{"gene":"PF3D7_1123200","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2006,"finding":"LRR11 (PfLRR1) gene product physically interacts with PfPP1 (protein phosphatase type 1), as demonstrated by GST pull-down assay; the LRR11–PfPP1 complex is also present in native parasite extracts, and LRR11 inhibits PfPP1 phosphatase activity in vitro.","method":"GST pull-down assay, parasite extract co-immunoprecipitation, in vitro phosphatase activity assay","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal pull-down plus in vitro activity assay plus native complex detection, single lab but multiple orthogonal methods","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"LRR11 (PfLRR1) expressed in Xenopus oocytes interacts with endogenous Xenopus PP1 and promotes G2/M progression (germinal vesicle breakdown, GVBD), mimicking the effect of PP1 inhibition by okadaic acid or anti-PP1 antibodies, indicating that LRR11 can override the G2/M cell cycle checkpoint through PP1 regulation.","method":"Xenopus oocyte functional assay, GVBD scoring, comparison with okadaic acid and anti-PP1 antibody controls","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional heterologous system with multiple controls, single lab","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"LRR11 (designated PfLRR1 in the paper's census) is one of 14 LRR-containing proteins identified in P. falciparum; molecular cloning and cDNA sequencing confirmed it contains 4–10 LRR motifs, and real-time quantitative PCR showed it is highly transcribed in late intraerythrocytic stages (late trophozoites and schizonts).","method":"Genome-wide computational identification, molecular cloning, cDNA sequencing, real-time quantitative PCR across intraerythrocytic life-cycle stages","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — molecular characterisation by cloning/sequencing plus RT-qPCR stage profiling, single lab","pmids":["17689674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"The P. berghei orthologue of LRR11 (PbLRR1) forms a complex with PbPP1 in both asexual and sexual stages and inhibits PbPP1 phosphatase activity; genetic depletion of PbLRR1 adversely affects oocyst development in mosquitoes.","method":"Co-immunoprecipitation (complex detection in parasite extracts), in vitro phosphatase activity assay, conditional genetic depletion with oocyst development quantification","journal":"Open biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal complex detection, in vitro activity assay, and loss-of-function phenotype with defined developmental readout, single lab but multiple orthogonal methods","pmids":["35920043"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"In P. berghei, Inhibitor 3 (I3) — a direct PbPP1 interactant — was found in the PbLRR1 interactome and was drastically hypophosphorylated in PbLRR1-depleted parasites, indicating that the PP1–LRR1 complex controls the phosphorylation status of I3, placing LRR11 (PbLRR1) upstream of I3 phosphorylation in the PP1 regulatory network.","method":"LRR1 interactome mass spectrometry, phospho-proteomics on PbLRR1-depleted parasites","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interactome MS combined with phospho-proteomics, single lab, two orthogonal methods","pmids":["35920043"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"LRR11 (PfLRR1/PbLRR1) is a leucine-rich repeat protein that physically binds protein phosphatase type 1 (PP1) in both P. falciparum and P. berghei, inhibits PP1 catalytic activity, promotes cell cycle G2/M progression via PP1 suppression, and in P. berghei controls the phosphorylation status of PP1 regulator Inhibitor 3 (I3) to support efficient oocyst development in the mosquito."},"narrative":{"mechanistic_narrative":"LRR11 (PF3D7_1123200; PfLRR1) is a leucine-rich repeat protein of Plasmodium that functions as a regulator of protein phosphatase type 1 (PP1), coupling PP1 activity to cell-cycle progression and parasite development [PMID:16629662, PMID:35920043]. In P. falciparum, LRR11 physically binds PfPP1 both in vitro and as a native complex in parasite extracts, and inhibits PfPP1 catalytic activity [PMID:16629662]; it is one of 14 LRR-containing proteins in the parasite and is transcribed predominantly in late intraerythrocytic stages (late trophozoites and schizonts) [PMID:17689674]. When expressed heterologously in Xenopus oocytes, LRR11 engages endogenous PP1 and drives G2/M progression, phenocopying PP1 inhibition and indicating that its suppression of PP1 can override the G2/M checkpoint [PMID:16629662]. The