{"gene":"PF3D7_1432400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2006,"finding":"PfLRR1 (the P. falciparum SDS22 orthologue, a leucine-rich repeat protein) physically interacts with PfPP1 (protein phosphatase type 1) as shown by GST pull-down assay, and this complex is present in parasite extracts. PfLRR1 inhibits PfPP1 phosphatase activity in vitro.","method":"GST pull-down assay, co-immunoprecipitation from parasite extracts, enzymatic phosphatase activity assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pull-down and in vitro enzymatic assay, single lab, two orthogonal methods","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"When expressed in Xenopus oocytes, PfLRR1 (the P. falciparum SDS22/LRR orthologue) interacted with endogenous PP1 and promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), mimicking the effect of PP1 inhibition by okadaic acid or anti-PP1 antibodies.","method":"Xenopus oocyte functional assay, GVBD readout, comparison with okadaic acid and anti-PP1 antibody treatment","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional heterologous system with orthogonal chemical and antibody controls, single lab","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"PF3D7_1432400 (LRR5) was identified as one of 14 LRR-encoding genes in P. falciparum; real-time quantitative PCR showed it is transcribed during the intraerythrocytic lifecycle, with most PfLRR genes highly expressed in late trophozoites and schizonts.","method":"Genome analysis, cDNA cloning and sequencing, real-time quantitative PCR","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional profiling of the gene family; no direct functional experiment specific to LRR5/PF3D7_1432400","pmids":["17689674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"In P. berghei, the LRR1 orthologue (PbLRR1) forms a complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic depletion of PbLRR1 adversely affects oocyst development. Interactome and phospho-proteomics identified novel PbLRR1/PbPP1 partners, and Inhibitor 3 (I3) was found to be hypophosphorylated in PbLRR1-depleted parasites, suggesting the PP1-LRR1 complex controls the phosphorylation status of I3.","method":"Co-immunoprecipitation, phosphatase activity assay, genetic knockdown/depletion, interactome (mass spectrometry), phospho-proteomics","journal":"Open biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, enzymatic assay, genetic KD, MS interactome, phospho-proteomics) in a single rigorous study","pmids":["35920043"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"Disruption of LRR5 (PF3D7_1432400) in P. falciparum by piggyBac mutagenesis reshapes the parasite transcriptome across multiple intraerythrocytic stages: protein folding, protein export, and host-cell remodeling pathways (including Maurer's cleft components, PTEX export machinery, and HSP70-x) are downregulated, while cytoplasmic heat-shock proteins and translation-associated genes are upregulated. LRR5 disruption also causes premature activation of gametocyte-associated transcriptional programs including elevated Pfs16 protein expression and accelerated transcriptional progression through trophozoite, merozoite, and gametocyte gene clusters.","method":"Single-cell RNA sequencing (scRNA-seq) of unsynchronized cultures, pseudotime analysis, Pfs16 protein-level confirmation by immunoassay, isogenic piggyBac mutant (LRR5pB) vs. wild-type NF54","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function mutant with defined transcriptional and protein-level phenotype, single lab, orthogonal scRNA-seq and protein validation","pmids":["42294623"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]}],"current_model":"LRR5 (PF3D7_1432400) is a leucine-rich repeat protein in P. falciparum whose orthologue in P. falciparum (PfLRR1) and P. berghei (PbLRR1) physically associates with protein phosphatase type 1 (PP1) and inhibits its activity, thereby influencing cell cycle progression; in P. falciparum specifically, disruption of LRR5 downregulates protein folding, export, and host-cell remodeling pathways while upregulating stress-response genes and prematurely activating gametocyte commitment programs, indicating LRR5 links proteostasis and host-cell remodeling to developmental timing and transmission."