (fractionation/imaging of parasite stages)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in a single lab study with functional consequence inferred from knockout phenotype, but single method for localization","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Genetic disruption of pbpp6 (∆pbpp6) in P. berghei reduces asexual parasite growth and prolongs survival of infected mice, establishing a role for PPP6 in asexual stage proliferation.","method":"Genetic knockout (∆pbpp6) with in vivo growth and survival readouts","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic disruption with defined phenotypic readout, single lab","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Loss of pbpp6 severely impairs gametogenesis, especially male gametogenesis, substantially reducing ookinete formation and mosquito transmission, establishing PPP6 as required for sexual stage development.","method":"Genetic knockout (∆pbpp6) with gametogenesis, ookinete formation, and mosquito transmission assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with multiple phenotypic readouts (gametogenesis, ookinete, transmission), single lab","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"In ∆pbpp6 parasites, transcriptomic analysis revealed >11-fold downregulation of nek3 (a regulator of MAPK2 in the PKG-Ca²⁺ signaling cascade), accompanied by significantly diminished intracellular cGMP levels, decreased cytosolic Ca²⁺ mobilization, and reduced DNA replication in activated gametocytes, placing PPP6 upstream of the cGMP-PKG-Ca²⁺ signaling pathway during gametogenesis.","method":"Transcriptomic analysis and functional assays (cGMP measurement, Ca²⁺ mobilization, DNA replication) in ∆pbpp6 parasites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (transcriptomics, cGMP assay, Ca²⁺ imaging, DNA replication) in single lab placing PPP6 in pathway","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Phosphoproteomic analysis in ∆pbpp6 parasites detected increased phosphorylation at Ser508 of guanylyl cyclase alpha (GCα), indicating that PbPP6 dephosphorylates GCα at this site to modulate cGMP-PKG-Ca²⁺ signaling during gametogenesis.","method":"Phosphoproteomic analysis (mass spectrometry) comparing ∆pbpp6 and wild-type parasites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — phosphoproteomics identifies a specific substrate site, single lab, no in vitro dephosphorylation reconstitution to confirm direct substrate relationship","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Loss of pbpp6 alters expression of messenger ribonucleoproteins (mRNPs) in female gametocytes, suggesting PPP6 affects translational repression of stored mRNAs and post-fertilization development in mosquitoes.","method":"Transcriptomic/proteomic analysis in ∆pbpp6 female gametocytes","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect evidence (altered mRNP expression) without direct reconstitution of the translational repression mechanism","pmids":["40623036"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2008,"finding":"Bioinformatic analysis classified PF3D7_0314400 as a putative serine/threonine protein phosphatase belonging to the PP family within the P. falciparum phosphatome; no human homologue cluster was identified for some P. falciparum phosphatases, suggesting potential for selective drug targeting.","method":"Bioinformatics (genome database mining, phylogenetic analysis)","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation of PPP6 specifically","pmids":["18793411"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PbPP6 (the P. berghei ortholog of PF3D7_0314400) is a plasma membrane-associated serine/threonine phosphatase in macrogametes and ookinetes that is required for asexual growth, male gametogenesis, ookinete formation, and mosquito transmission; mechanistically, it acts upstream of the cGMP-PKG-Ca²⁺ signaling pathway by dephosphorylating guanylyl cyclase alpha at Ser508 to promote cGMP production and downstream Ca²⁺ mobilization during gametogenesis."},"narrative":{"mechanistic_narrative":"PF3D7_0314400 (PPP6) is a serine/threonine protein phosphatase that regulates both asexual proliferation and sexual-stage development in Plasmodium, characterized principally through its P. berghei ortholog PbPP6 [PMID:40623036]. PbPP6 localizes to the plasma membrane of macrogametes and ookinetes, and its genetic disruption reduces asexual parasite growth while severely impairing gametogenesis—particularly male gametogenesis—thereby diminishing ookinete formation and mosquito transmission [PMID:40623036]. Mechanistically, PbPP6 acts upstream of the cGMP-PKG-Ca²⁺ signaling cascade during gametogenesis: loss of pbpp6 lowers intracellular cGMP, reduces cytosolic Ca²⁺ mobilization and DNA replication in activated gametocytes, and increases phosphorylation of guanylyl cyclase alpha at Ser508, identifying GCα as a substrate site dephosphorylated by PbPP6 to promote cGMP production [PMID:40623036]. Bioinformatic classification originally placed PF3D7_0314400 in the PP phosphatase family of the P. falciparum phosphatome [PMID:18793411]. Beyond the P. berghei ortholog phenotypes and the GCα Ser508 substrate link, no direct biochemical reconstitution of PPP6 catalytic activity has been characterized in the available corpus.","teleology":[{"year":2008,"claim":"Before any functional work, it