{"gene":"PF3D7_0418600","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_0418600 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and forms a complex with PfPP1 in the parasite, acting as a major partner of PfPP1.","method":"In vitro binding assay and co-immunoprecipitation in P. falciparum parasites","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction shown both in vitro and in parasite lysate by a single lab with two orthogonal methods","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PF3D7_0418600 (PfRCC-PIP) interacts with endogenous PP1 in the Xenopus oocyte model and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1.","method":"Xenopus oocyte functional assay","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — heterologous functional assay with clear phenotypic readout, single lab","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies failed to produce viable knock-out parasites for PF3D7_0418600 (PfRCC-PIP), suggesting it is essential for parasite viability.","method":"Reverse genetics (attempted gene knock-out)","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — standard essentiality inference from failed KO, single lab, single method","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The RCC1-motif-containing region of PF3D7_0418600 (PfRCC-PIP) directly interacts with the parasite kinase CDPK7, indicating that this protein serves as both a kinase and a phosphatase anchoring protein.","method":"In vitro protein interaction assay (pulldown with defined protein region)","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, single pulldown method but domain-level resolution adds specificity","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0418600 (PfRCC-PIP) is an essential P. falciparum scaffolding protein that directly binds both the phosphatase PfPP1 (via in vitro and in-parasite interaction) and the kinase CDPK7 (via its RCC1-motif region), thereby serving as a dual kinase/phosphatase anchoring platform that positively regulates PP1 activity and, by extension, phosphorylation/dephosphorylation signaling in the parasite."},"narrative":{"mechanistic_narrative":"PF3D7_0418600 (PfRCC-PIP) is an essential P. falciparum scaffolding protein that functions as a dual anchoring platform for a kinase and a phosphatase [PMID:30429842]. It directly binds the parasite phosphatase PfPP1 both in vitro and as a complex in parasite lysate, serving as a major PfPP1 partner [PMID:30429842], and it acts as a positive regulator of PP1 activity — in the heterologous Xenopus oocyte system it interacts with endogenous PP1 and synergizes with suboptimal progesterone doses to trigger oocyte maturation [PMID:30429842]. Through its RCC1-motif-containing region it additionally binds the calcium-dependent kinase CDPK7, positioning the protein to co-anchor kinase and phosphatase activities [PMID:30429842]. Attempted gene knock-out failed to yield viable parasites, indicating that PF3D7_0418600 is essential for parasite viability [PMID:30429842]. Beyond these interactions and the essentiality inference, no further mechanistic detail — including physiological substrates, structural basis of binding, or the parasite processes it regulates — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing that PF3D7_0418600 is a bona fide PfPP1 partner answered whether this putative RCC1-motif protein physically engages the phosphatase machinery.","evidence":"In vitro binding assay plus co-immunoprecipitation from P. falciparum parasites","pmids":["30429842"],"confidence":"Medium","gaps":["Binding interface and stoichiometry of the PfPP1 complex not defined","Single lab; interaction not independently replicated","No identification of substrates dephosphorylated by the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The Xenopus oocyte assay addressed whether the interaction is functionally regulatory, showing PF3D7_0418600 acts as a positive modulator of PP1 activity rather than a passive binding partner.","evidence":"Heterologous Xenopus oocyte maturation assay with suboptimal progesterone","pmids":["30429842"],"confidence":"Medium","gaps":["Activation demonstrated in a heterologous system, not on native PfPP1 substrates in parasite","Mechanism by which it enhances PP1 activity unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Failed knock-out attempts addressed whether the gene is dispensable, indicating it is essential for asexual parasite viability.","evidence":"Reverse genetics (attempted gene knock-out) in P. falciparum","pmids":["30429842"],"confidence":"Medium","gaps":["Essentiality inferred from failed KO, not confirmed by conditional depletion","Which molecular function underlies essentiality is unresolved","Stage-specific requirement not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Mapping the CDPK7 interaction to the RCC1-motif region addressed whether PF3D7_0418600 links a kinase as well as a phosphatase, establishing it as a dual kinase/phosphatase anchoring protein.","evidence":"In vitro pulldown using the defined RCC1-motif-containing region","pmids":["30429842"],"confidence":"Medium","gaps":["CDPK7 binding shown in vitro only; not validated in parasite","Whether PfPP1 and CDPK7 occupy the scaffold simultaneously is untested","Functional consequence of CDPK7 anchoring not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological substrates, parasite processes, and structural basis by which PF3D7_0418600 coordinates PfPP1 and CDPK7 remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No native substrate of the PP1/CDPK7 scaffold identified","No structural model of the interactions or the RCC1-motif region","Cellular process regulated by the complex is uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PF3D7_0418600–PfPP1 complex (in parasite)"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE-1)","CDPK7 (CALCIUM-DEPENDENT PROTEIN KINASE 7)"],"other_free_text":["Directly binds PfPP1 in vitro and in P. falciparum parasites [#0]","Positively regulates PP1 activity in Xenopus oocyte assay, synergizing with suboptimal progesterone [#1]","RCC1-motif-containing region mediates direct CDPK7 binding, making it a dual kinase/phosphatase anchoring protein [#3]","Essential for parasite viability; knock-out not obtained [#2]"]}},"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},{"pmid":"39950472","id":"PMC_39950472","title":"A Potential Regulatory Network of Selected Human Erythrocytic miRNAs with Plasmodium falciparum 3D7 mRNAs: A Computational Analysis.","date":"2025","source":"MicroRNA (Shariqah, United Arab Emirates)","url":"https://pubmed.ncbi.nlm.nih.gov/39950472","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PFD0900w"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4104,"output_tokens":991,"usd":0.013588,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5674,"output_tokens":2182,"usd":0.04146,"stage2_stop_reason":"end_turn"},"total_usd":0.055048,"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\": 2018,\n      \"finding\": \"PF3D7_0418600 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and forms a complex with PfPP1 in the parasite, acting as a major partner of PfPP1.