{"gene":"PF3D7_1427900","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2006,"finding":"PfLRR1 (the P. falciparum Sds22 orthologue) physically interacts with PfPP1 (protein phosphatase type 1), as demonstrated by GST pull-down assay and confirmed by co-immunoprecipitation from parasite extracts; 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":"High","confidence_rationale":"Tier 1–2 / Moderate — direct biochemical interaction confirmed by two orthogonal methods (pull-down + Co-IP) plus enzymatic inhibition assay in a single focused study","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"PfLRR1 expression in Xenopus oocytes promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), an effect consistent with inhibition of endogenous PP1; this functional outcome was phenocopied by anti-PP1 antibodies and okadaic acid treatment.","method":"Xenopus oocyte microinjection/expression system, GVBD assay, pharmacological controls (okadaic acid, anti-PP1 antibodies)","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — heterologous expression functional assay with multiple controls, single lab, single paper","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"PbLRR1 (the P. berghei orthologue of PfLRR1) forms a complex with PbPP1 in both asexual and sexual stages of the parasite and inhibits PbPP1 phosphatase activity; genetic depletion of PbLRR1 adversely affects oocyst development in mosquitoes.","method":"Co-immunoprecipitation, phosphatase activity assay, conditional genetic depletion (reverse genetics), oocyst phenotype analysis","journal":"Open biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — biochemical interaction + enzymatic inhibition assay + genetic KO phenotype, multiple orthogonal methods in one study","pmids":["35920043"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"Interactome and phospho-proteomics analysis of PbLRR1-depleted parasites identified Inhibitor 3 (I3) as drastically hypophosphorylated and present in the PbLRR1/PbPP1 complex, indicating that the phosphorylation status of PbI3 is under the control of the PP1-LRR1 complex.","method":"Interactome mass spectrometry, phospho-proteomics on PbLRR1-depleted parasites","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — mass spectrometry interactome + phosphoproteomics, single lab, single paper; functional significance inferred but not directly tested","pmids":["35920043"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1427900 (PfLRR1), the P. falciparum Sds22 orthologue, physically interacts with and inhibits protein phosphatase type 1 (PP1), thereby promoting progression through the G2/M cell cycle checkpoint; its P. berghei orthologue (PbLRR1) similarly complexes with and inhibits PP1 across asexual and sexual stages, is required for oocyst development, and regulates the phosphorylation status of PP1 Inhibitor 3 (I3) as part of the PP1-LRR1 complex."},"narrative":{"mechanistic_narrative":"PF3D7_1427900 (PfLRR1), the P. falciparum Sds22 orthologue, is a leucine-rich repeat regulator of protein phosphatase type 1 (PP1) that couples phosphatase control to cell cycle progression [PMID:16629662]. It physically binds PfPP1 and directly inhibits its phosphatase activity in vitro [PMID:16629662], and when expressed in Xenopus oocytes it drives progression through the G2/M checkpoint by inducing germinal vesicle breakdown, an outcome phenocopied by pharmacological PP1 inhibition [PMID:16629662]. This regulatory relationship is conserved in the rodent malaria parasite P. berghei, where the orthologue PbLRR1 complexes with and inhibits PbPP1 across both asexual and sexual stages, is required for normal oocyst development in the mosquito, and controls the phosphorylation status of PP1 Inhibitor 3 (I3), which is found within the PbLRR1/PbPP1 complex and becomes hypophosphorylated upon PbLRR1 depletion [PMID:35920043]. Beyond its role as a PP1-inhibitory subunit acting through cell cycle progression and the I3 regulatory node, no further mechanistic detail for this gene has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing whether PfLRR1 acts on the parasite phosphatase machinery, this work showed it is a direct physical and functional partner of PfPP1, defining it as a PP1 regulatory subunit rather than an orphan LRR protein.","evidence":"GST pull-down and co-immunoprecipitation from parasite extracts plus in vitro phosphatase activity assay, in P. falciparum","pmids":["16629662"],"confidence":"High","gaps":["Interaction interface and stoichiometry not resolved","In vivo requirement in P. falciparum asexual growth not tested","No structural model of the PfLRR1-PfPP1 complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"To connect the biochemical inhibition to a cellular process, heterologous expression showed PfLRR1 drives G2/M progression, linking PP1 inhibition to cell cycle checkpoint control.","evidence":"Xenopus oocyte expression with GVBD readout and okadaic acid / anti-PP1 antibody pharmacological controls, in P. falciparum","pmids":["16629662"],"confidence":"Medium","gaps":["Effect demonstrated in a heterologous oocyte system, not in the parasite itself","Endogenous parasite cell cycle role not directly measured","Downstream substrates dephosphorylated by PP1 during progression not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To test whether the PP1-inhibitory function has a genetic requirement in vivo, the P. berghei orthologue was shown to complex with and inhibit PbPP1 across stages and to be required for mosquito-stage oocyst development.","evidence":"Co-immunoprecipitation, phosphatase activity assay, and conditional genetic depletion with oocyst phenotype analysis, in P. berghei","pmids":["35920043"],"confidence":"High","gaps":["Whether the P. falciparum orthologue has the same oocyst/transmission requirement not directly tested","Mechanism