P. berghei orthologue (PbLRR1) similarly complexes with and inhibits PbPP1 across asexual and sexual stages, and its depletion controls the phosphorylation status of the PP1 regulator Inhibitor 3 (I3) and impairs oocyst development in the mosquito, establishing LRR11 as a physiologically required node in the PP1 regulatory network [PMID:35920043]. Beyond its role as a PP1-binding regulator, no additional catalytic or structural mechanism for LRR11 has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing that LRR11 is not merely an LRR protein but a direct partner and inhibitor of PP1 defined its core biochemical function.","evidence":"GST pull-down, native parasite extract co-IP, and in vitro phosphatase assay in P. falciparum","pmids":["16629662"],"confidence":"High","gaps":["Structural basis of the LRR11–PfPP1 interaction not resolved","The PP1 residue or domain contacted by LRR11 not mapped","Whether inhibition is competitive with substrate or regulatory subunits unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"A heterologous Xenopus oocyte system linked LRR11's PP1 inhibition to a defined cell-cycle output, showing it can override the G2/M checkpoint.","evidence":"Xenopus oocyte GVBD assay with okadaic acid and anti-PP1 antibody controls","pmids":["16629662"],"confidence":"Medium","gaps":["G2/M-promoting role not directly demonstrated in the parasite cell cycle","Downstream cell-cycle effectors of PP1 in Plasmodium not identified","Heterologous system may not recapitulate parasite regulatory context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Cataloguing LRR11 among the parasite's LRR proteins and profiling its stage-specific transcription placed its expression at the late intraerythrocytic stages relevant to schizogony.","evidence":"Genome-wide identification, cloning/cDNA sequencing, and RT-qPCR stage profiling in P. falciparum","pmids":["17689674"],"confidence":"Medium","gaps":["Protein-level expression timing not established","Functional consequence of late-stage enrichment not tested","LRR motif contribution to PP1 binding not dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Genetic depletion in P. berghei moved LRR11 from an in vitro PP1 inhibitor to an in vivo developmental requirement, and phospho-proteomics placed it upstream of Inhibitor 3 phosphorylation.","evidence":"Co-IP, in vitro phosphatase assay, conditional depletion with oocyst quantification, interactome MS and phospho-proteomics in P. berghei","pmids":["35920043"],"confidence":"High","gaps":["Mechanism by which the PP1–LRR1 complex sets I3 phosphorylation not resolved","Whether I3 hypophosphorylation causes the oocyst defect not established","Asexual-stage essentiality of the orthologue not quantified in this readout"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How LRR11 integrates PP1 inhibition, I3 phosphorylation control, and cell-cycle/developmental timing into a single regulatory mechanism remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of LRR11 alone or bound to PP1","Direct in-parasite demonstration of G2/M control in P. falciparum absent","Causal chain from LRR11 loss to I3 hypophosphorylation to oocyst failure not established"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["LRR11–PfPP1 complex (P. falciparum)","PbLRR1–PbPP1 complex (P. berghei)"],"partners":["PFPP1 / PBPP1 (PROTEIN PHOSPHATASE TYPE 1)","INHIBITOR 3 (I3) — COMPONENT OF THE PBLRR1 INTERACTOME (P. BERGHEI)"],"other_free_text":["One of 14 LRR-containing proteins in P. falciparum, containing 4–10 LRR motifs [#2].","Transcribed predominantly in late intraerythrocytic stages (late trophozoites and schizonts) [#2].","Genetic depletion of the P. berghei orthologue impairs oocyst development in the mosquito [#3]."]}},"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":34,"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":"16714563","id":"PMC_16714563","title":"Identification of a novel antigen of Schistosoma mansoni shared with Plasmodium falciparum and evaluation of different cross-reactive antibody subclasses induced by human schistosomiasis and malaria.","date":"2006","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/16714563","citation_count":29,"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":7,"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":5,"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":4702,"output_tokens":1504,"usd":0.018333,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6415,"output_tokens":2333,"usd":0.0452,"stage2_stop_reason":"end_turn"},"total_usd":0.063533,"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\": \"LRR11 (PfLRR1) gene product physically interacts with PfPP1 (protein phosphatase type 1), as demonstrated by GST pull-down assay; the LRR11–PfPP1 complex is also present in native parasite extracts, and LRR11 inhibits PfPP1 phosphatase activity in vitro.