{"gene":"PF3D7_0930800","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_0930800 (PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and forms a complex with PfPP1 in the parasite, acting as a major regulatory partner of PfPP1.","method":"In vitro direct interaction assay and co-immunoprecipitation/complex detection in parasite lysate","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro interaction plus co-complex detection in parasite, two orthogonal methods in a single lab","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"In the Xenopus oocyte model, PfRCC-PIP (PF3D7_0930800) interacts with endogenous PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1 activity.","method":"Xenopus oocyte functional assay with progesterone-induced maturation","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional oocyte assay with progesterone dose-response, single lab, single model system","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The RCC1 motif-containing region of PfRCC-PIP (PF3D7_0930800) interacts with the parasite kinase CDPK7, identifying the protein as a kinase anchoring protein in addition to its role as a phosphatase anchor.","method":"Protein interaction assay (region-specific binding to CDPK7)","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single interaction assay with no mutagenesis validation or functional consequence defined","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies failed to produce viable knock-out parasites for PfRCC-PIP (PF3D7_0930800), suggesting the gene is essential for P. falciparum survival.","method":"Reverse genetics / attempted gene knockout","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic essentiality inferred from inability to obtain viable KO parasites, single lab but standard approach","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0930800 (PfRCC-PIP) is an essential P. falciparum protein that functions as a dual kinase- and phosphatase-anchoring scaffold: it directly binds and activates PfPP1 (Protein Phosphatase type-1) and also associates with the kinase CDPK7 via its RCC1 motif-containing region, thereby providing a platform that coordinates phosphorylation/dephosphorylation processes in the parasite."},"narrative":{"mechanistic_narrative":"PF3D7_0930800 (PfRCC-PIP) is an essential Plasmodium falciparum protein that functions as a scaffold coordinating phosphorylation and dephosphorylation, established through direct interaction and functional assays [PMID:30429842]. It directly binds P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and forms a complex with PfPP1 in parasite lysate, acting as a major regulatory partner of the phosphatase [PMID:30429842]; in a heterologous Xenopus oocyte system, PfRCC-PIP interacts with endogenous PP1 and synergizes with suboptimal progesterone to drive oocyte maturation, indicating that it activates PP1 activity [PMID:30429842]. Its RCC1 motif-containing region additionally binds the parasite kinase CDPK7, marking the protein as a kinase-anchoring platform as well as a phosphatase anchor [PMID:30429842]. Attempted knockout failed to yield viable parasites, indicating the gene is essential for P. falciparum survival [PMID:30429842]. Beyond these interaction and essentiality findings, no further mechanistic detail — including substrate specificity, structural basis of binding, or the functional consequence of the CDPK7 association — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"It was unknown which regulatory proteins govern PfPP1 in P. falciparum; identifying a direct PfPP1-binding partner established PF3D7_0930800 as a phosphatase-anchoring regulator.","evidence":"In vitro direct interaction assay plus co-immunoprecipitation/complex detection in parasite lysate","pmids":["30429842"],"confidence":"Medium","gaps":["The PfPP1-binding motif/interface on PF3D7_0930800 was not mapped by mutagenesis","Substrates dephosphorylated by the PfPP1 complex were not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether the interaction was merely physical or functionally regulatory was open; a heterologous oocyte assay showed PfRCC-PIP activates PP1 activity.","evidence":"Xenopus oocyte maturation assay with progesterone dose-response and endogenous PP1","pmids":["30429842"],"confidence":"Medium","gaps":["The activating effect was shown on endogenous Xenopus PP1, not directly quantified on PfPP1 in the parasite","Physiological process in the parasite regulated by this activation is undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"It was unclear whether the protein engaged only phosphatases; binding of its RCC1 motif region to CDPK7 established it as a dual kinase/phosphatase anchor.","evidence":"Region-specific protein interaction assay with CDPK7","pmids":["30429842"],"confidence":"Low","gaps":["Single interaction assay without mutagenesis validation or defined functional consequence","No reciprocal or in-parasite confirmation of the CDPK7 association","Whether kinase and phosphatase binding are simultaneous or mutually exclusive is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The biological importance of the gene was unknown; failure to obtain viable knockouts indicated essentiality for blood-stage survival.","evidence":"Reverse genetics / attempted gene knockout","pmids":["30429842"],"confidence":"Medium","gaps":["Essentiality inferred from KO failure, not confirmed by conditional knockdown/knockout","The essential stage and process were not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PF3D7_0930800 integrates PfPP1 and CDPK7 activities on shared substrates, and which cellular process depends on this scaffold, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrates of the coordinated kinase/phosphatase platform identified","No structural model of the scaffold or its binding interfaces","Subcellular localization and stage-specific role uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfRCC-PIP–PfPP1 complex"],"partners":["PFPP1 (P. FALCIPARUM PROTEIN PHOSPHATASE TYPE-1)","CDPK7"],"other_free_text":["Essential for P. falciparum survival (knockout not viable)","Contains an RCC1 motif-containing region that mediates CDPK7 binding","Activates PP1 activity in a heterologous Xenopus oocyte maturation assay"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30429842","id":"PMC_30429842","title":"Characterization of a Protein Phosphatase Type-1 and a Kinase Anchoring Protein in Plasmodium falciparum.","date":"2018","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30429842","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["regulator of chromosome condensation"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3245,"output_tokens":1015,"usd":0.01248,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5716,"output_tokens":2068,"usd":0.04014,"stage2_stop_reason":"end_turn"},"total_usd":0.05262,"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\": 2018,\n      \"finding\": \"PF3D7_0930800 (PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and forms a complex with PfPP1 in the parasite, acting as a major regulatory partner of PfPP1.