{"gene":"PF3D7_0403100","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_0403100 (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 interaction assay and co-immunoprecipitation from parasite lysate","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal in vitro pull-down plus co-IP from parasite, single lab, two orthogonal methods","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PF3D7_0403100 (PfRCC-PIP) can interact with endogenous Xenopus PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating 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 / Weak — functional cell-based 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 PF3D7_0403100 (PfRCC-PIP) interacts with the parasite kinase PfCDPK7, identifying it as a kinase anchoring protein in addition to its role as a phosphatase-anchoring protein.","method":"Protein–protein interaction assay (in vitro binding with RCC1 domain fragment and PfCDPK7)","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown/interaction assay, single lab, single method, no mutagenesis or functional follow-up","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_0403100 (PfRCC-PIP), suggesting the gene is essential for parasite viability.","method":"Attempted gene knock-out by reverse genetics; no viable KO clones recovered","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — negative selection (failure to obtain KO) as essentiality evidence, single lab, single method, no conditional KO validation","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0403100 (PfRCC-PIP) functions as a dual kinase- and phosphatase-anchoring protein in P. falciparum: it directly binds and positively regulates PfPP1, and its RCC1 motif region recruits the kinase PfCDPK7, thereby providing a scaffold that coordinates phosphorylation/dephosphorylation processes; the gene appears essential for parasite viability."},"narrative":{"mechanistic_narrative":"PF3D7_0403100 (PfRCC-PIP) is a dual anchoring protein in Plasmodium falciparum that scaffolds phosphorylation and dephosphorylation activities. It directly binds Protein Phosphatase type-1 (PfPP1), forming a complex in the parasite where it acts as a major PfPP1 partner [PMID:30429842], and it positively regulates phosphatase activity, synergizing with suboptimal progesterone doses to promote oocyte maturation in a heterologous Xenopus assay [PMID:30429842]. Its RCC1-motif-containing region additionally engages the parasite kinase PfCDPK7, identifying it as a kinase-anchoring protein alongside its phosphatase-anchoring role [PMID:30429842]. Attempts to generate knock-out parasites failed, indicating the gene is essential for parasite viability [PMID:30429842]. Beyond these interactions and the essentiality inference, no further mechanistic detail — including in vivo substrates, structural basis of binding, or the physiological consequences of PfCDPK7 anchoring — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether PF3D7_0403100 physically associates with a phosphatase was unknown; establishing a direct PfPP1 interaction defined its identity as a phosphatase-binding scaffold in the parasite.","evidence":"In vitro interaction assay plus co-immunoprecipitation from parasite lysate","pmids":["30429842"],"confidence":"Medium","gaps":["Binding interface / PP1-docking motif on PF3D7_0403100 not mapped","Endogenous substrates of the PfPP1 complex not identified","Stoichiometry and other complex members not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether the interaction merely tethers or actively modulates PP1 was unknown; a heterologous functional assay showed PF3D7_0403100 activates PP1 to lower the progesterone threshold for oocyte maturation, establishing it as a positive regulator.","evidence":"Xenopus oocyte maturation assay with progesterone dose-response, using endogenous Xenopus PP1","pmids":["30429842"],"confidence":"Medium","gaps":["Regulatory effect shown in Xenopus, not demonstrated on PfPP1 in the parasite","Molecular mechanism of PP1 activation unresolved","Single method, single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether PF3D7_0403100 also engages a kinase was unknown; its RCC1-motif region was shown to bind PfCDPK7, extending its role to a dual kinase- and phosphatase-anchoring scaffold.","evidence":"In vitro binding assay between the RCC1-domain fragment and PfCDPK7","pmids":["30429842"],"confidence":"Low","gaps":["Single pulldown without mutagenesis or reciprocal validation","Functional consequence of CDPK7 anchoring not tested","Interaction not confirmed in the parasite in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether the gene is required for parasite survival was unknown; failure to recover knock-out clones suggested essentiality, framing PF3D7_0403100 as a candidate node in essential signaling.","evidence":"Attempted reverse-genetic gene knock-out; no viable clones recovered","pmids":["30429842"],"confidence":"Low","gaps":["Essentiality inferred from failed KO, not confirmed by conditional knockdown/knockout","Stage-specific requirement not established","No demonstration that essentiality depends on PP1 or CDPK7 binding"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in-parasite substrates coordinated by this kinase/phosphatase scaffold and the physiological process it controls remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional-knockdown phenotype defining the cellular process affected","No structural or mutational mapping of the PP1- and CDPK7-binding regions","No identification of substrates dephosphorylated/phosphorylated via the scaffold"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfPP1-containing complex in P. falciparum"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE-1)","PFCDPK7","XENOPUS PP1 (HETEROLOGOUS)"],"other_free_text":["Essential for P. falciparum viability inferred from failed knock-out (Low confidence)","Contains an RCC1-motif-containing region that mediates PfCDPK7 binding","Acts as a dual kinase- and phosphatase-anchoring scaffold"]}},"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":1030,"usd":0.012592,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5730,"output_tokens":2162,"usd":0.04135,"stage2_stop_reason":"end_turn"},"total_usd":0.053942,"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_0403100 (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 interaction assay and co-immunoprecipitation from parasite lysate\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal in vitro pull-down plus co-IP from 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_0403100 (PfRCC-PIP) can interact with endogenous Xenopus PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating 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 / Weak — functional cell-based 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 PF3D7_0403100 (PfRCC-PIP) interacts with the parasite kinase PfCDPK7, identifying it as a kinase anchoring protein in addition to its role as a phosphatase-anchoring protein.