{"gene":"PF3D7_0919900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_0919900 (RCC-PIP) directly interacts with PfPP1 in vitro and is present in complex with PfPP1 in P. falciparum parasite extracts. In a Xenopus oocyte model, RCC-PIP interacts with endogenous PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating/modulatory) effect on PP1. Reverse genetic studies failed to produce viable knock-out parasites, suggesting an essential role in blood-stage survival. Additionally, the RCC1-motif-containing region of RCC-PIP was shown to interact with the parasite calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein.","method":"In vitro pull-down, co-immunoprecipitation from parasite extracts, Xenopus oocyte functional assay, reverse genetics (failed KO), direct binding assay with recombinant CDPK7","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP confirmed complex in parasite, in vitro direct interaction, and Xenopus functional assay; single lab with multiple orthogonal methods but no structural validation or mutagenesis of binding motifs reported in this abstract","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RCC-PIP (PF3D7_0919900) is a dual-anchoring scaffold protein in P. falciparum that physically associates with both the phosphatase PfPP1 (via a direct interaction confirmed in vitro and in parasite extracts) and the kinase CDPK7 (via its RCC1-repeat region), modulates PP1 activity in a heterologous oocyte system, and appears essential for intraerythrocytic parasite survival, though its precise biochemical mechanism and pathway position remain to be defined."},"narrative":{"mechanistic_narrative":"RCC-PIP (PF3D7_0919900) is a dual-anchoring scaffold protein in Plasmodium falciparum that bridges a phosphatase and a kinase, and appears essential for blood-stage parasite survival [PMID:30429842]. It directly interacts with the phosphatase PfPP1 in vitro and is present in complex with PfPP1 in parasite extracts; in a Xenopus oocyte system it binds endogenous PP1 and, in synergy with suboptimal progesterone, triggers oocyte maturation, indicating a regulatory, activating effect on PP1 [PMID:30429842]. Its RCC1-motif-containing region additionally binds the calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein [PMID:30429842]. Reverse genetic studies failed to yield viable knock-out parasites, consistent with an essential role in intraerythrocytic survival [PMID:30429842]. Beyond [PMID:30429842], no further mechanistic detail — including structural basis of binding, mutagenesis of interaction motifs, or defined pathway position — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether PF3D7_0919900 acts as a regulator of the parasite phosphatase PfPP1 was unknown; this work established it as a direct PP1-interacting protein that modulates PP1 activity and simultaneously anchors the kinase CDPK7, defining it as a dual kinase/phosphatase scaffold essential for blood-stage growth.","evidence":"In vitro pull-down and reciprocal co-immunoprecipitation from parasite extracts, Xenopus oocyte functional maturation assay, direct binding of recombinant CDPK7, and failed knock-out by reverse genetics","pmids":["30429842"],"confidence":"Medium","gaps":["No structural model or mutagenesis of the PP1- or CDPK7-binding motifs to define contact residues","The biochemical consequence of RCC-PIP anchoring on CDPK7 activity and on PP1 in the native parasite is undefined","The pathway context and substrates coordinated by this kinase-phosphatase scaffold remain unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How RCC-PIP integrates PfPP1 and CDPK7 signaling to support intraerythrocytic survival, and which downstream substrates it regulates, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No conditional knockdown to define the essential function underlying the failed knock-out","No identification of substrates or the cellular process controlled by the scaffold","No structural characterization of the RCC1-repeat interaction interfaces"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RCC-PIP–PfPP1 complex (in parasite extracts and in vitro)"],"partners":["PFPP1 (PROTEIN PHOSPHATASE 1)","CDPK7 (CALCIUM-DEPENDENT PROTEIN KINASE 7)"],"other_free_text":["Failed knock-out by reverse genetics indicates an essential role in P. falciparum blood-stage survival [#0].","In a Xenopus oocyte system, RCC-PIP synergizes with suboptimal progesterone to trigger maturation, indicating a modulatory/activating effect on endogenous PP1 [#0].","The RCC1-motif-containing region mediates the interaction with CDPK7 [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12057017","id":"PMC_12057017","title":"Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference.","date":"2002","source":"Malaria 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transmission.