{"gene":"PF3D7_0930200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2006,"finding":"LRR8/PF3D7_0930200 is the P. falciparum Sds22 orthologue designated PfLRR1; GST pull-down assay showed that PfLRR1 directly interacts with PfPP1, the PfLRR1–PfPP1 complex is present in native parasite extracts, and PfLRR1 inhibits PfPP1 phosphatase activity in vitro.","method":"GST pull-down assay, co-immunoprecipitation from parasite extracts, in vitro phosphatase activity assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pull-down plus native complex detection plus enzymatic inhibition assay, single lab, multiple orthogonal methods","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"When expressed in Xenopus oocytes, PfLRR1 (LRR8/PF3D7_0930200) interacted with endogenous Xenopus PP1 and promoted progression past the G2/M checkpoint, inducing germinal vesicle breakdown (GVBD), consistent with inhibition of PP1 driving cell-cycle progression.","method":"Xenopus oocyte microinjection/expression, GVBD readout as cell-cycle checkpoint assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cell-cycle assay in heterologous system with mechanistic readout; single lab, corroborated by okadaic acid and anti-PP1 antibody controls","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Census of the P. falciparum genome identified 14 LRR-containing proteins (PfLRR1–PfLRR14); cDNA cloning and sequencing confirmed that PfLRR1 (LRR8/PF3D7_0930200) contains 4–10 LRR motifs, and RT-qPCR showed it is highly transcribed in late intraerythrocytic stages (late trophozoites and schizonts).","method":"Genomic analysis, cDNA cloning and sequencing, real-time quantitative PCR across intraerythrocytic stages","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional expression profiling with no functional mechanistic follow-up in this paper","pmids":["17689674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"LRR8 (PF3D7_0930200), the P. falciparum orthologue of the conserved PP1 regulator Sds22, directly binds to and inhibits protein phosphatase 1 (PfPP1) — as demonstrated by pull-down, native complex co-immunoprecipitation, and in vitro phosphatase assays — and when expressed heterologously can override the G2/M cell-cycle checkpoint, suggesting that LRR8 regulates the parasite cell cycle by modulating PP1 activity; the gene is preferentially transcribed in late intraerythrocytic stages."},"narrative":{"mechanistic_narrative":"LRR8 (PF3D7_0930200) is the P. falciparum orthologue of the conserved PP1 regulator Sds22, functioning as a leucine-rich repeat regulator of protein phosphatase 1 (PfPP1) that couples phosphatase activity to parasite cell-cycle control [PMID:16629662]. In P. falciparum, LRR8 directly binds PfPP1, exists in complex with PfPP1 in native parasite extracts, and inhibits PfPP1 phosphatase activity in vitro [PMID:16629662]. Consistent with this inhibitory role driving cell-cycle progression, heterologous expression of LRR8 in Xenopus oocytes engaged endogenous PP1 and promoted passage through the G2/M checkpoint, inducing germinal vesicle breakdown [PMID:16629662]. The gene is preferentially transcribed in late intraerythrocytic stages (late trophozoites and schizonts) [PMID:17689674], the developmental window associated with schizogony. Beyond its role as a direct PfPP1-binding inhibitor and its stage-restricted expression, no further mechanistic detail — including in-parasite loss-of-function phenotype or structural basis of the interaction — has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Established that LRR8 is a direct physical and functional regulator of PfPP1, answering whether the Plasmodium Sds22 orthologue acts on the parasite phosphatase and in which direction.","evidence":"GST pull-down, co-immunoprecipitation of the native complex from parasite extracts, and in vitro phosphatase activity assay in P. falciparum","pmids":["16629662"],"confidence":"Medium","gaps":["Structural basis of the LRR8-PfPP1 interaction is undefined","In-parasite loss-of-function phenotype of LRR8 not tested","Whether inhibition is complete or partial/context-dependent in vivo unaddressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Demonstrated a cell-cycle consequence of LRR8-mediated PP1 inhibition, linking the phosphatase interaction to G2/M checkpoint control.","evidence":"Xenopus oocyte expression of PfLRR1 with GVBD readout, corroborated by okadaic acid and anti-PP1 antibody controls","pmids":["16629662"],"confidence":"Medium","gaps":["Cell-cycle role shown only in heterologous Xenopus system, not in the parasite","Downstream PfPP1 substrates governing the parasite cell cycle not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Placed LRR8 within the parasite's LRR protein family and defined its developmental expression window, indicating