{"gene":"PF3D7_1356600","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_1356600 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and is present in a complex with PfPP1 in the parasite, establishing it as a major binding partner of PfPP1.","method":"In vitro binding assay and co-immunoprecipitation from parasite lysate","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro interaction plus co-IP from parasite, two orthogonal methods, single lab","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfRCC-PIP (PF3D7_1356600) interacts with endogenous Xenopus PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1 phosphatase activity.","method":"Xenopus oocyte functional assay","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional assay in heterologous system (Xenopus), single lab, single method","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The RCC1-motif-containing region of PfRCC-PIP (PF3D7_1356600) interacts with the parasite kinase CDPK7, identifying it as a kinase anchoring protein in addition to its role as a phosphatase anchor.","method":"Protein interaction assay (pulldown/binding assay with RCC1-containing protein region)","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single interaction assay with a protein fragment, no mutagenesis or orthogonal validation reported","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies (attempted knock-out) indicated that PfRCC-PIP (PF3D7_1356600) is essential for parasite viability, as no viable knock-out parasites could be obtained.","method":"Reverse genetics / attempted gene knock-out","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — negative selection result (failure to obtain KO) from a single lab, no conditional KO or complementation reported","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1356600 (PfRCC-PIP) functions as a dual kinase/phosphatase anchoring protein in P. falciparum: its RCC1-motif region directly binds and activates PP1 phosphatase (in vitro and in the parasite) and also interacts with the kinase CDPK7, suggesting it serves as a scaffold to coordinate phosphorylation/dephosphorylation events; the protein appears essential for parasite viability."},"narrative":{"mechanistic_narrative":"PF3D7_1356600 (PfRCC-PIP) is an RCC1-motif-containing regulatory protein of Plasmodium falciparum that functions as a phosphatase-anchoring partner of the parasite Protein Phosphatase type-1 (PfPP1), which it binds directly in vitro and forms a complex with in the parasite [PMID:30429842]. In a heterologous Xenopus oocyte system, PfRCC-PIP interacts with endogenous PP1 and synergizes with suboptimal progesterone to promote oocyte maturation, indicating it acts as a positive regulator of PP1 activity [PMID:30429842]. Its RCC1-motif region additionally binds the parasite calcium-dependent protein kinase CDPK7, positioning PfRCC-PIP as a scaffold that could coordinate both kinase and phosphatase activities [PMID:30429842], and attempted knock-out failed to yield viable parasites, consistent with an essential role [PMID:30429842]. Beyond these interaction and viability findings from a single study, no further mechanistic detail — substrate specificity, structural basis of binding, or in-parasite regulatory targets — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Established that PF3D7_1356600 is a direct binding partner of the parasite phosphatase PfPP1, defining its first molecular interaction and its identity as a phosphatase-associated protein.","evidence":"In vitro binding assay and co-immunoprecipitation from P. falciparum lysate","pmids":["30429842"],"confidence":"Medium","gaps":["The binding interface and RCC1-motif requirement for PfPP1 interaction were not mapped by mutagenesis","Stoichiometry and other components of the parasite PfPP1 complex are undefined","No in-parasite dephosphorylation substrate was identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Addressed whether the PfPP1 interaction is merely structural or regulatory, showing PfRCC-PIP activates PP1 in a functional context.","evidence":"Xenopus oocyte maturation assay with endogenous PP1 and suboptimal progesterone doses","pmids":["30429842"],"confidence":"Medium","gaps":["Activation was shown against Xenopus PP1 in a heterologous system, not against PfPP1 in the parasite","The biochemical mechanism of PP1 activation (versus canonical inhibition) is unresolved","No direct phosphatase activity measurement on defined substrates"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Extended the protein's role beyond phosphatase anchoring by identifying a kinase partner, raising the possibility of a dual scaffolding function.","evidence":"Pulldown/binding assay of the RCC1-motif-containing region with the kinase CDPK7","pmids":["30429842"],"confidence":"Low","gaps":["Single interaction assay with a protein fragment, no mutagenesis or orthogonal/reciprocal validation","Whether PfPP1 and CDPK7 bind simultaneously or competitively is unknown","Functional consequence of the CDPK7 interaction in the parasite is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Assessed the biological importance of the gene, indicating it is required for blood-stage parasite viability.","evidence":"Reverse genetics / attempted gene knock-out (failure to recover viable KO parasites)","pmids":["30429842"],"confidence":"Low","gaps":["Negative-selection inference from failure to obtain KO; no conditional knock-out or complementation to confirm essentiality","The essential cellular process the protein supports is not defined","Stage-specific requirements were not examined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown how PfRCC-PIP coordinates PfPP1 and CDPK7 activities in the parasite, what phosphoprotein substrates it governs, and whether its scaffolding function underlies its essentiality.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in-parasite substrate or dephosphorylation/phosphorylation target identified","No structural model or mapped binding interfaces","Localization and cell-cycle timing of the protein not characterized in the corpus"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfPP1-containing complex (with PF3D7_1356600) [#0]"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE-1) [#0, #1]","CDPK7 [#2]"],"other_free_text":["Contains an RCC1-motif region that mediates the CDPK7 interaction [#2].","Acts as a positive regulator of PP1 activity in a Xenopus oocyte maturation assay [#1].","Essential for P. falciparum viability by failure to recover knock-out parasites [#3].","All current evidence derives from a single 2018 study; no localization data available in the corpus."]}},"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":1006,"usd":0.012412,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5699,"output_tokens":2193,"usd":0.04166,"stage2_stop_reason":"end_turn"},"total_usd":0.054072,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PF3D7_1356600 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and is present in a complex with PfPP1 in the parasite, establishing it as a major binding partner of PfPP1.