{"gene":"PF3D7_1143500","run_date":"2026-09-08T14:19:05","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_1143500 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and is present in complex with PfPP1 in the parasite, acting 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 — reciprocal in vitro and in-parasite co-IP data from a single lab, two orthogonal methods","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfRCC-PIP (PF3D7_1143500), when expressed in Xenopus oocytes, interacts with endogenous 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","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional heterologous system (Xenopus oocyte) with clear phenotypic 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_1143500 interacts with the parasite kinase CDPK7, indicating that the protein can also function as a kinase anchoring protein.","method":"In vitro protein interaction assay (domain mapping)","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown/binding assay with a defined protein region, single lab, single method","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Reverse genetic studies (attempted knock-out) yielded no viable knock-out parasites, suggesting PF3D7_1143500 is essential for P. falciparum viability.","method":"Reverse genetics / attempted gene knock-out","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — negative selection result from a single attempted KO experiment, single lab; essentiality inferred but not rigorously confirmed with complementation","pmids":["30429842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1143500 (PfRCC-PIP) functions as a dual kinase- and phosphatase-anchoring scaffold in P. falciparum: its RCC1 motif-containing region binds the kinase CDPK7, while its direct interaction with PfPP1 (demonstrated in vitro and in the parasite) modulates PP1 activity, and the protein appears essential for parasite viability."},"narrative":{"mechanistic_narrative":"PF3D7_1143500 (PfRCC-PIP) is an RCC1 motif-containing scaffold protein of Plasmodium falciparum that acts as a regulatory anchoring partner for the parasite Protein Phosphatase type-1 (PfPP1). It directly binds PfPP1 in vitro and forms a complex with PfPP1 in the parasite, ranking as a major PfPP1 interactor [PMID:30429842], and in a heterologous Xenopus oocyte system it engages endogenous PP1 and synergizes with suboptimal progesterone to promote oocyte maturation, indicating a positive regulatory effect on PP1 activity [PMID:30429842]. Its RCC1 motif-containing region also binds the parasite kinase CDPK7, consistent with a role as a dual kinase- and phosphatase-anchoring scaffold [PMID:30429842], and attempted knock-out yielded no viable parasites, indicating the protein is required for blood-stage viability [PMID:30429842]. Beyond these interaction and essentiality observations, no further mechanistic detail — substrate specificity, structural basis of binding, or in-parasite phosphoregulatory targets — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing whether PF3D7_1143500 physically partners a signaling enzyme addressed whether this RCC1-motif protein functions in phosphoregulation; it was shown to be a major direct binding partner of PfPP1 both in vitro and in the parasite.","evidence":"In vitro binding assay and co-immunoprecipitation from P. falciparum lysate","pmids":["30429842"],"confidence":"Medium","gaps":["The structural basis and interaction interface with PfPP1 are not defined","Whether the interaction is constitutive or cell-cycle/stage-regulated is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To determine whether the PfPP1 interaction is functional rather than merely physical, the protein was tested in a heterologous system, showing it activates PP1-dependent oocyte maturation and thereby acts as a positive regulator of PP1 activity.","evidence":"Xenopus oocyte functional maturation assay with suboptimal progesterone","pmids":["30429842"],"confidence":"Medium","gaps":["Regulatory effect on PfPP1 activity was inferred from a heterologous system, not measured on the parasite enzyme","The in-parasite substrates and dephosphorylation events controlled remain unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Mapping partner binding to the RCC1 motif-containing region tested whether the scaffold engages more than one enzyme, revealing an interaction with the kinase CDPK7 and suggesting a dual kinase/phosphatase anchoring role.","evidence":"In vitro protein interaction assay with domain mapping","pmids":["30429842"],"confidence":"Low","gaps":["Single pulldown/binding assay without reciprocal or in-parasite validation","Functional consequence of CDPK7 anchoring is untested","Whether PfPP1 and CDPK7 binding are simultaneous or mutually exclusive is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Attempted gene disruption addressed whether the protein is required for parasite survival, with failure to recover knock-outs indicating essentiality for blood-stage viability.","evidence":"Reverse genetics / attempted gene knock-out in P. falciparum","pmids":["30429842"],"confidence":"Low","gaps":["Essentiality inferred from a single failed KO attempt without conditional or complementation confirmation","The essential molecular function driving viability is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in-parasite phosphoregulatory function of PF3D7_1143500 — its physiological PfPP1 substrates, the structural basis of PP1/CDPK7 binding, and its role across the parasite life cycle — remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate of the PfRCC-PIP/PfPP1 complex identified","No structural model of the interactions","Essentiality not confirmed by conditional depletion"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfRCC-PIP–PfPP1 complex"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE-1)","CDPK7","ENDOGENOUS PP1 (HETEROLOGOUS XENOPUS)"],"other_free_text":["RCC1 motif-containing region mediates the interaction with the kinase CDPK7 [#2]","Attempted knock-out failed, indicating essentiality for P. falciparum viability [#3]","Acts as a positive regulator of PP1 activity in a Xenopus oocyte maturation assay [#1]"]}},"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":977,"usd":0.012195,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5654,"output_tokens":2109,"usd":0.040497,"stage2_stop_reason":"end_turn"},"total_usd":0.052692,"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_1143500 (PfRCC-PIP) directly interacts with PfPP1 (Protein Phosphatase type-1) in vitro and is present in complex with PfPP1 in the parasite, acting 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 — reciprocal in vitro and in-parasite co-IP data from a 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\": \"PfRCC-PIP (PF3D7_1143500), when expressed in Xenopus oocytes, interacts with endogenous 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\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional heterologous system (Xenopus oocyte) with clear phenotypic 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_1143500 interacts with the parasite kinase CDPK7, indicating that the protein can also function as a kinase anchoring protein.