\",\n      \"method\": \"Protein–protein interaction assay (in vitro binding with RCC1 domain fragment and PfCDPK7)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown/interaction assay, single lab, single method, no mutagenesis or functional follow-up\",\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_0403100 (PfRCC-PIP), suggesting the gene is essential for parasite viability.\",\n      \"method\": \"Attempted gene knock-out by reverse genetics; no viable KO clones recovered\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — negative selection (failure to obtain KO) as essentiality evidence, single lab, single method, no conditional KO validation\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0403100 (PfRCC-PIP) functions as a dual kinase- and phosphatase-anchoring protein in P. falciparum: it directly binds and positively regulates PfPP1, and its RCC1 motif region recruits the kinase PfCDPK7, thereby providing a scaffold that coordinates phosphorylation/dephosphorylation processes; the gene appears essential for parasite viability.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0403100 (PfRCC-PIP) is a dual anchoring protein in Plasmodium falciparum that scaffolds phosphorylation and dephosphorylation activities. It directly binds Protein Phosphatase type-1 (PfPP1), forming a complex in the parasite where it acts as a major PfPP1 partner [#0], and it positively regulates phosphatase activity, synergizing with suboptimal progesterone doses to promote oocyte maturation in a heterologous Xenopus assay [#1]. Its RCC1-motif-containing region additionally engages the parasite kinase PfCDPK7, identifying it as a kinase-anchoring protein alongside its phosphatase-anchoring role [#2]. Attempts to generate knock-out parasites failed, indicating the gene is essential for parasite viability [#3]. Beyond these interactions and the essentiality inference, no further mechanistic detail — including in vivo substrates, structural basis of binding, or the physiological consequences of PfCDPK7 anchoring — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether PF3D7_0403100 physically associates with a phosphatase was unknown; establishing a direct PfPP1 interaction defined its identity as a phosphatase-binding scaffold in the parasite.\",\n      \"evidence\": \"In vitro interaction assay plus co-immunoprecipitation from parasite lysate\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding interface / PP1-docking motif on PF3D7_0403100 not mapped\",\n        \"Endogenous substrates of the PfPP1 complex not identified\",\n        \"Stoichiometry and other complex members not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the interaction merely tethers or actively modulates PP1 was unknown; a heterologous functional assay showed PF3D7_0403100 activates PP1 to lower the progesterone threshold for oocyte maturation, establishing it as a positive regulator.\",\n      \"evidence\": \"Xenopus oocyte maturation assay with progesterone dose-response, using endogenous Xenopus PP1\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Regulatory effect shown in Xenopus, not demonstrated on PfPP1 in the parasite\",\n        \"Molecular mechanism of PP1 activation unresolved\",\n        \"Single method, single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether PF3D7_0403100 also engages a kinase was unknown; its RCC1-motif region was shown to bind PfCDPK7, extending its role to a dual kinase- and phosphatase-anchoring scaffold.\",\n      \"evidence\": \"In vitro binding assay between the RCC1-domain fragment and PfCDPK7\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single pulldown without mutagenesis or reciprocal validation\",\n        \"Functional consequence of CDPK7 anchoring not tested\",\n        \"Interaction not confirmed in the parasite in vivo\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the gene is required for parasite survival was unknown; failure to recover knock-out clones suggested essentiality, framing PF3D7_0403100 as a candidate node in essential signaling.\",\n      \"evidence\": \"Attempted reverse-genetic gene knock-out; no viable clones recovered\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Essentiality inferred from failed KO, not confirmed by conditional knockdown/knockout\",\n        \"Stage-specific requirement not established\",\n        \"No demonstration that essentiality depends on PP1 or CDPK7 binding\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in-parasite substrates coordinated by this kinase/phosphatase scaffold and the physiological process it controls remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No conditional-knockdown phenotype defining the cellular process affected\",\n        \"No structural or mutational mapping of the PP1- and CDPK7-binding regions\",\n        \"No identification of substrates dephosphorylated/phosphorylated via the scaffold\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004864\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0019212\", \"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      {\"term_id\": \"GO:0006468\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"PfPP1-containing complex in P. falciparum\"\n    ],\n    \"partners\": [\n      \"PfPP1 (Protein Phosphatase type-1)\",\n      \"PfCDPK7\",\n      \"Xenopus PP1 (heterologous)\"\n    ],\n    \"other_free_text\": [\n      \"Essential for P. falciparum viability inferred from failed knock-out (Low confidence)\",\n      \"Contains an RCC1-motif-containing region that mediates PfCDPK7 binding\",\n      \"Acts as a dual kinase- and phosphatase-anchoring scaffold\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0403100","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_0403100","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1000700","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0300900","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}