\",\n      \"method\": \"In vitro binding assay and co-immunoprecipitation from parasite lysate\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro interaction plus co-IP from parasite, two orthogonal methods, single lab\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfRCC-PIP (PF3D7_1356600) interacts with endogenous Xenopus PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating) effect on PP1 phosphatase activity.\",\n      \"method\": \"Xenopus oocyte functional assay\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional assay in heterologous system (Xenopus), 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 PfRCC-PIP (PF3D7_1356600) interacts with the parasite kinase CDPK7, identifying it as a kinase anchoring protein in addition to its role as a phosphatase anchor.\",\n      \"method\": \"Protein interaction assay (pulldown/binding assay with RCC1-containing protein region)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single interaction assay with a protein fragment, no mutagenesis or orthogonal validation reported\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Reverse genetic studies (attempted knock-out) indicated that PfRCC-PIP (PF3D7_1356600) is essential for parasite viability, as no viable knock-out parasites could be obtained.\",\n      \"method\": \"Reverse genetics / attempted gene knock-out\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — negative selection result (failure to obtain KO) from a single lab, no conditional KO or complementation reported\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1356600 (PfRCC-PIP) functions as a dual kinase/phosphatase anchoring protein in P. falciparum: its RCC1-motif region directly binds and activates PP1 phosphatase (in vitro and in the parasite) and also interacts with the kinase CDPK7, suggesting it serves as a scaffold to coordinate phosphorylation/dephosphorylation events; the protein appears essential for parasite viability.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1356600 (PfRCC-PIP) is an RCC1-motif-containing regulatory protein of Plasmodium falciparum that functions as a phosphatase-anchoring partner of the parasite Protein Phosphatase type-1 (PfPP1), which it binds directly in vitro and forms a complex with in the parasite [#0]. In a heterologous Xenopus oocyte system, PfRCC-PIP interacts with endogenous PP1 and synergizes with suboptimal progesterone to promote oocyte maturation, indicating it acts as a positive regulator of PP1 activity [#1]. Its RCC1-motif region additionally binds the parasite calcium-dependent protein kinase CDPK7, positioning PfRCC-PIP as a scaffold that could coordinate both kinase and phosphatase activities [#2], and attempted knock-out failed to yield viable parasites, consistent with an essential role [#3]. Beyond these interaction and viability findings from a single study, no further mechanistic detail — substrate specificity, structural basis of binding, or in-parasite regulatory targets — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established that PF3D7_1356600 is a direct binding partner of the parasite phosphatase PfPP1, defining its first molecular interaction and its identity as a phosphatase-associated protein.\",\n      \"evidence\": \"In vitro binding assay and co-immunoprecipitation from P. falciparum lysate\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The binding interface and RCC1-motif requirement for PfPP1 interaction were not mapped by mutagenesis\",\n        \"Stoichiometry and other components of the parasite PfPP1 complex are undefined\",\n        \"No in-parasite dephosphorylation substrate was identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Addressed whether the PfPP1 interaction is merely structural or regulatory, showing PfRCC-PIP activates PP1 in a functional context.\",\n      \"evidence\": \"Xenopus oocyte maturation assay with endogenous PP1 and suboptimal progesterone doses\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Activation was shown against Xenopus PP1 in a heterologous system, not against PfPP1 in the parasite\",\n        \"The biochemical mechanism of PP1 activation (versus canonical inhibition) is unresolved\",\n        \"No direct phosphatase activity measurement on defined substrates\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended the protein's role beyond phosphatase anchoring by identifying a kinase partner, raising the possibility of a dual scaffolding function.\",\n      \"evidence\": \"Pulldown/binding assay of the RCC1-motif-containing region with the kinase CDPK7\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single interaction assay with a protein fragment, no mutagenesis or orthogonal/reciprocal validation\",\n        \"Whether PfPP1 and CDPK7 bind simultaneously or competitively is unknown\",\n        \"Functional consequence of the CDPK7 interaction in the parasite is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Assessed the biological importance of the gene, indicating it is required for blood-stage parasite viability.\",\n      \"evidence\": \"Reverse genetics / attempted gene knock-out (failure to recover viable KO parasites)\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Negative-selection inference from failure to obtain KO; no conditional knock-out or complementation to confirm essentiality\",\n        \"The essential cellular process the protein supports is not defined\",\n        \"Stage-specific requirements were not examined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how PfRCC-PIP coordinates PfPP1 and CDPK7 activities in the parasite, what phosphoprotein substrates it governs, and whether its scaffolding function underlies its essentiality.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in-parasite substrate or dephosphorylation/phosphorylation target identified\",\n        \"No structural model or mapped binding interfaces\",\n        \"Localization and cell-cycle timing of the protein not characterized in the corpus\"\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\": [1]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006470\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"PfPP1-containing complex (with PF3D7_1356600) [#0]\"],\n    \"partners\": [\"PfPP1 (Protein Phosphatase type-1) [#0, #1]\", \"CDPK7 [#2]\"],\n    \"other_free_text\": [\n      \"Contains an RCC1-motif region that mediates the CDPK7 interaction [#2].\",\n      \"Acts as a positive regulator of PP1 activity in a Xenopus oocyte maturation assay [#1].\",\n      \"Essential for P. falciparum viability by failure to recover knock-out parasites [#3].\",\n      \"All current evidence derives from a single 2018 study; no localization data available in the corpus.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1356600","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_1356600","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1132900","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1114900","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}