\",\n      \"method\": \"In vitro direct interaction assay and co-immunoprecipitation/complex detection in parasite lysate\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro interaction plus co-complex detection in parasite, two orthogonal methods in a single lab\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In the Xenopus oocyte model, PfRCC-PIP (PF3D7_0930800) interacts with endogenous PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1 activity.\",\n      \"method\": \"Xenopus oocyte functional assay with progesterone-induced maturation\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional oocyte assay with progesterone dose-response, single lab, single model system\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The RCC1 motif-containing region of PfRCC-PIP (PF3D7_0930800) interacts with the parasite kinase CDPK7, identifying the protein as a kinase anchoring protein in addition to its role as a phosphatase anchor.\",\n      \"method\": \"Protein interaction assay (region-specific binding to CDPK7)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single interaction assay with no mutagenesis validation or functional consequence defined\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Reverse genetic studies failed to produce viable knock-out parasites for PfRCC-PIP (PF3D7_0930800), suggesting the gene is essential for P. falciparum survival.\",\n      \"method\": \"Reverse genetics / attempted gene knockout\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic essentiality inferred from inability to obtain viable KO parasites, single lab but standard approach\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0930800 (PfRCC-PIP) is an essential P. falciparum protein that functions as a dual kinase- and phosphatase-anchoring scaffold: it directly binds and activates PfPP1 (Protein Phosphatase type-1) and also associates with the kinase CDPK7 via its RCC1 motif-containing region, thereby providing a platform that coordinates phosphorylation/dephosphorylation processes in the parasite.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0930800 (PfRCC-PIP) is an essential Plasmodium falciparum protein that functions as a scaffold coordinating phosphorylation and dephosphorylation, established through direct interaction and functional assays [#0, #1]. It directly binds P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and forms a complex with PfPP1 in parasite lysate, acting as a major regulatory partner of the phosphatase [#0]; in a heterologous Xenopus oocyte system, PfRCC-PIP interacts with endogenous PP1 and synergizes with suboptimal progesterone to drive oocyte maturation, indicating that it activates PP1 activity [#1]. Its RCC1 motif-containing region additionally binds the parasite kinase CDPK7, marking the protein as a kinase-anchoring platform as well as a phosphatase anchor [#2]. Attempted knockout failed to yield viable parasites, indicating the gene is essential for P. falciparum survival [#3]. Beyond these interaction and essentiality findings, no further mechanistic detail — including substrate specificity, structural basis of binding, or the functional consequence of the CDPK7 association — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unknown which regulatory proteins govern PfPP1 in P. falciparum; identifying a direct PfPP1-binding partner established PF3D7_0930800 as a phosphatase-anchoring regulator.\",\n      \"evidence\": \"In vitro direct interaction assay plus co-immunoprecipitation/complex detection in parasite lysate\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The PfPP1-binding motif/interface on PF3D7_0930800 was not mapped by mutagenesis\",\n        \"Substrates dephosphorylated by the PfPP1 complex were not identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the interaction was merely physical or functionally regulatory was open; a heterologous oocyte assay showed PfRCC-PIP activates PP1 activity.\",\n      \"evidence\": \"Xenopus oocyte maturation assay with progesterone dose-response and endogenous PP1\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The activating effect was shown on endogenous Xenopus PP1, not directly quantified on PfPP1 in the parasite\",\n        \"Physiological process in the parasite regulated by this activation is undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unclear whether the protein engaged only phosphatases; binding of its RCC1 motif region to CDPK7 established it as a dual kinase/phosphatase anchor.\",\n      \"evidence\": \"Region-specific protein interaction assay with CDPK7\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single interaction assay without mutagenesis validation or defined functional consequence\",\n        \"No reciprocal or in-parasite confirmation of the CDPK7 association\",\n        \"Whether kinase and phosphatase binding are simultaneous or mutually exclusive is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The biological importance of the gene was unknown; failure to obtain viable knockouts indicated essentiality for blood-stage survival.\",\n      \"evidence\": \"Reverse genetics / attempted gene knockout\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Essentiality inferred from KO failure, not confirmed by conditional knockdown/knockout\",\n        \"The essential stage and process were not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PF3D7_0930800 integrates PfPP1 and CDPK7 activities on shared substrates, and which cellular process depends on this scaffold, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrates of the coordinated kinase/phosphatase platform identified\",\n        \"No structural model of the scaffold or its binding interfaces\",\n        \"Subcellular localization and stage-specific role uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008157\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035304\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\n      \"PfRCC-PIP–PfPP1 complex\"\n    ],\n    \"partners\": [\n      \"PfPP1 (P. falciparum Protein Phosphatase type-1)\",\n      \"CDPK7\"\n    ],\n    \"other_free_text\": [\n      \"Essential for P. falciparum survival (knockout not viable)\",\n      \"Contains an RCC1 motif-containing region that mediates CDPK7 binding\",\n      \"Activates PP1 activity in a heterologous Xenopus oocyte maturation assay\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0930800","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0919900, PF3D7_1123100, PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0930800","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0831500","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0729400","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}