was unknown what class of enzyme PF3D7_0314400 encoded; genome-wide phosphatome analysis classified it as a putative serine/threonine phosphatase of the PP family, framing it as a candidate regulator and possible selective drug target.","evidence":"Bioinformatic genome mining and phylogenetic analysis of the P. falciparum phosphatome","pmids":["18793411"],"confidence":"Low","gaps":["Purely computational prediction with no experimental validation of PPP6 activity","No substrate, localization, or phenotype established for the gene at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The cellular role of the enzyme was unknown; localization and genetic disruption of the P. berghei ortholog established PbPP6 as a plasma-membrane phosphatase required for asexual growth and for sexual-stage development and transmission.","evidence":"Subcellular localization plus ∆pbpp6 knockout with in vivo growth, gametogenesis, ookinete, and mosquito transmission assays in P. berghei","pmids":["40623036"],"confidence":"Medium","gaps":["Localization rests on a single method","Whether the P. falciparum ortholog shows the same phenotype is not tested","Molecular basis of plasma-membrane targeting unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"How PbPP6 loss disrupts gametogenesis was unknown; combined transcriptomic and functional assays placed PbPP6 upstream of the cGMP-PKG-Ca²⁺ cascade by showing reduced cGMP, impaired Ca²⁺ mobilization, downregulated nek3, and reduced DNA replication in its absence.","evidence":"Transcriptomics plus cGMP measurement, Ca²⁺ imaging, and DNA replication assays in ∆pbpp6 P. berghei parasites","pmids":["40623036"],"confidence":"Medium","gaps":["Placement in the pathway is inferential from correlated defects","Direct catalytic control of individual pathway nodes not demonstrated in vitro"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"The molecular substrate connecting PbPP6 to cGMP signaling was unknown; phosphoproteomics identified guanylyl cyclase alpha Ser508 as a site hyperphosphorylated in the knockout, implicating GCα as the dephosphorylation target modulating cGMP output.","evidence":"Mass-spectrometry phosphoproteomics comparing ∆pbpp6 and wild-type P. berghei parasites","pmids":["40623036"],"confidence":"Medium","gaps":["No in vitro dephosphorylation reconstitution confirming a direct enzyme-substrate relationship","Ser508 hyperphosphorylation could be an indirect consequence of altered signaling"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Whether PbPP6 influences post-fertilization development was unknown; altered mRNP expression in ∆pbpp6 female gametocytes suggested a role in translational repression of stored mRNAs.","evidence":"Transcriptomic/proteomic profiling of ∆pbpp6 female gametocytes in P. berghei","pmids":["40623036"],"confidence":"Low","gaps":["Indirect evidence; the translational repression mechanism was not directly reconstituted","Link between phosphatase activity and mRNP regulation unestablished"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether the P. falciparum enzyme PF3D7_0314400 itself replicates the biochemical, localization, and phenotypic properties inferred from its P. berghei ortholog, and whether GCα Ser508 is a direct catalytic substrate, remain open.","evidence":"No direct P. falciparum functional or in vitro biochemical study of PF3D7_0314400 in the corpus","pmids":[],"confidence":"Low","gaps":["No P. falciparum knockout or localization data for PF3D7_0314400","No reconstituted phosphatase assay with defined substrates","Structural basis and regulatory subunit context uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["GUANYLYL CYCLASE ALPHA (GCΑ), SER508 SUBSTRATE SITE — P. BERGHEI [#4]"],"other_free_text":["Characterized principally via the P. berghei ortholog PbPP6; direct experimental data on the P. falciparum gene PF3D7_0314400 itself is limited to bioinformatic phosphatome classification [#6].","Acts upstream of the cGMP-PKG-Ca²⁺ signaling cascade during gametogenesis in P. berghei [#3].","Loss alters mRNP expression in female gametocytes, implicating a role in translational control (Low confidence) [#5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18793411","id":"PMC_18793411","title":"The protein-phosphatome of the human malaria parasite Plasmodium falciparum.","date":"2008","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18793411","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10340482","id":"PMC_10340482","title":"Characterization of protein Ser/Thr phosphatases of the malaria parasite, Plasmodium falciparum: inhibition of the parasitic calcineurin by cyclophilin-cyclosporin complex.","date":"1999","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10340482","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40623036","id":"PMC_40623036","title":"Loss of serine/threonine protein phosphatase 6 severely impairs sexual stage development in malaria parasite Plasmodium berghei.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/40623036","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["serine/threonine protein phosphatase 6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4398,"output_tokens":1792,"usd":0.020037,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6990,"output_tokens":2733,"usd":0.051638,"stage2_stop_reason":"end_turn"},"total_usd":0.071675,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"PbPP6 (ortholog of PF3D7_0314400) localizes to the plasma membrane of macrogametes and ookinetes in P. berghei, as determined by direct localization experiments.