{"gene":"PF3D7_1137400","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_1137400 (PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and is present in complex with PfPP1 in the parasite, establishing it as a major binding partner and regulatory partner of PfPP1.","method":"In vitro interaction assay and co-immunoprecipitation/complex detection in parasite lysate","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding assay plus co-complex detection in parasite, single lab, two orthogonal methods","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PF3D7_1137400 (PfRCC-PIP) interacts with endogenous PP1 in Xenopus oocytes and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating it exerts a regulatory (activating) effect on PP1 activity.","method":"Xenopus oocyte functional assay with progesterone dose–response","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional heterologous assay with synergy readout, single lab, single method","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The RCC1-motif-containing region of PF3D7_1137400 (PfRCC-PIP) interacts with the parasite kinase CDPK7, identifying it as a kinase anchoring protein in addition to its phosphatase-anchoring role.","method":"Protein interaction assay (pulldown/binding assay with RCC1-motif region and CDPK7)","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown/interaction method, no reciprocal validation described in abstract","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies showed that no viable knock-out parasites of PF3D7_1137400 (PfRCC-PIP) could be obtained, suggesting the gene is essential for P. falciparum survival.","method":"Reverse genetics / attempted gene knockout","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single negative genetic result (failure to obtain KO), no conditional KO or complementation described, single lab","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1137400 (PfRCC-PIP) functions as a dual kinase and phosphatase anchoring protein in P. falciparum: it directly binds and positively regulates PP1 phosphatase (demonstrated in vitro and in parasite complexes, and functionally in Xenopus oocytes), and its RCC1 motif region also interacts with the kinase CDPK7, positioning it as a scaffold that coordinates phosphorylation/dephosphorylation; the gene appears essential, as knockout parasites could not be obtained."},"narrative":{"mechanistic_narrative":"PF3D7_1137400 (PfRCC-PIP) is an RCC1-motif-containing regulatory protein of Plasmodium falciparum that functions as a scaffold coordinating phosphatase and kinase activity [PMID:30429842]. It directly binds P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and co-exists in complex with PfPP1 in the parasite, establishing it as a major PfPP1 partner [PMID:30429842]; in a Xenopus oocyte heterologous system it interacts with endogenous PP1 and synergizes with suboptimal progesterone to drive oocyte maturation, indicating it acts as a positive regulator of PP1 activity [PMID:30429842]. Its RCC1-motif region additionally engages the parasite kinase CDPK7, extending its role to that of a kinase-anchoring protein and positioning it to couple phosphorylation with dephosphorylation [PMID:30429842]. Attempts to generate knockout parasites failed, consistent with an essential function [PMID:30429842]. Beyond these interactions and the failed-knockout result, no further mechanistic detail — including in situ localization, substrate specificity, or cell-cycle role — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing that PF3D7_1137400 is a bona fide PfPP1 partner answered whether this RCC1-motif protein physically and functionally associates with the parasite's major phosphatase.","evidence":"In vitro direct interaction assay plus co-immunoprecipitation/complex detection in P. falciparum lysate","pmids":["30429842"],"confidence":"Medium","gaps":["Does not define which region of PfPP1 or PfRCC-PIP mediates binding","No in situ demonstration of where in the parasite the complex forms","Stoichiometry and additional complex members unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"A heterologous functional assay resolved whether the interaction with PP1 is merely physical or regulatory, showing PF3D7_1137400 positively modulates PP1 activity.","evidence":"Xenopus oocyte maturation assay measuring synergy with suboptimal progesterone doses via endogenous PP1","pmids":["30429842"],"confidence":"Medium","gaps":["Activation demonstrated on endogenous Xenopus PP1, not directly on PfPP1 in the parasite","Molecular mechanism of PP1 activation not defined","Physiological substrates dephosphorylated under this regulation unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Identifying a kinase partner tested whether PF3D7_1137400 acts solely on the