},"narrative":{"mechanistic_narrative":"LRR5 (PF3D7_1432400) is a Plasmodium falciparum leucine-rich repeat protein that couples protein phosphatase type 1 (PP1) regulation to developmental timing and host-cell remodeling during the intraerythrocytic cycle [PMID:16629662, PMID:42294623]. It is the P. falciparum SDS22 orthologue and physically associates with PfPP1, inhibiting the phosphatase in vitro; in a heterologous Xenopus oocyte system it drives progression through the G2/M checkpoint and germinal vesicle breakdown in a manner mimicking PP1 inhibition, linking LRR5 to cell-cycle control [PMID:16629662]. Loss-of-function analysis in P. falciparum shows that disruption of LRR5 downregulates protein folding, protein export, and host-cell remodeling machinery (Maurer's cleft components, the PTEX export apparatus, and HSP70-x) while upregulating cytoplasmic heat-shock and translation genes, and prematurely activates gametocyte-associated programs including elevated Pfs16, indicating LRR5 restrains developmental progression toward transmission [PMID:42294623]. The P. berghei orthologue PbLRR1 similarly forms a stage-spanning complex with PbPP1 and controls the phosphorylation status of Inhibitor 3, and its depletion impairs oocyst development [PMID:35920043]. Beyond the PP1 interaction and these transcriptional and cell-cycle phenotypes, no substrate specificity or structural mechanism for LRR5 itself has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing whether the P. falciparum SDS22-type LRR protein regulates a phosphatase answered how PP1 activity might be controlled in the parasite, and showed LRR5's orthologue is a direct PP1 inhibitor.","evidence":"GST pull-down, co-immunoprecipitation from parasite extracts, and in vitro phosphatase activity assay showing PfLRR1-PfPP1 binding and inhibition","pmids":["16629662"],"confidence":"Medium","gaps":["Interaction and inhibition shown for the PfLRR1 orthologue, not resolved to the PF3D7_1432400 gene product specifically","No structural basis for PP1 binding or inhibition","Physiological substrates of the PP1-LRR complex not identified"],"attribution":[]},{"year":2006,"claim":"A heterologous functional test addressed whether LRR-mediated PP1 inhibition has cell-cycle consequences, showing the orthologue promotes G2/M progression like PP1 inhibition.","evidence":"Xenopus oocyte assay with GVBD readout, benchmarked against okadaic acid and anti-PP1 antibody treatment","pmids":["16629662"],"confidence":"Medium","gaps":["Effect demonstrated in a non-parasite heterologous system","Direct cell-cycle role in P. falciparum not tested here","Does not identify the downstream phospho-targets that drive checkpoint progression"],"attribution":[]},{"year":2007,"claim":"Family-level cataloguing placed PF3D7_1432400 among P. falciparum LRR genes and established that it is transcribed across the intraerythrocytic cycle, providing baseline expression context.","evidence":"Genome analysis, cDNA cloning, and real-time quantitative PCR across the intraerythrocytic lifecycle","pmids":["17689674"],"confidence":"Low","gaps":["Transcriptional survey only; no function assigned to PF3D7_1432400","Does not distinguish LRR5 from sibling LRR family members functionally","Protein-level expression and localization not addressed"],"attribution":[]},{"year":2022,"claim":"A rigorous orthologue study in P. berghei answered what the PP1-LRR complex controls and whether it matters for transmission, identifying Inhibitor 3 as a phospho-target and showing a role in oocyst development.","evidence":"Co-IP, phosphatase activity assay, genetic depletion, MS interactome, and phospho-proteomics in P. berghei","pmids":["35920043"],"confidence":"High","gaps":["Shown for the P. berghei orthologue PbLRR1, not for P. falciparum PF3D7_1432400 directly","Mechanistic link between I3 dephosphorylation and oocyst phenotype not resolved","Does not establish which interactome partners are functionally required"],"attribution":[]},{"year":2026,"claim":"Loss-of-function analysis in P. falciparum answered what disrupting LRR5 does to parasite biology, revealing coordinate downregulation of proteostasis and host-cell remodeling pathways alongside premature commitment to gametocytogenesis.","evidence":"piggyBac mutant (LRR5pB) vs. NF54 profiled by single-cell RNA-seq with pseudotime analysis and Pfs16 protein confirmation","pmids":["42294623"],"confidence":"Medium","gaps":["Transcriptional phenotype does not establish which effects