{"gene":"PF3D7_0711500","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2012,"finding":"PF3D7_0711500 (a putative regulator of chromosome condensation) was experimentally identified as a nuclear protein in P. falciparum by organellar proteomics and confirmed by transgenic cell line validation, establishing its nuclear localization.","method":"High-accuracy mass spectrometry of nuclear fractions combined with experimental validation using transgenic cell lines expressing tagged protein","journal":"Genome biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular fractionation followed by MS identification and validation with 30 transgenic lines, but mechanistic functional consequence of nuclear localization not individually characterized for this protein","pmids":["23181666"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PF3D7_0711500 (named PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and in complex in the parasite; the protein region containing RCC1 motifs also interacts with the parasite kinase CDPK7, establishing PfRCC-PIP as both a phosphatase- and kinase-anchoring protein.","method":"In vitro binding assay (direct interaction with PfPP1), co-immunoprecipitation from parasite lysate, Xenopus oocyte functional assay (PP1 regulatory effect), and reverse genetics (attempted knockout — no viable parasites obtained)","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal in vitro and in parasite interaction data for PfPP1, functional oocyte assay, and interaction with CDPK7; single lab with multiple orthogonal methods","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies (attempted knockout) of PfRCC-PIP (PF3D7_0711500) failed to yield viable parasites, 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 lab, single method (failed KO), no conditional system to confirm essentiality rigorously","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0711500 (PfRCC-PIP) is a nuclear-localized protein in P. falciparum that acts as a dual anchoring scaffold, directly binding both the phosphatase PfPP1 (in vitro and in the parasite) and the kinase CDPK7 via its RCC1 motifs, thereby potentially coordinating phosphorylation/dephosphorylation processes; it appears to be essential for parasite viability based on failed knockout attempts."},"narrative":{"mechanistic_narrative":"PF3D7_0711500 is a nuclear protein of Plasmodium falciparum, identified by nuclear-fraction proteomics and confirmed with tagged transgenic lines [PMID:23181666]. Named PfRCC-PIP, it functions as a dual anchoring scaffold: it directly binds the parasite Protein Phosphatase type-1 (PfPP1) both in vitro and in the parasite, and the region containing its RCC1 motifs also engages the parasite kinase CDPK7, positioning it to bridge a phosphatase and a kinase [PMID:30429842]. Attempted knockout yielded no viable parasites, consistent with a role essential for asexual survival [PMID:30429842]. Beyond these interaction and localization findings, the downstream substrates and the biological consequence of the PfPP1/CDPK7 anchoring have not been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Whether PF3D7_0711500 resides in a specific subcellular compartment was unknown; establishing nuclear localization provided the first functional context for this putative RCC1-motif protein.","evidence":"High-accuracy mass spectrometry of P. falciparum nuclear fractions with transgenic tagged-line validation","pmids":["23181666"],"confidence":"Medium","gaps":["Functional consequence of nuclear localization not tested for this protein","No cell-cycle or chromatin association demonstrated","Interaction partners unidentified at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"It was unknown what molecular partners PF3D7_0711500 engaged; direct binding to PfPP1 and to CDPK7 via its RCC1-motif region established it as a dual kinase/phosphatase anchoring scaffold (PfRCC-PIP).","evidence":"In vitro binding assay, co-immunoprecipitation from parasite lysate, and Xenopus oocyte PP1 regulatory assay","pmids":["30429842"],"confidence":"Medium","gaps":["Substrates dephosphorylated/phosphorylated within the complex not identified","Biological process coordinated by the anchoring not defined","Structural basis of RCC1-motif binding to CDPK7 not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether the gene is required for parasite growth was untested; failure to recover knockout parasites indicated it is likely essential for survival.","evidence":"Reverse genetics / attempted gene knockout in P. falciparum","pmids":["30429842"],"confidence":"Low","gaps":["Single failed-KO approach without a conditional system to rigorously confirm essentiality","Stage-specific requirement not defined","No phenotype from controlled depletion"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The downstream substrates and the cellular process coordinated by the PfPP1/CDPK7 anchoring function of PF3D7_0711500 remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate of the anchored phosphatase/kinase identified","No conditional-depletion phenotype linking the scaffold to a specific pathway","No structural model of the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfRCC-PIP–PfPP1 complex in the parasite [#1]"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE-1) [#1]","CDPK7 [#1]"],"other_free_text":["Contains RCC1 motifs that mediate the interaction with CDPK7 [#1]","Attempted knockout produced no viable parasites, indicating likely essentiality [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23181666","id":"PMC_23181666","title":"Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum.","date":"2012","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/23181666","citation_count":119,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":3737,"output_tokens":898,"usd":0.012341,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5574,"output_tokens":1651,"usd":0.034572,"stage2_stop_reason":"end_turn"},"total_usd":0.046913,"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\": 2012,\n      \"finding\": \"PF3D7_0711500 (a putative regulator of chromosome condensation) was experimentally identified as a nuclear protein in P. falciparum by organellar proteomics and confirmed by transgenic cell line validation, establishing its nuclear localization.