phosphatase side or bridges kinase and phosphatase activities, revealing a dual anchoring role.","evidence":"Pulldown/binding assay between the RCC1-motif region of PF3D7_1137400 and the kinase CDPK7","pmids":["30429842"],"confidence":"Low","gaps":["Single pulldown without reciprocal validation described","Whether CDPK7 and PfPP1 bind simultaneously or competitively is untested","Functional consequence of the CDPK7 interaction not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Reverse genetics addressed whether the gene is dispensable, indicating essentiality for blood-stage survival.","evidence":"Attempted gene knockout in P. falciparum yielding no viable knockout parasites","pmids":["30429842"],"confidence":"Low","gaps":["Essentiality inferred from failure to obtain KO, not from conditional depletion or complementation","Stage-specific requirement not defined","No phenotype available to link essentiality to the PP1/CDPK7 functions"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PF3D7_1137400 integrates PfPP1 and CDPK7 activity in situ, its substrates, and its cellular localization and cell-cycle role remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional knockdown/knockout phenotype characterized","No substrate or localization data","Simultaneous versus mutually exclusive binding of kinase and phosphatase untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfPP1-containing regulatory complex in P. falciparum"],"partners":["PFPP1 (P. FALCIPARUM PROTEIN PHOSPHATASE TYPE-1)","CDPK7 (P. FALCIPARUM CALCIUM-DEPENDENT PROTEIN KINASE 7)"],"other_free_text":["Contains an RCC1-motif region that mediates the CDPK7 interaction.","Positively regulates PP1 activity in a Xenopus oocyte heterologous assay.","Essential in P. falciparum: no viable knockout parasites obtained."]}},"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":1049,"usd":0.012735,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5763,"output_tokens":2216,"usd":0.042107,"stage2_stop_reason":"end_turn"},"total_usd":0.054842,"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_1137400 (PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and is present in complex with PfPP1 in the parasite, establishing it as a major binding partner and regulatory partner of PfPP1.\",\n      \"method\": \"In vitro 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 binding assay plus co-complex detection in parasite, single lab, two orthogonal methods\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PF3D7_1137400 (PfRCC-PIP) interacts with endogenous PP1 in Xenopus oocytes and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating it exerts a regulatory (activating) effect on PP1 activity.\",\n      \"method\": \"Xenopus oocyte functional assay with progesterone dose–response\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional heterologous assay with synergy readout, 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_1137400 (PfRCC-PIP) interacts with the parasite kinase CDPK7, identifying it as a kinase anchoring protein in addition to its phosphatase-anchoring role.\",\n      \"method\": \"Protein interaction assay (pulldown/binding assay with RCC1-motif region and CDPK7)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown/interaction method, no reciprocal validation described in abstract\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Reverse genetic studies showed that no viable knock-out parasites of PF3D7_1137400 (PfRCC-PIP) could be obtained, suggesting the gene is essential for P. falciparum survival.\",\n      \"method\": \"Reverse genetics / attempted gene knockout\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single negative genetic result (failure to obtain KO), no conditional KO or complementation described, single lab\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1137400 (PfRCC-PIP) functions as a dual kinase and phosphatase anchoring protein in P. falciparum: it directly binds and positively regulates PP1 phosphatase (demonstrated in vitro and in parasite complexes, and functionally in Xenopus oocytes), and its RCC1 motif region also interacts with the kinase CDPK7, positioning it as a scaffold that coordinates phosphorylation/dephosphorylation; the gene appears essential, as knockout parasites could not be obtained.