are direct versus secondary","Whether the developmental phenotype depends on PP1 inhibition is not tested","piggyBac insertion effects on the gene product not molecularly resolved"],"attribution":[]},{"year":null,"claim":"How PP1 regulation by LRR5 mechanistically connects to the observed proteostasis, host-cell remodeling, and premature gametocyte-commitment phenotypes in P. falciparum remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct demonstration that PF3D7_1432400 binds or inhibits PfPP1 (shown only for the orthologue)","Substrates dephosphorylated under LRR5 control in P. falciparum not identified","No structural model or defined domain determinants for LRR5 function"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PP1-LRR (SDS22-type) complex with PfPP1 (P. falciparum orthologue) / PbPP1 (P. berghei orthologue)"],"partners":["PFPP1 / PP1 (PROTEIN PHOSPHATASE TYPE 1)","INHIBITOR 3 (I3) — PHOSPHO-TARGET OF THE PBLRR1/PBPP1 COMPLEX IN P. BERGHEI"],"other_free_text":["PF3D7_1432400 is the P. falciparum SDS22 orthologue and one of 14 LRR-encoding genes in the genome; transcribed across the intraerythrocytic cycle [#2].","Direct biochemical PP1 binding and inhibition are established for the orthologues PfLRR1 and PbLRR1; the P. falciparum LRR5 gene product itself is characterized primarily by its loss-of-function transcriptional phenotype [#0, #3, #4].","P. falciparum LRR5 disruption downregulates PTEX export machinery, Maurer's cleft components, and HSP70-x, upregulates cytoplasmic heat-shock and translation genes, and prematurely activates gametocyte programs with elevated Pfs16 [#4]."]}},"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":"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},{"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":["LRR5","leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5028,"output_tokens":1688,"usd":0.020202,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6679,"output_tokens":2793,"usd":0.05161,"stage2_stop_reason":"end_turn"},"total_usd":0.071812,"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\": 2006,\n      \"finding\": \"PfLRR1 (the P. falciparum SDS22 orthologue, a leucine-rich repeat protein) physically interacts with PfPP1 (protein phosphatase type 1) as shown by GST pull-down assay, and this complex is present in parasite extracts. PfLRR1 inhibits PfPP1 phosphatase activity in vitro.\",\n      \"method\": \"GST pull-down assay, co-immunoprecipitation from parasite extracts, enzymatic phosphatase activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pull-down and in vitro enzymatic assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"When expressed in Xenopus oocytes, PfLRR1 (the P. falciparum SDS22/LRR orthologue) interacted with endogenous PP1 and promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), mimicking the effect of PP1 inhibition by okadaic acid or anti-PP1 antibodies.\",\n      \"method\": \"Xenopus oocyte functional assay, GVBD readout, comparison with okadaic acid and anti-PP1 antibody treatment\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional heterologous system with orthogonal chemical and antibody controls, single lab\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PF3D7_1432400 (LRR5) was identified as one of 14 LRR-encoding genes in P. falciparum; real-time quantitative PCR showed it is transcribed during the intraerythrocytic lifecycle, with most PfLRR genes highly expressed in late trophozoites and schizonts.\",\n      \"method\": \"Genome analysis, cDNA cloning and sequencing, real-time quantitative PCR\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional profiling of the gene family; no direct functional experiment specific to LRR5/PF3D7_1432400\",\n      \"pmids\": [\"17689674\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. berghei, the LRR1 orthologue (PbLRR1) forms a complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic depletion of PbLRR1 adversely affects oocyst development. Interactome and phospho-proteomics identified novel PbLRR1/PbPP1 partners, and Inhibitor 3 (I3) was found to be hypophosphorylated in PbLRR1-depleted parasites, suggesting the PP1-LRR1 complex controls the phosphorylation status of I3.