\",\n      \"method\": \"Direct subcellular localization (fractionation/imaging of parasite stages)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in a single lab study with functional consequence inferred from knockout phenotype, but single method for localization\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Genetic disruption of pbpp6 (∆pbpp6) in P. berghei reduces asexual parasite growth and prolongs survival of infected mice, establishing a role for PPP6 in asexual stage proliferation.\",\n      \"method\": \"Genetic knockout (∆pbpp6) with in vivo growth and survival readouts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic disruption with defined phenotypic readout, single lab\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of pbpp6 severely impairs gametogenesis, especially male gametogenesis, substantially reducing ookinete formation and mosquito transmission, establishing PPP6 as required for sexual stage development.\",\n      \"method\": \"Genetic knockout (∆pbpp6) with gametogenesis, ookinete formation, and mosquito transmission assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with multiple phenotypic readouts (gametogenesis, ookinete, transmission), single lab\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In ∆pbpp6 parasites, transcriptomic analysis revealed >11-fold downregulation of nek3 (a regulator of MAPK2 in the PKG-Ca²⁺ signaling cascade), accompanied by significantly diminished intracellular cGMP levels, decreased cytosolic Ca²⁺ mobilization, and reduced DNA replication in activated gametocytes, placing PPP6 upstream of the cGMP-PKG-Ca²⁺ signaling pathway during gametogenesis.\",\n      \"method\": \"Transcriptomic analysis and functional assays (cGMP measurement, Ca²⁺ mobilization, DNA replication) in ∆pbpp6 parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (transcriptomics, cGMP assay, Ca²⁺ imaging, DNA replication) in single lab placing PPP6 in pathway\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Phosphoproteomic analysis in ∆pbpp6 parasites detected increased phosphorylation at Ser508 of guanylyl cyclase alpha (GCα), indicating that PbPP6 dephosphorylates GCα at this site to modulate cGMP-PKG-Ca²⁺ signaling during gametogenesis.\",\n      \"method\": \"Phosphoproteomic analysis (mass spectrometry) comparing ∆pbpp6 and wild-type parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — phosphoproteomics identifies a specific substrate site, single lab, no in vitro dephosphorylation reconstitution to confirm direct substrate relationship\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of pbpp6 alters expression of messenger ribonucleoproteins (mRNPs) in female gametocytes, suggesting PPP6 affects translational repression of stored mRNAs and post-fertilization development in mosquitoes.\",\n      \"method\": \"Transcriptomic/proteomic analysis in ∆pbpp6 female gametocytes\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect evidence (altered mRNP expression) without direct reconstitution of the translational repression mechanism\",\n      \"pmids\": [\"40623036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Bioinformatic analysis classified PF3D7_0314400 as a putative serine/threonine protein phosphatase belonging to the PP family within the P. falciparum phosphatome; no human homologue cluster was identified for some P. falciparum phosphatases, suggesting potential for selective drug targeting.\",\n      \"method\": \"Bioinformatics (genome database mining, phylogenetic analysis)\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation of PPP6 specifically\",\n      \"pmids\": [\"18793411\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PbPP6 (the P. berghei ortholog of PF3D7_0314400) is a plasma membrane-associated serine/threonine phosphatase in macrogametes and ookinetes that is required for asexual growth, male gametogenesis, ookinete formation, and mosquito transmission; mechanistically, it acts upstream of the cGMP-PKG-Ca²⁺ signaling pathway by dephosphorylating guanylyl cyclase alpha at Ser508 to promote cGMP production and downstream Ca²⁺ mobilization during gametogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0314400 (PPP6) is a serine/threonine protein phosphatase that regulates both asexual proliferation and sexual-stage development in Plasmodium, characterized principally through its P. berghei ortholog PbPP6 [#1, #2]. PbPP6 localizes to the plasma membrane of macrogametes and ookinetes, and its genetic disruption reduces asexual parasite growth while severely impairing gametogenesis—particularly male gametogenesis—thereby diminishing ookinete formation and mosquito transmission [#0, #1, #2]. Mechanistically, PbPP6 acts upstream of the cGMP-PKG-Ca²⁺ signaling cascade during gametogenesis: loss of pbpp6 lowers intracellular cGMP, reduces cytosolic Ca²⁺ mobilization and DNA replication in activated gametocytes, and increases phosphorylation of guanylyl cyclase alpha at Ser508, identifying GCα as a substrate site dephosphorylated by PbPP6 to promote cGMP production [#3, #4]. Bioinformatic classification originally placed PF3D7_0314400 in the PP phosphatase family of the P. falciparum phosphatome [#6]. Beyond the P. berghei ortholog phenotypes and the GCα Ser508 substrate link, no direct biochemical reconstitution of PPP6 catalytic activity has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Before any functional work, it was unknown what class of enzyme PF3D7_0314400 encoded; genome-wide phosphatome analysis classified it as a putative serine/threonine phosphatase of the PP family, framing it as a candidate regulator and possible selective drug target.