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1137400 (PfRCC-PIP) is an RCC1-motif-containing regulatory protein of Plasmodium falciparum that functions as a scaffold coordinating phosphatase and kinase activity [#0, #2]. It directly binds P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and co-exists in complex with PfPP1 in the parasite, establishing it as a major PfPP1 partner [#0]; in a Xenopus oocyte heterologous system it interacts with endogenous PP1 and synergizes with suboptimal progesterone to drive oocyte maturation, indicating it acts as a positive regulator of PP1 activity [#1]. Its RCC1-motif region additionally engages the parasite kinase CDPK7, extending its role to that of a kinase-anchoring protein and positioning it to couple phosphorylation with dephosphorylation [#2]. Attempts to generate knockout parasites failed, consistent with an essential function [#3]. Beyond these interactions and the failed-knockout result, no further mechanistic detail — including in situ localization, substrate specificity, or cell-cycle role — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing that PF3D7_1137400 is a bona fide PfPP1 partner answered whether this RCC1-motif protein physically and functionally associates with the parasite's major phosphatase.\",\n      \"evidence\": \"In vitro direct interaction assay plus co-immunoprecipitation/complex detection in P. falciparum lysate\",\n      \"pmids\": [\n        \"30429842\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not define which region of PfPP1 or PfRCC-PIP mediates binding\",\n        \"No in situ demonstration of where in the parasite the complex forms\",\n        \"Stoichiometry and additional complex members unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"A heterologous functional assay resolved whether the interaction with PP1 is merely physical or regulatory, showing PF3D7_1137400 positively modulates PP1 activity.\",\n      \"evidence\": \"Xenopus oocyte maturation assay measuring synergy with suboptimal progesterone doses via endogenous PP1\",\n      \"pmids\": [\n        \"30429842\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Activation demonstrated on endogenous Xenopus PP1, not directly on PfPP1 in the parasite\",\n        \"Molecular mechanism of PP1 activation not defined\",\n        \"Physiological substrates dephosphorylated under this regulation unknown\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identifying a kinase partner tested whether PF3D7_1137400 acts solely on the phosphatase side or bridges kinase and phosphatase activities, revealing a dual anchoring role.\",\n      \"evidence\": \"Pulldown/binding assay between the RCC1-motif region of PF3D7_1137400 and the kinase CDPK7\",\n      \"pmids\": [\n        \"30429842\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single pulldown without reciprocal validation described\",\n        \"Whether CDPK7 and PfPP1 bind simultaneously or competitively is untested\",\n        \"Functional consequence of the CDPK7 interaction not measured\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Reverse genetics addressed whether the gene is dispensable, indicating essentiality for blood-stage survival.\",\n      \"evidence\": \"Attempted gene knockout in P. falciparum yielding no viable knockout parasites\",\n      \"pmids\": [\n        \"30429842\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Essentiality inferred from failure to obtain KO, not from conditional depletion or complementation\",\n        \"Stage-specific requirement not defined\",\n        \"No phenotype available to link essentiality to the PP1/CDPK7 functions\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PF3D7_1137400 integrates PfPP1 and CDPK7 activity in situ, its substrates, and its cellular localization and cell-cycle role remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No conditional knockdown/knockout phenotype characterized\",\n        \"No substrate or localization data\",\n        \"Simultaneous versus mutually exclusive binding of kinase and phosphatase untested\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0019888\",\n        \"supporting_discovery_ids\": [0, 1]\n      },\n      {\n        \"term_id\": \"GO:0008157\",\n        \"supporting_discovery_ids\": [2]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006470\",\n        \"supporting_discovery_ids\": [0, 1]\n      }\n    ],\n    \"complexes\": [\n      \"PfPP1-containing regulatory complex in P. falciparum\"\n    ],\n    \"partners\": [\n      \"PfPP1 (P. falciparum Protein Phosphatase type-1)\",\n      \"CDPK7 (P. falciparum calcium-dependent protein kinase 7)\"\n    ],\n    \"other_free_text\": [\n      \"Contains an RCC1-motif region that mediates the CDPK7 interaction.\",\n      \"Positively regulates PP1 activity in a Xenopus oocyte heterologous assay.\",\n      \"Essential in P. falciparum: no viable knockout parasites obtained.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1137400","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_1137400","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0911300","name":null,"product":"UVB-resistance protein UVR8 homologue, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0935600","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}