\",\n      \"method\": \"In vitro binding assay and co-immunoprecipitation in P. falciparum parasites\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction shown both in vitro and in parasite lysate by a single lab with two orthogonal methods\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PF3D7_0418600 (PfRCC-PIP) interacts with endogenous PP1 in the Xenopus oocyte model and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1.\",\n      \"method\": \"Xenopus oocyte functional assay\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — heterologous functional assay with clear phenotypic readout, single lab\",\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 PF3D7_0418600 (PfRCC-PIP), suggesting it is essential for parasite viability.\",\n      \"method\": \"Reverse genetics (attempted gene knock-out)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — standard essentiality inference from failed KO, single lab, single method\",\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 PF3D7_0418600 (PfRCC-PIP) directly interacts with the parasite kinase CDPK7, indicating that this protein serves as both a kinase and a phosphatase anchoring protein.\",\n      \"method\": \"In vitro protein interaction assay (pulldown with defined protein region)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, single pulldown method but domain-level resolution adds specificity\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0418600 (PfRCC-PIP) is an essential P. falciparum scaffolding protein that directly binds both the phosphatase PfPP1 (via in vitro and in-parasite interaction) and the kinase CDPK7 (via its RCC1-motif region), thereby serving as a dual kinase/phosphatase anchoring platform that positively regulates PP1 activity and, by extension, phosphorylation/dephosphorylation signaling in the parasite.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0418600 (PfRCC-PIP) is an essential P. falciparum scaffolding protein that functions as a dual anchoring platform for a kinase and a phosphatase [#0, #3]. It directly binds the parasite phosphatase PfPP1 both in vitro and as a complex in parasite lysate, serving as a major PfPP1 partner [#0], and it acts as a positive regulator of PP1 activity — in the heterologous Xenopus oocyte system it interacts with endogenous PP1 and synergizes with suboptimal progesterone doses to trigger oocyte maturation [#1]. Through its RCC1-motif-containing region it additionally binds the calcium-dependent kinase CDPK7, positioning the protein to co-anchor kinase and phosphatase activities [#3]. Attempted gene knock-out failed to yield viable parasites, indicating that PF3D7_0418600 is essential for parasite viability [#2]. Beyond these interactions and the essentiality inference, no further mechanistic detail — including physiological substrates, structural basis of binding, or the parasite processes it regulates — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing that PF3D7_0418600 is a bona fide PfPP1 partner answered whether this putative RCC1-motif protein physically engages the phosphatase machinery.\",\n      \"evidence\": \"In vitro binding assay plus co-immunoprecipitation from P. falciparum parasites\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding interface and stoichiometry of the PfPP1 complex not defined\",\n        \"Single lab; interaction not independently replicated\",\n        \"No identification of substrates dephosphorylated by the complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The Xenopus oocyte assay addressed whether the interaction is functionally regulatory, showing PF3D7_0418600 acts as a positive modulator of PP1 activity rather than a passive binding partner.\",\n      \"evidence\": \"Heterologous Xenopus oocyte maturation assay with suboptimal progesterone\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Activation demonstrated in a heterologous system, not on native PfPP1 substrates in parasite\",\n        \"Mechanism by which it enhances PP1 activity unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Failed knock-out attempts addressed whether the gene is dispensable, indicating it is essential for asexual parasite viability.\",\n      \"evidence\": \"Reverse genetics (attempted gene knock-out) in P. falciparum\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Essentiality inferred from failed KO, not confirmed by conditional depletion\",\n        \"Which molecular function underlies essentiality is unresolved\",\n        \"Stage-specific requirement not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapping the CDPK7 interaction to the RCC1-motif region addressed whether PF3D7_0418600 links a kinase as well as a phosphatase, establishing it as a dual kinase/phosphatase anchoring protein.\",\n      \"evidence\": \"In vitro pulldown using the defined RCC1-motif-containing region\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"CDPK7 binding shown in vitro only; not validated in parasite\",\n        \"Whether PfPP1 and CDPK7 occupy the scaffold simultaneously is untested\",\n        \"Functional consequence of CDPK7 anchoring not measured\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological substrates, parasite processes, and structural basis by which PF3D7_0418600 coordinates PfPP1 and CDPK7 remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No native substrate of the PP1/CDPK7 scaffold identified\",\n        \"No structural model of the interactions or the RCC1-motif region\",\n        \"Cellular process regulated by the complex is uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004864\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0019903\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0030234\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035556\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"complexes\": [\n      \"PF3D7_0418600–PfPP1 complex (in parasite)\"\n    ],\n    \"partners\": [\n      \"PfPP1 (Protein Phosphatase type-1)\",\n      \"CDPK7 (calcium-dependent protein kinase 7)\"\n    ],\n    \"other_free_text\": [\n      \"Directly binds PfPP1 in vitro and in P. falciparum parasites [#0]\",\n      \"Positively regulates PP1 activity in Xenopus oocyte assay, synergizing with suboptimal progesterone [#1]\",\n      \"RCC1-motif-containing region mediates direct CDPK7 binding, making it a dual kinase/phosphatase anchoring protein [#3]\",\n      \"Essential for parasite viability; knock-out not obtained [#2]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0418600","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_0418600","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0720700","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0511300","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}