\",\n      \"evidence\": \"Bioinformatic genome mining and phylogenetic analysis of the P. falciparum phosphatome\",\n      \"pmids\": [\"18793411\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational prediction with no experimental validation of PPP6 activity\",\n        \"No substrate, localization, or phenotype established for the gene at this stage\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The cellular role of the enzyme was unknown; localization and genetic disruption of the P. berghei ortholog established PbPP6 as a plasma-membrane phosphatase required for asexual growth and for sexual-stage development and transmission.\",\n      \"evidence\": \"Subcellular localization plus ∆pbpp6 knockout with in vivo growth, gametogenesis, ookinete, and mosquito transmission assays in P. berghei\",\n      \"pmids\": [\"40623036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization rests on a single method\",\n        \"Whether the P. falciparum ortholog shows the same phenotype is not tested\",\n        \"Molecular basis of plasma-membrane targeting unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How PbPP6 loss disrupts gametogenesis was unknown; combined transcriptomic and functional assays placed PbPP6 upstream of the cGMP-PKG-Ca²⁺ cascade by showing reduced cGMP, impaired Ca²⁺ mobilization, downregulated nek3, and reduced DNA replication in its absence.\",\n      \"evidence\": \"Transcriptomics plus cGMP measurement, Ca²⁺ imaging, and DNA replication assays in ∆pbpp6 P. berghei parasites\",\n      \"pmids\": [\"40623036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Placement in the pathway is inferential from correlated defects\",\n        \"Direct catalytic control of individual pathway nodes not demonstrated in vitro\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The molecular substrate connecting PbPP6 to cGMP signaling was unknown; phosphoproteomics identified guanylyl cyclase alpha Ser508 as a site hyperphosphorylated in the knockout, implicating GCα as the dephosphorylation target modulating cGMP output.\",\n      \"evidence\": \"Mass-spectrometry phosphoproteomics comparing ∆pbpp6 and wild-type P. berghei parasites\",\n      \"pmids\": [\"40623036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro dephosphorylation reconstitution confirming a direct enzyme-substrate relationship\",\n        \"Ser508 hyperphosphorylation could be an indirect consequence of altered signaling\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether PbPP6 influences post-fertilization development was unknown; altered mRNP expression in ∆pbpp6 female gametocytes suggested a role in translational repression of stored mRNAs.\",\n      \"evidence\": \"Transcriptomic/proteomic profiling of ∆pbpp6 female gametocytes in P. berghei\",\n      \"pmids\": [\"40623036\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Indirect evidence; the translational repression mechanism was not directly reconstituted\",\n        \"Link between phosphatase activity and mRNP regulation unestablished\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the P. falciparum enzyme PF3D7_0314400 itself replicates the biochemical, localization, and phenotypic properties inferred from its P. berghei ortholog, and whether GCα Ser508 is a direct catalytic substrate, remain open.\",\n      \"evidence\": \"No direct P. falciparum functional or in vitro biochemical study of PF3D7_0314400 in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No P. falciparum knockout or localization data for PF3D7_0314400\",\n        \"No reconstituted phosphatase assay with defined substrates\",\n        \"Structural basis and regulatory subunit context uncharacterized\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004722\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007165\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Guanylyl cyclase alpha (GCα), Ser508 substrate site — P. berghei [#4]\"\n    ],\n    \"other_free_text\": [\n      \"Characterized principally via the P. berghei ortholog PbPP6; direct experimental data on the P. falciparum gene PF3D7_0314400 itself is limited to bioinformatic phosphatome classification [#6].\",\n      \"Acts upstream of the cGMP-PKG-Ca²⁺ signaling cascade during gametogenesis in P. berghei [#3].\",\n      \"Loss alters mRNP expression in female gametocytes, implicating a role in translational control (Low confidence) [#5].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0314400","name":null,"product":"serine/threonine protein phosphatase 6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0412100","name":null,"product":"serine/threonine protein phosphatase 6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0827700","name":null,"product":"serine/threonine protein phosphatase 6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PPP6","evaluation":null}