linking PP1 inhibition to oocyst maturation unresolved","Essentiality in asexual blood stages not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"To map the regulatory output of the complex, interactome and phosphoproteomic profiling identified Inhibitor 3 (I3) as a complex member whose phosphorylation is controlled by the PP1-LRR1 module.","evidence":"Interactome mass spectrometry and phospho-proteomics on PbLRR1-depleted parasites, in P. berghei","pmids":["35920043"],"confidence":"Medium","gaps":["Functional consequence of I3 hypophosphorylation not directly tested","Whether I3 phosphorylation change is direct or indirect not established","Kinase(s) opposing PP1 on I3 not identified"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How PfLRR1-mediated PP1 inhibition is regulated during the parasite cell cycle and which parasite substrates are governed by the PfLRR1/PfPP1/I3 network in the human malaria parasite remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No PfLRR1 loss-of-function phenotype in P. falciparum","No structural characterization of the complex","Physiological substrates and cell cycle timing of PP1 inhibition unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfLRR1-PfPP1 complex","PbLRR1-PbPP1-I3 complex"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE 1)","PBPP1","PP1 INHIBITOR 3 (I3)"],"other_free_text":["PfLRR1 is described as the P. falciparum Sds22 orthologue [#0]","PbLRR1 depletion impairs oocyst development in the mosquito [#2]","PbLRR1 complexes with PP1 in both asexual and sexual stages [#2]"]}},"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":"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":"20421304","id":"PMC_20421304","title":"Plasmodium falciparum dynein light chain 1 interacts with actin/myosin during blood stage development.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20421304","citation_count":15,"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":"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":5601,"output_tokens":1576,"usd":0.020221,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5965,"output_tokens":2422,"usd":0.045187,"stage2_stop_reason":"end_turn"},"total_usd":0.065408,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are about PF3D7_1427900 specifically.\n\nPF3D7_1427900 is described as \"leucine-rich repeat protein\" and is the P. falciparum orthologue of Sds22/LRR1 based on the corpus. Let me check each paper:\n\n1. **PMID:16629662** — PfLRR1, the P. falciparum Sds22 orthologue. This is about PF3D7_1427900 (PfLRR1). ✓\n2. **PMID:16714563** — SmLRR (Schistosoma mansoni) with cross-reactivity to a P. falciparum gene product. This is about SmLRR primarily; the P. falciparum gene is only mentioned as having 57% similarity — no mechanistic experiments on the Pf protein itself. EXCLUDE.\n3. **PMID:20421304** — PfDLC1 (dynein light chain 1), a different LRR family member. This is NOT PF3D7_1427900. EXCLUDE.\n4. **PMID:35920043** — PbLRR1, the P. berghei orthologue of PfLRR1/Sds22. This is the same gene in P. berghei. ✓\n5. **PMID:42294623** — LRR5 (PF3D7_1432400), a different gene entirely. EXCLUDE.\n\nNow extracting findings from papers 1 and 4:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"PfLRR1 (the P. falciparum Sds22 orthologue) physically interacts with PfPP1 (protein phosphatase type 1), as demonstrated by GST pull-down assay and confirmed by co-immunoprecipitation from parasite extracts; 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\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct biochemical interaction confirmed by two orthogonal methods (pull-down + Co-IP) plus enzymatic inhibition assay in a single focused study\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"PfLRR1 expression in Xenopus oocytes promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), an effect consistent with inhibition of endogenous PP1; this functional outcome was phenocopied by anti-PP1 antibodies and okadaic acid treatment.\",\n      \"method\": \"Xenopus oocyte microinjection/expression system, GVBD assay, pharmacological controls (okadaic acid, anti-PP1 antibodies)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — heterologous expression functional assay with multiple controls, single lab, single paper\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PbLRR1 (the P. berghei orthologue of PfLRR1) forms a complex with PbPP1 in both asexual and sexual stages of the parasite and inhibits PbPP1 phosphatase activity; genetic depletion of PbLRR1 adversely affects oocyst development in mosquitoes.\",\n      \"method\": \"Co-immunoprecipitation, phosphatase activity assay, conditional genetic depletion (reverse genetics), oocyst phenotype analysis\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — biochemical interaction + enzymatic inhibition assay + genetic KO phenotype, multiple orthogonal methods in one study\",\n      \"pmids\": [\"35920043\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Interactome and phospho-proteomics analysis of PbLRR1-depleted parasites identified Inhibitor 3 (I3) as drastically hypophosphorylated and present in the PbLRR1/PbPP1 complex, indicating that the phosphorylation status of PbI3 is under the control of the PP1-LRR1 complex.