\",\n      \"method\": \"GST pull-down assay, parasite extract co-immunoprecipitation, in vitro phosphatase activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pull-down plus in vitro activity assay plus native complex detection, single lab but 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\": \"LRR11 (PfLRR1) expressed in Xenopus oocytes interacts with endogenous Xenopus PP1 and promotes G2/M progression (germinal vesicle breakdown, GVBD), mimicking the effect of PP1 inhibition by okadaic acid or anti-PP1 antibodies, indicating that LRR11 can override the G2/M cell cycle checkpoint through PP1 regulation.\",\n      \"method\": \"Xenopus oocyte functional assay, GVBD scoring, comparison with okadaic acid and anti-PP1 antibody controls\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional heterologous system with multiple controls, single lab\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"LRR11 (designated PfLRR1 in the paper's census) is one of 14 LRR-containing proteins identified in P. falciparum; molecular cloning and cDNA sequencing confirmed it contains 4–10 LRR motifs, and real-time quantitative PCR showed it is highly transcribed in late intraerythrocytic stages (late trophozoites and schizonts).\",\n      \"method\": \"Genome-wide computational identification, molecular cloning, cDNA sequencing, real-time quantitative PCR across intraerythrocytic life-cycle stages\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — molecular characterisation by cloning/sequencing plus RT-qPCR stage profiling, single lab\",\n      \"pmids\": [\"17689674\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The P. berghei orthologue of LRR11 (PbLRR1) forms a complex with PbPP1 in both asexual and sexual stages and inhibits PbPP1 phosphatase activity; genetic depletion of PbLRR1 adversely affects oocyst development in mosquitoes.\",\n      \"method\": \"Co-immunoprecipitation (complex detection in parasite extracts), in vitro phosphatase activity assay, conditional genetic depletion with oocyst development quantification\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex detection, in vitro activity assay, and loss-of-function phenotype with defined developmental readout, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"35920043\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. berghei, Inhibitor 3 (I3) — a direct PbPP1 interactant — was found in the PbLRR1 interactome and was drastically hypophosphorylated in PbLRR1-depleted parasites, indicating that the PP1–LRR1 complex controls the phosphorylation status of I3, placing LRR11 (PbLRR1) upstream of I3 phosphorylation in the PP1 regulatory network.\",\n      \"method\": \"LRR1 interactome mass spectrometry, phospho-proteomics on PbLRR1-depleted parasites\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interactome MS combined with phospho-proteomics, single lab, two orthogonal methods\",\n      \"pmids\": [\"35920043\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"LRR11 (PfLRR1/PbLRR1) is a leucine-rich repeat protein that physically binds protein phosphatase type 1 (PP1) in both P. falciparum and P. berghei, inhibits PP1 catalytic activity, promotes cell cycle G2/M progression via PP1 suppression, and in P. berghei controls the phosphorylation status of PP1 regulator Inhibitor 3 (I3) to support efficient oocyst development in the mosquito.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"LRR11 (PF3D7_1123200; PfLRR1) is a leucine-rich repeat protein of Plasmodium that functions as a regulator of protein phosphatase type 1 (PP1), coupling PP1 activity to cell-cycle progression and parasite development [#0, #3]. In P. falciparum, LRR11 physically binds PfPP1 both in vitro and as a native complex in parasite extracts, and inhibits PfPP1 catalytic activity [#0]; it is one of 14 LRR-containing proteins in the parasite and is transcribed predominantly in late intraerythrocytic stages (late trophozoites and schizonts) [#2]. When expressed heterologously in Xenopus oocytes, LRR11 engages endogenous PP1 and drives G2/M progression, phenocopying PP1 inhibition and indicating that its suppression of PP1 can override the G2/M checkpoint [#1]. The P. berghei orthologue (PbLRR1) similarly complexes with and inhibits PbPP1 across asexual and sexual stages, and its depletion controls the phosphorylation status of the PP1 regulator Inhibitor 3 (I3) and impairs oocyst development in the mosquito, establishing LRR11 as a physiologically required node in the PP1 regulatory network [#3, #4]. Beyond its role as a PP1-binding regulator, no additional catalytic or structural mechanism for LRR11 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that LRR11 is not merely an LRR protein but a direct partner and inhibitor of PP1 defined its core biochemical function.