\",\n      \"method\": \"High-accuracy mass spectrometry of nuclear fractions combined with experimental validation using transgenic cell lines expressing tagged protein\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular fractionation followed by MS identification and validation with 30 transgenic lines, but mechanistic functional consequence of nuclear localization not individually characterized for this protein\",\n      \"pmids\": [\"23181666\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PF3D7_0711500 (named PfRCC-PIP) directly interacts with P. falciparum Protein Phosphatase type-1 (PfPP1) in vitro and in complex in the parasite; the protein region containing RCC1 motifs also interacts with the parasite kinase CDPK7, establishing PfRCC-PIP as both a phosphatase- and kinase-anchoring protein.\",\n      \"method\": \"In vitro binding assay (direct interaction with PfPP1), co-immunoprecipitation from parasite lysate, Xenopus oocyte functional assay (PP1 regulatory effect), and reverse genetics (attempted knockout — no viable parasites obtained)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal in vitro and in parasite interaction data for PfPP1, functional oocyte assay, and interaction with CDPK7; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Reverse genetic studies (attempted knockout) of PfRCC-PIP (PF3D7_0711500) failed to yield viable parasites, 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 lab, single method (failed KO), no conditional system to confirm essentiality rigorously\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0711500 (PfRCC-PIP) is a nuclear-localized protein in P. falciparum that acts as a dual anchoring scaffold, directly binding both the phosphatase PfPP1 (in vitro and in the parasite) and the kinase CDPK7 via its RCC1 motifs, thereby potentially coordinating phosphorylation/dephosphorylation processes; it appears to be essential for parasite viability based on failed knockout attempts.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0711500 is a nuclear protein of Plasmodium falciparum, identified by nuclear-fraction proteomics and confirmed with tagged transgenic lines [#0]. Named PfRCC-PIP, it functions as a dual anchoring scaffold: it directly binds the parasite Protein Phosphatase type-1 (PfPP1) both in vitro and in the parasite, and the region containing its RCC1 motifs also engages the parasite kinase CDPK7, positioning it to bridge a phosphatase and a kinase [#1]. Attempted knockout yielded no viable parasites, consistent with a role essential for asexual survival [#2]. Beyond these interaction and localization findings, the downstream substrates and the biological consequence of the PfPP1/CDPK7 anchoring have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Whether PF3D7_0711500 resides in a specific subcellular compartment was unknown; establishing nuclear localization provided the first functional context for this putative RCC1-motif protein.\",\n      \"evidence\": \"High-accuracy mass spectrometry of P. falciparum nuclear fractions with transgenic tagged-line validation\",\n      \"pmids\": [\"23181666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of nuclear localization not tested for this protein\",\n        \"No cell-cycle or chromatin association demonstrated\",\n        \"Interaction partners unidentified at this stage\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unknown what molecular partners PF3D7_0711500 engaged; direct binding to PfPP1 and to CDPK7 via its RCC1-motif region established it as a dual kinase/phosphatase anchoring scaffold (PfRCC-PIP).\",\n      \"evidence\": \"In vitro binding assay, co-immunoprecipitation from parasite lysate, and Xenopus oocyte PP1 regulatory assay\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Substrates dephosphorylated/phosphorylated within the complex not identified\",\n        \"Biological process coordinated by the anchoring not defined\",\n        \"Structural basis of RCC1-motif binding to CDPK7 not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the gene is required for parasite growth was untested; failure to recover knockout parasites indicated it is likely essential for survival.\",\n      \"evidence\": \"Reverse genetics / attempted gene knockout in P. falciparum\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single failed-KO approach without a conditional system to rigorously confirm essentiality\",\n        \"Stage-specific requirement not defined\",\n        \"No phenotype from controlled depletion\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The downstream substrates and the cellular process coordinated by the PfPP1/CDPK7 anchoring function of PF3D7_0711500 remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate of the anchored phosphatase/kinase identified\",\n        \"No conditional-depletion phenotype linking the scaffold to a specific pathway\",\n        \"No structural model of the complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019903\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"PfRCC-PIP–PfPP1 complex in the parasite [#1]\"],\n    \"partners\": [\"PfPP1 (Protein Phosphatase type-1) [#1]\", \"CDPK7 [#1]\"],\n    \"other_free_text\": [\n      \"Contains RCC1 motifs that mediate the interaction with CDPK7 [#1]\",\n      \"Attempted knockout produced no viable parasites, indicating likely essentiality [#2]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0711500","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 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_0711500","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1222100","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0110200","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}