when its PfPP1-regulatory activity is deployed.","evidence":"Genomic census of 14 LRR proteins, cDNA cloning/sequencing, and RT-qPCR across intraerythrocytic stages in P. falciparum","pmids":["17689674"],"confidence":"Low","gaps":["Transcriptional profiling only, with no functional follow-up in this study","Protein-level abundance and localization not measured","Functional distinction of LRR8 from other family members not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether LRR8 is essential in the blood-stage parasite and which PfPP1-dependent substrates and cell-cycle transitions it controls in vivo remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or conditional knockdown of LRR8 reported in the corpus","No identification of physiological PfPP1 substrates modulated by LRR8","No structural model of the LRR8-PfPP1 complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["LRR8 (PfLRR1)-PfPP1 complex"],"partners":["PFPP1 (PROTEIN PHOSPHATASE 1)","ENDOGENOUS XENOPUS PP1 (HETEROLOGOUS SYSTEM)"],"other_free_text":["P. falciparum Sds22 orthologue (designated PfLRR1)","Leucine-rich repeat protein containing 4-10 LRR motifs","Preferentially transcribed in late intraerythrocytic stages (late trophozoites and schizonts)","Member of a 14-protein P. falciparum LRR family (PfLRR1-PfLRR14)"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16629662","id":"PMC_16629662","title":"Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine-rich repeat protein of the human malaria parasite Plasmodium falciparum.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16629662","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17689674","id":"PMC_17689674","title":"Census, molecular characterization and developmental expression of Leucine-Rich-Repeat proteins in Plasmodium falciparum.","date":"2007","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17689674","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35920043","id":"PMC_35920043","title":"Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.","date":"2022","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/35920043","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42294623","id":"PMC_42294623","title":"Plasmodium falciparum leucine-rich repeat 5 disruption alters the transcription progression during asexual and sexual stage development.","date":"2026","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/42294623","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10056,"output_tokens":1494,"usd":0.041387,"retried_sync":true},"stage2":{"model":"claude-opus-4-8","input_tokens":5723,"output_tokens":1990,"usd":0.039183,"stage2_stop_reason":"end_turn"},"total_usd":0.08057,"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\": 2006,\n      \"finding\": \"LRR8/PF3D7_0930200 is the P. falciparum Sds22 orthologue designated PfLRR1; GST pull-down assay showed that PfLRR1 directly interacts with PfPP1, the PfLRR1–PfPP1 complex is present in native parasite extracts, and PfLRR1 inhibits PfPP1 phosphatase activity in vitro.\",\n      \"method\": \"GST pull-down assay, co-immunoprecipitation from parasite extracts, in vitro phosphatase activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pull-down plus native complex detection plus enzymatic inhibition assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"When expressed in Xenopus oocytes, PfLRR1 (LRR8/PF3D7_0930200) interacted with endogenous Xenopus PP1 and promoted progression past the G2/M checkpoint, inducing germinal vesicle breakdown (GVBD), consistent with inhibition of PP1 driving cell-cycle progression.\",\n      \"method\": \"Xenopus oocyte microinjection/expression, GVBD readout as cell-cycle checkpoint assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cell-cycle assay in heterologous system with mechanistic readout; single lab, corroborated by okadaic acid and anti-PP1 antibody controls\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Census of the P. falciparum genome identified 14 LRR-containing proteins (PfLRR1–PfLRR14); cDNA cloning and sequencing confirmed that PfLRR1 (LRR8/PF3D7_0930200) contains 4–10 LRR motifs, and RT-qPCR showed it is highly transcribed in late intraerythrocytic stages (late trophozoites and schizonts).\",\n      \"method\": \"Genomic analysis, cDNA cloning and sequencing, real-time quantitative PCR across intraerythrocytic stages\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional expression profiling with no functional mechanistic follow-up in this paper\",\n      \"pmids\": [\"17689674\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"LRR8 (PF3D7_0930200), the P. falciparum orthologue of the conserved PP1 regulator Sds22, directly binds to and inhibits protein phosphatase 1 (PfPP1) — as demonstrated by pull-down, native complex co-immunoprecipitation, and in vitro phosphatase assays — and when expressed heterologously can override the G2/M cell-cycle checkpoint, suggesting that LRR8 regulates the parasite cell cycle by modulating PP1 activity; the gene is preferentially transcribed in late intraerythrocytic stages.