\",\n      \"evidence\": \"GST pull-down, native parasite extract co-IP, and in vitro phosphatase assay in P. falciparum\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the LRR11–PfPP1 interaction not resolved\",\n        \"The PP1 residue or domain contacted by LRR11 not mapped\",\n        \"Whether inhibition is competitive with substrate or regulatory subunits unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"A heterologous Xenopus oocyte system linked LRR11's PP1 inhibition to a defined cell-cycle output, showing it can override the G2/M checkpoint.\",\n      \"evidence\": \"Xenopus oocyte GVBD assay with okadaic acid and anti-PP1 antibody controls\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"G2/M-promoting role not directly demonstrated in the parasite cell cycle\",\n        \"Downstream cell-cycle effectors of PP1 in Plasmodium not identified\",\n        \"Heterologous system may not recapitulate parasite regulatory context\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Cataloguing LRR11 among the parasite's LRR proteins and profiling its stage-specific transcription placed its expression at the late intraerythrocytic stages relevant to schizogony.\",\n      \"evidence\": \"Genome-wide identification, cloning/cDNA sequencing, and RT-qPCR stage profiling in P. falciparum\",\n      \"pmids\": [\"17689674\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Protein-level expression timing not established\",\n        \"Functional consequence of late-stage enrichment not tested\",\n        \"LRR motif contribution to PP1 binding not dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Genetic depletion in P. berghei moved LRR11 from an in vitro PP1 inhibitor to an in vivo developmental requirement, and phospho-proteomics placed it upstream of Inhibitor 3 phosphorylation.\",\n      \"evidence\": \"Co-IP, in vitro phosphatase assay, conditional depletion with oocyst quantification, interactome MS and phospho-proteomics in P. berghei\",\n      \"pmids\": [\"35920043\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which the PP1–LRR1 complex sets I3 phosphorylation not resolved\",\n        \"Whether I3 hypophosphorylation causes the oocyst defect not established\",\n        \"Asexual-stage essentiality of the orthologue not quantified in this readout\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How LRR11 integrates PP1 inhibition, I3 phosphorylation control, and cell-cycle/developmental timing into a single regulatory mechanism remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structure of LRR11 alone or bound to PP1\",\n        \"Direct in-parasite demonstration of G2/M control in P. falciparum absent\",\n        \"Causal chain from LRR11 loss to I3 hypophosphorylation to oocyst failure not established\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004864\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0019903\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000086\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"LRR11–PfPP1 complex (P. falciparum)\",\n      \"PbLRR1–PbPP1 complex (P. berghei)\"\n    ],\n    \"partners\": [\n      \"PfPP1 / PbPP1 (protein phosphatase type 1)\",\n      \"Inhibitor 3 (I3) — component of the PbLRR1 interactome (P. berghei)\"\n    ],\n    \"other_free_text\": [\n      \"One of 14 LRR-containing proteins in P. falciparum, containing 4–10 LRR motifs [#2].\",\n      \"Transcribed predominantly in late intraerythrocytic stages (late trophozoites and schizonts) [#2].\",\n      \"Genetic depletion of the P. berghei orthologue impairs oocyst development in the mosquito [#3].\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_1123200","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_1032800, PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1123200","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0925100","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0921000","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"LRR11","evaluation":null}