\",\n      \"method\": \"Co-immunoprecipitation, phosphatase activity assay, genetic knockdown/depletion, interactome (mass spectrometry), phospho-proteomics\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, enzymatic assay, genetic KD, MS interactome, phospho-proteomics) in a single rigorous study\",\n      \"pmids\": [\"35920043\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Disruption of LRR5 (PF3D7_1432400) in P. falciparum by piggyBac mutagenesis reshapes the parasite transcriptome across multiple intraerythrocytic stages: protein folding, protein export, and host-cell remodeling pathways (including Maurer's cleft components, PTEX export machinery, and HSP70-x) are downregulated, while cytoplasmic heat-shock proteins and translation-associated genes are upregulated. LRR5 disruption also causes premature activation of gametocyte-associated transcriptional programs including elevated Pfs16 protein expression and accelerated transcriptional progression through trophozoite, merozoite, and gametocyte gene clusters.\",\n      \"method\": \"Single-cell RNA sequencing (scRNA-seq) of unsynchronized cultures, pseudotime analysis, Pfs16 protein-level confirmation by immunoassay, isogenic piggyBac mutant (LRR5pB) vs. wild-type NF54\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function mutant with defined transcriptional and protein-level phenotype, single lab, orthogonal scRNA-seq and protein validation\",\n      \"pmids\": [\"42294623\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    }\n  ],\n  \"current_model\": \"LRR5 (PF3D7_1432400) is a leucine-rich repeat protein in P. falciparum whose orthologue in P. falciparum (PfLRR1) and P. berghei (PbLRR1) physically associates with protein phosphatase type 1 (PP1) and inhibits its activity, thereby influencing cell cycle progression; in P. falciparum specifically, disruption of LRR5 downregulates protein folding, export, and host-cell remodeling pathways while upregulating stress-response genes and prematurely activating gametocyte commitment programs, indicating LRR5 links proteostasis and host-cell remodeling to developmental timing and transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LRR5 (PF3D7_1432400) is a Plasmodium falciparum leucine-rich repeat protein that couples protein phosphatase type 1 (PP1) regulation to developmental timing and host-cell remodeling during the intraerythrocytic cycle [#0, #4]. It is the P. falciparum SDS22 orthologue and physically associates with PfPP1, inhibiting the phosphatase in vitro; in a heterologous Xenopus oocyte system it drives progression through the G2/M checkpoint and germinal vesicle breakdown in a manner mimicking PP1 inhibition, linking LRR5 to cell-cycle control [#0, #1]. Loss-of-function analysis in P. falciparum shows that disruption of LRR5 downregulates protein folding, protein export, and host-cell remodeling machinery (Maurer's cleft components, the PTEX export apparatus, and HSP70-x) while upregulating cytoplasmic heat-shock and translation genes, and prematurely activates gametocyte-associated programs including elevated Pfs16, indicating LRR5 restrains developmental progression toward transmission [#4]. The P. berghei orthologue PbLRR1 similarly forms a stage-spanning complex with PbPP1 and controls the phosphorylation status of Inhibitor 3, and its depletion impairs oocyst development [#3]. Beyond the PP1 interaction and these transcriptional and cell-cycle phenotypes, no substrate specificity or structural mechanism for LRR5 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing whether the P. falciparum SDS22-type LRR protein regulates a phosphatase answered how PP1 activity might be controlled in the parasite, and showed LRR5's orthologue is a direct PP1 inhibitor.\",\n      \"evidence\": \"GST pull-down, co-immunoprecipitation from parasite extracts, and in vitro phosphatase activity assay showing PfLRR1-PfPP1 binding and inhibition\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction and inhibition shown for the PfLRR1 orthologue, not resolved to the PF3D7_1432400 gene product specifically\", \"No structural basis for PP1 binding or inhibition\", \"Physiological substrates of the PP1-LRR complex not identified\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"A heterologous functional test addressed whether LRR-mediated PP1 inhibition has cell-cycle consequences, showing the orthologue promotes G2/M progression like PP1 inhibition.