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"LRR8 (PF3D7_0930200) is the P. falciparum orthologue of the conserved PP1 regulator Sds22, functioning as a leucine-rich repeat regulator of protein phosphatase 1 (PfPP1) that couples phosphatase activity to parasite cell-cycle control [#0]. In P. falciparum, LRR8 directly binds PfPP1, exists in complex with PfPP1 in native parasite extracts, and inhibits PfPP1 phosphatase activity in vitro [#0]. Consistent with this inhibitory role driving cell-cycle progression, heterologous expression of LRR8 in Xenopus oocytes engaged endogenous PP1 and promoted passage through the G2/M checkpoint, inducing germinal vesicle breakdown [#1]. The gene is preferentially transcribed in late intraerythrocytic stages (late trophozoites and schizonts) [#2], the developmental window associated with schizogony. Beyond its role as a direct PfPP1-binding inhibitor and its stage-restricted expression, no further mechanistic detail — including in-parasite loss-of-function phenotype or structural basis of the interaction — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that LRR8 is a direct physical and functional regulator of PfPP1, answering whether the Plasmodium Sds22 orthologue acts on the parasite phosphatase and in which direction.\",\n      \"evidence\": \"GST pull-down, co-immunoprecipitation of the native complex from parasite extracts, and in vitro phosphatase activity assay in P. falciparum\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of the LRR8-PfPP1 interaction is undefined\",\n        \"In-parasite loss-of-function phenotype of LRR8 not tested\",\n        \"Whether inhibition is complete or partial/context-dependent in vivo unaddressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated a cell-cycle consequence of LRR8-mediated PP1 inhibition, linking the phosphatase interaction to G2/M checkpoint control.\",\n      \"evidence\": \"Xenopus oocyte expression of PfLRR1 with GVBD readout, corroborated by okadaic acid and anti-PP1 antibody controls\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cell-cycle role shown only in heterologous Xenopus system, not in the parasite\",\n        \"Downstream PfPP1 substrates governing the parasite cell cycle not identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Placed LRR8 within the parasite's LRR protein family and defined its developmental expression window, indicating when its PfPP1-regulatory activity is deployed.\",\n      \"evidence\": \"Genomic census of 14 LRR proteins, cDNA cloning/sequencing, and RT-qPCR across intraerythrocytic stages in P. falciparum\",\n      \"pmids\": [\"17689674\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcriptional profiling only, with no functional follow-up in this study\",\n        \"Protein-level abundance and localization not measured\",\n        \"Functional distinction of LRR8 from other family members not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether LRR8 is essential in the blood-stage parasite and which PfPP1-dependent substrates and cell-cycle transitions it controls in vivo remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout or conditional knockdown of LRR8 reported in the corpus\",\n        \"No identification of physiological PfPP1 substrates modulated by LRR8\",\n        \"No structural model of the LRR8-PfPP1 complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004865\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008157\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007346\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0044819\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"LRR8 (PfLRR1)-PfPP1 complex\"\n    ],\n    \"partners\": [\n      \"PfPP1 (protein phosphatase 1)\",\n      \"endogenous Xenopus PP1 (heterologous system)\"\n    ],\n    \"other_free_text\": [\n      \"P. falciparum Sds22 orthologue (designated PfLRR1)\",\n      \"Leucine-rich repeat protein containing 4-10 LRR motifs\",\n      \"Preferentially transcribed in late intraerythrocytic stages (late trophozoites and schizonts)\",\n      \"Member of a 14-protein P. falciparum LRR family (PfLRR1-PfLRR14)\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_0930200","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_1032800, PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0930200","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0830900","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0728700","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"LRR8","evaluation":null}