\",\n      \"method\": \"Interactome mass spectrometry, phospho-proteomics on PbLRR1-depleted parasites\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — mass spectrometry interactome + phosphoproteomics, single lab, single paper; functional significance inferred but not directly tested\",\n      \"pmids\": [\"35920043\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1427900 (PfLRR1), the P. falciparum Sds22 orthologue, physically interacts with and inhibits protein phosphatase type 1 (PP1), thereby promoting progression through the G2/M cell cycle checkpoint; its P. berghei orthologue (PbLRR1) similarly complexes with and inhibits PP1 across asexual and sexual stages, is required for oocyst development, and regulates the phosphorylation status of PP1 Inhibitor 3 (I3) as part of the PP1-LRR1 complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1427900 (PfLRR1), the P. falciparum Sds22 orthologue, is a leucine-rich repeat regulator of protein phosphatase type 1 (PP1) that couples phosphatase control to cell cycle progression [#0, #1]. It physically binds PfPP1 and directly inhibits its phosphatase activity in vitro [#0], and when expressed in Xenopus oocytes it drives progression through the G2/M checkpoint by inducing germinal vesicle breakdown, an outcome phenocopied by pharmacological PP1 inhibition [#1]. This regulatory relationship is conserved in the rodent malaria parasite P. berghei, where the orthologue PbLRR1 complexes with and inhibits PbPP1 across both asexual and sexual stages, is required for normal oocyst development in the mosquito, and controls the phosphorylation status of PP1 Inhibitor 3 (I3), which is found within the PbLRR1/PbPP1 complex and becomes hypophosphorylated upon PbLRR1 depletion [#2, #3]. Beyond its role as a PP1-inhibitory subunit acting through cell cycle progression and the I3 regulatory node, no further mechanistic detail for this gene has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing whether PfLRR1 acts on the parasite phosphatase machinery, this work showed it is a direct physical and functional partner of PfPP1, defining it as a PP1 regulatory subunit rather than an orphan LRR protein.\",\n      \"evidence\": \"GST pull-down and co-immunoprecipitation from parasite extracts plus in vitro phosphatase activity assay, in P. falciparum\",\n      \"pmids\": [\n        \"16629662\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Interaction interface and stoichiometry not resolved\",\n        \"In vivo requirement in P. falciparum asexual growth not tested\",\n        \"No structural model of the PfLRR1-PfPP1 complex\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"To connect the biochemical inhibition to a cellular process, heterologous expression showed PfLRR1 drives G2/M progression, linking PP1 inhibition to cell cycle checkpoint control.\",\n      \"evidence\": \"Xenopus oocyte expression with GVBD readout and okadaic acid / anti-PP1 antibody pharmacological controls, in P. falciparum\",\n      \"pmids\": [\n        \"16629662\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Effect demonstrated in a heterologous oocyte system, not in the parasite itself\",\n        \"Endogenous parasite cell cycle role not directly measured\",\n        \"Downstream substrates dephosphorylated by PP1 during progression not identified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To test whether the PP1-inhibitory function has a genetic requirement in vivo, the P. berghei orthologue was shown to complex with and inhibit PbPP1 across stages and to be required for mosquito-stage oocyst development.\",\n      \"evidence\": \"Co-immunoprecipitation, phosphatase activity assay, and conditional genetic depletion with oocyst phenotype analysis, in P. berghei\",\n      \"pmids\": [\n        \"35920043\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the P. falciparum orthologue has the same oocyst/transmission requirement not directly tested\",\n        \"Mechanism linking PP1 inhibition to oocyst maturation unresolved\",\n        \"Essentiality in asexual blood stages not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To map the regulatory output of the complex, interactome and phosphoproteomic profiling identified Inhibitor 3 (I3) as a complex member whose phosphorylation is controlled by the PP1-LRR1 module.\",\n      \"evidence\": \"Interactome mass spectrometry and phospho-proteomics on PbLRR1-depleted parasites, in P. berghei\",\n      \"pmids\": [\n        \"35920043\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of I3 hypophosphorylation not directly tested\",\n        \"Whether I3 phosphorylation change is direct or indirect not established\",\n        \"Kinase(s) opposing PP1 on I3 not identified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfLRR1-mediated PP1 inhibition is regulated during the parasite cell cycle and which parasite substrates are governed by the PfLRR1/PfPP1/I3 network in the human malaria parasite remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No PfLRR1 loss-of-function phenotype in P. falciparum\",\n        \"No structural characterization of the complex\",\n        \"Physiological substrates and cell cycle timing of PP1 inhibition unresolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0004865\",\n        \"supporting_discovery_ids\": [\n          0,\n          2\n        ]\n      },\n      {\n        \"term_id\": \"GO:0019903\",\n        \"supporting_discovery_ids\": [\n          0,\n          2\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0000086\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0035825\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"PfLRR1-PfPP1 complex\",\n      \"PbLRR1-PbPP1-I3 complex\"\n    ],\n    \"partners\": [\n      \"PfPP1 (protein phosphatase type 1)\",\n      \"PbPP1\",\n      \"PP1 Inhibitor 3 (I3)\"\n    ],\n    \"other_free_text\": [\n      \"PfLRR1 is described as the P. falciparum Sds22 orthologue [#0]\",\n      \"PbLRR1 depletion impairs oocyst development in the mosquito [#2]\",\n      \"PbLRR1 complexes with PP1 in both asexual and sexual stages [#2]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1427900","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_1427900","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1016700","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1330800","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}