\",\n      \"method\": \"In vitro protein interaction assay (domain mapping)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown/binding assay with a defined protein region, single lab, single method\",\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) yielded no viable knock-out parasites, suggesting PF3D7_1143500 is essential for P. falciparum viability.\",\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 from a single attempted KO experiment, single lab; essentiality inferred but not rigorously confirmed with complementation\",\n      \"pmids\": [\"30429842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1143500 (PfRCC-PIP) functions as a dual kinase- and phosphatase-anchoring scaffold in P. falciparum: its RCC1 motif-containing region binds the kinase CDPK7, while its direct interaction with PfPP1 (demonstrated in vitro and in the parasite) modulates PP1 activity, and the protein appears essential for parasite viability.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1143500 (PfRCC-PIP) is an RCC1 motif-containing scaffold protein of Plasmodium falciparum that acts as a regulatory anchoring partner for the parasite Protein Phosphatase type-1 (PfPP1). It directly binds PfPP1 in vitro and forms a complex with PfPP1 in the parasite, ranking as a major PfPP1 interactor [#0], and in a heterologous Xenopus oocyte system it engages endogenous PP1 and synergizes with suboptimal progesterone to promote oocyte maturation, indicating a positive regulatory effect on PP1 activity [#1]. Its RCC1 motif-containing region also binds the parasite kinase CDPK7, consistent with a role as a dual kinase- and phosphatase-anchoring scaffold [#2], and attempted knock-out yielded no viable parasites, indicating the protein is required for blood-stage viability [#3]. Beyond these interaction and essentiality observations, no further mechanistic detail — substrate specificity, structural basis of binding, or in-parasite phosphoregulatory targets — has been characterized in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing whether PF3D7_1143500 physically partners a signaling enzyme addressed whether this RCC1-motif protein functions in phosphoregulation; it was shown to be a major direct binding partner of PfPP1 both in vitro and in the parasite.\",\n      \"evidence\": \"In vitro binding assay and co-immunoprecipitation from P. falciparum lysate\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The structural basis and interaction interface with PfPP1 are not defined\",\n        \"Whether the interaction is constitutive or cell-cycle/stage-regulated is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To determine whether the PfPP1 interaction is functional rather than merely physical, the protein was tested in a heterologous system, showing it activates PP1-dependent oocyte maturation and thereby acts as a positive regulator of PP1 activity.\",\n      \"evidence\": \"Xenopus oocyte functional maturation assay with suboptimal progesterone\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Regulatory effect on PfPP1 activity was inferred from a heterologous system, not measured on the parasite enzyme\",\n        \"The in-parasite substrates and dephosphorylation events controlled remain unidentified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapping partner binding to the RCC1 motif-containing region tested whether the scaffold engages more than one enzyme, revealing an interaction with the kinase CDPK7 and suggesting a dual kinase/phosphatase anchoring role.\",\n      \"evidence\": \"In vitro protein interaction assay with domain mapping\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single pulldown/binding assay without reciprocal or in-parasite validation\",\n        \"Functional consequence of CDPK7 anchoring is untested\",\n        \"Whether PfPP1 and CDPK7 binding are simultaneous or mutually exclusive is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Attempted gene disruption addressed whether the protein is required for parasite survival, with failure to recover knock-outs indicating essentiality for blood-stage viability.\",\n      \"evidence\": \"Reverse genetics / attempted gene knock-out in P. falciparum\",\n      \"pmids\": [\"30429842\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Essentiality inferred from a single failed KO attempt without conditional or complementation confirmation\",\n        \"The essential molecular function driving viability is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in-parasite phosphoregulatory function of PF3D7_1143500 — its physiological PfPP1 substrates, the structural basis of PP1/CDPK7 binding, and its role across the parasite life cycle — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate of the PfRCC-PIP/PfPP1 complex identified\",\n        \"No structural model of the interactions\",\n        \"Essentiality not confirmed by conditional depletion\"\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:0019903\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019894\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"PfRCC-PIP–PfPP1 complex\"],\n    \"partners\": [\"PfPP1 (Protein Phosphatase type-1)\", \"CDPK7\", \"endogenous PP1 (heterologous Xenopus)\"],\n    \"other_free_text\": [\n      \"RCC1 motif-containing region mediates the interaction with the kinase CDPK7 [#2]\",\n      \"Attempted knock-out failed, indicating essentiality for P. falciparum viability [#3]\",\n      \"Acts as a positive regulator of PP1 activity in a Xenopus oocyte maturation assay [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1143500","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_1143500","name":null,"product":"regulator of chromosome condensation, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0905500","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0941400","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}