\",\n      \"evidence\": \"Xenopus oocyte assay with GVBD readout, benchmarked against okadaic acid and anti-PP1 antibody treatment\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effect demonstrated in a non-parasite heterologous system\", \"Direct cell-cycle role in P. falciparum not tested here\", \"Does not identify the downstream phospho-targets that drive checkpoint progression\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Family-level cataloguing placed PF3D7_1432400 among P. falciparum LRR genes and established that it is transcribed across the intraerythrocytic cycle, providing baseline expression context.\",\n      \"evidence\": \"Genome analysis, cDNA cloning, and real-time quantitative PCR across the intraerythrocytic lifecycle\",\n      \"pmids\": [\"17689674\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Transcriptional survey only; no function assigned to PF3D7_1432400\", \"Does not distinguish LRR5 from sibling LRR family members functionally\", \"Protein-level expression and localization not addressed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"A rigorous orthologue study in P. berghei answered what the PP1-LRR complex controls and whether it matters for transmission, identifying Inhibitor 3 as a phospho-target and showing a role in oocyst development.\",\n      \"evidence\": \"Co-IP, phosphatase activity assay, genetic depletion, MS interactome, and phospho-proteomics in P. berghei\",\n      \"pmids\": [\"35920043\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Shown for the P. berghei orthologue PbLRR1, not for P. falciparum PF3D7_1432400 directly\", \"Mechanistic link between I3 dephosphorylation and oocyst phenotype not resolved\", \"Does not establish which interactome partners are functionally required\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Loss-of-function analysis in P. falciparum answered what disrupting LRR5 does to parasite biology, revealing coordinate downregulation of proteostasis and host-cell remodeling pathways alongside premature commitment to gametocytogenesis.\",\n      \"evidence\": \"piggyBac mutant (LRR5pB) vs. NF54 profiled by single-cell RNA-seq with pseudotime analysis and Pfs16 protein confirmation\",\n      \"pmids\": [\"42294623\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional phenotype does not establish which effects are direct versus secondary\", \"Whether the developmental phenotype depends on PP1 inhibition is not tested\", \"piggyBac insertion effects on the gene product not molecularly resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PP1 regulation by LRR5 mechanistically connects to the observed proteostasis, host-cell remodeling, and premature gametocyte-commitment phenotypes in P. falciparum remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct demonstration that PF3D7_1432400 binds or inhibits PfPP1 (shown only for the orthologue)\", \"Substrates dephosphorylated under LRR5 control in P. falciparum not identified\", \"No structural model or defined domain determinants for LRR5 function\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004865\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000079\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0060255\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"PP1-LRR (SDS22-type) complex with PfPP1 (P. falciparum orthologue) / PbPP1 (P. berghei orthologue)\"\n    ],\n    \"partners\": [\n      \"PfPP1 / PP1 (protein phosphatase type 1)\",\n      \"Inhibitor 3 (I3) — phospho-target of the PbLRR1/PbPP1 complex in P. berghei\"\n    ],\n    \"other_free_text\": [\n      \"PF3D7_1432400 is the P. falciparum SDS22 orthologue and one of 14 LRR-encoding genes in the genome; transcribed across the intraerythrocytic cycle [#2].\",\n      \"Direct biochemical PP1 binding and inhibition are established for the orthologues PfLRR1 and PbLRR1; the P. falciparum LRR5 gene product itself is characterized primarily by its loss-of-function transcriptional phenotype [#0, #3, #4].\",\n      \"P. falciparum LRR5 disruption downregulates PTEX export machinery, Maurer's cleft components, and HSP70-x, upregulates cytoplasmic heat-shock and translation genes, and prematurely activates gametocyte programs with elevated Pfs16 [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1432400","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1012500","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0419000","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"LRR5","evaluation":null}