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/40823845","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP1","PfPP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12897,"output_tokens":576,"usd":0.023665,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5160,"output_tokens":1528,"usd":0.032,"stage2_stop_reason":"end_turn"},"total_usd":0.055665,"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_0919900 (RCC-PIP) directly interacts with PfPP1 in vitro and is present in complex with PfPP1 in P. falciparum parasite extracts. In a Xenopus oocyte model, RCC-PIP interacts with endogenous PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating/modulatory) effect on PP1. Reverse genetic studies failed to produce viable knock-out parasites, suggesting an essential role in blood-stage survival. Additionally, the RCC1-motif-containing region of RCC-PIP was shown to interact with the parasite calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein.\",\n      \"method\": \"In vitro pull-down, co-immunoprecipitation from parasite extracts, Xenopus oocyte functional assay, reverse genetics (failed KO), direct binding assay with recombinant CDPK7\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP confirmed complex in parasite, in vitro direct interaction, and Xenopus functional assay; single lab with multiple orthogonal methods but no structural validation or mutagenesis of binding motifs reported in this abstract\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"RCC-PIP (PF3D7_0919900) is a dual-anchoring scaffold protein in P. falciparum that physically associates with both the phosphatase PfPP1 (via a direct interaction confirmed in vitro and in parasite extracts) and the kinase CDPK7 (via its RCC1-repeat region), modulates PP1 activity in a heterologous oocyte system, and appears essential for intraerythrocytic parasite survival, though its precise biochemical mechanism and pathway position remain to be defined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RCC-PIP (PF3D7_0919900) is a dual-anchoring scaffold protein in Plasmodium falciparum that bridges a phosphatase and a kinase, and appears essential for blood-stage parasite survival [#0]. It directly interacts with the phosphatase PfPP1 in vitro and is present in complex with PfPP1 in parasite extracts; in a Xenopus oocyte system it binds endogenous PP1 and, in synergy with suboptimal progesterone, triggers oocyte maturation, indicating a regulatory, activating effect on PP1 [#0]. Its RCC1-motif-containing region additionally binds the calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein [#0]. Reverse genetic studies failed to yield viable knock-out parasites, consistent with an essential role in intraerythrocytic survival [#0]. Beyond [#0], no further mechanistic detail — including structural basis of binding, mutagenesis of interaction motifs, or defined pathway position — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether PF3D7_0919900 acts as a regulator of the parasite phosphatase PfPP1 was unknown; this work established it as a direct PP1-interacting protein that modulates PP1 activity and simultaneously anchors the kinase CDPK7, defining it as a dual kinase/phosphatase scaffold essential for blood-stage growth.\",\n      \"evidence\": \"In vitro pull-down and reciprocal co-immunoprecipitation from parasite extracts, Xenopus oocyte functional maturation assay, direct binding of recombinant CDPK7, and failed knock-out by reverse genetics\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Multiple orthogonal methods from a single lab; no structural validation or binding-motif mutagenesis reported\",\n      \"gaps\": [\n        \"No structural model or mutagenesis of the PP1- or CDPK7-binding motifs to define contact residues\",\n        \"The biochemical consequence of RCC-PIP anchoring on CDPK7 activity and on PP1 in the native parasite is undefined\",\n        \"The pathway context and substrates coordinated by this kinase-phosphatase scaffold remain unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RCC-PIP integrates PfPP1 and CDPK7 signaling to support intraerythrocytic survival, and which downstream substrates it regulates, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No conditional knockdown to define the essential function underlying the failed knock-out\",\n        \"No identification of substrates or the cellular process controlled by the scaffold\",\n        \"No structural characterization of the RCC1-repeat interaction interfaces\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004864\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019902\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"RCC-PIP–PfPP1 complex (in parasite extracts and in vitro)\"],\n    \"partners\": [\"PfPP1 (protein phosphatase 1)\", \"CDPK7 (calcium-dependent protein kinase 7)\"],\n    \"other_free_text\": [\n      \"Failed knock-out by reverse genetics indicates an essential role in P. falciparum blood-stage survival [#0].\",\n      \"In a Xenopus oocyte system, RCC-PIP synergizes with suboptimal progesterone to trigger maturation, indicating a modulatory/activating effect on endogenous PP1 [#0].\",\n      \"The RCC1-motif-containing region mediates the interaction with CDPK7 [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0919900","name":null,"product":"regulator of chromosome condensation-PP1-interacting protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0820800","name":null,"product":"regulator of chromosome condensation-PP1-interacting protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0717900","name":null,"product":"regulator of chromosome condensation-PP1-interacting protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RCC-PIP","evaluation":null}