{"gene":"PF3D7_1106800","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2019,"finding":"Recombinant pTKL pseudokinase domain is able to bind ATP but lacks catalytic activity, consistent with its annotation as a pseudokinase; key catalytic residues are absent from the primary structure.","method":"Recombinant protein biochemical assay (ATP binding and kinase activity assay); primary structure analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assay on recombinant domain, single lab, single study","pmids":["31148576"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"The SAM motif of PF3D7_1106800 (pTKL) interacts with P. falciparum SERA5, identifying SERA5 as a binding partner.","method":"Protein-protein interaction assay (binding via SAM motif, inferred from pulldown/co-IP context described in the abstract)","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (motif-based interaction), no independent replication","pmids":["31148576"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"The RVxF motif of PF3D7_1106800 (pTKL) interacts with P. falciparum protein phosphatase type 1 (PP1), and this interaction modulates PP1 catalytic activity in a heterologous model in an RVxF-dependent manner, suggesting a scaffolding/regulatory role.","method":"Motif-based interaction assay; heterologous model PP1 activity assay with RVxF mutant","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional mutagenesis of RVxF motif combined with PP1 activity assay in heterologous model, single lab","pmids":["31148576"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"During trophozoite stages, PbpTKL (the P. berghei ortholog of PF3D7_1106800) is exported to infected erythrocytes, where it forms complexes with proteins involved in cytoskeletal organization or host cell maturation and homeostasis.","method":"Subcellular localization (live imaging/fractionation) and interactome analysis in P. berghei-infected erythrocytes","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment plus interactome identification, single lab, two orthogonal methods","pmids":["31148576"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"finding":"Genetic deletion or knockdown of PbpTKL (P. berghei ortholog of PF3D7_1106800) produced viable parasites with no detectable effect on intra-erythrocytic development or gametocyte emergence, indicating functional redundancy during these stages.","method":"Genetic knockout and knockdown in P. berghei with phenotypic readout (intra-erythrocytic development and gametocyte production)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO/KD with defined phenotypic readout, single lab; finding is a negative phenotype (no effect), explicitly reported as such","pmids":["31148576"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1106800 (pTKL) is a catalytically inactive pseudokinase that can bind ATP but lacks kinase activity; it acts as a scaffolding protein, engaging PP1 via its RVxF motif (modulating PP1 activity) and SERA5 via its SAM motif, and its P. berghei ortholog is exported to infected erythrocytes during trophozoite stages where it forms complexes with host cytoskeletal/homeostasis proteins, yet its genetic deletion or knockdown in P. berghei has no detectable effect on intra-erythrocytic development or gametocyte emergence."},"narrative":{"mechanistic_narrative":"PF3D7_1106800 (pTKL) is a catalytically inactive pseudokinase of Plasmodium that functions as a scaffolding protein rather than an active enzyme: its pseudokinase domain retains the ability to bind ATP but lacks kinase activity, and key catalytic residues are absent from its primary structure [PMID:31148576]. pTKL engages host-cell and parasite regulatory machinery through defined short linear motifs — its RVxF motif binds P. falciparum protein phosphatase type 1 (PP1) and modulates PP1 catalytic activity in an RVxF-dependent manner, consistent with a scaffolding/regulatory role, while its SAM motif binds the parasite protease SERA5 [PMID:31148576]. In P. berghei, the pTKL ortholog is exported to infected erythrocytes during trophozoite stages, where it forms complexes with host proteins involved in cytoskeletal organization and cell homeostasis [PMID:31148576]; however, genetic deletion or knockdown of the P. berghei ortholog yields viable parasites with no detectable defect in intra-erythrocytic development or gametocyte emergence, indicating functional redundancy at these stages [PMID:31148576]. Beyond these motif-based interactions and the P. berghei export/dispensability data, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Establishing whether pTKL is a genuine kinase or a pseudokinase was needed to interpret its role; the finding showed it binds ATP but is catalytically dead, redefining it as a scaffold rather than a signaling enzyme.","evidence":"Recombinant pseudokinase domain ATP-binding and kinase activity assays plus primary structure analysis in P. falciparum","pmids":["31148576"],"confidence":"Medium","gaps":["Whether ATP binding has any regulatory or conformational consequence is untested","No structural model of the pseudokinase domain","In vitro recombinant domain only, not full-length protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Because pTKL lacks catalytic activity, identifying its binding partners was essential to assign function; motif mapping identified PP1 (via RVxF) and SERA5 (via SAM) as interactors and showed the RVxF interaction alters PP1 activity, supporting a scaffolding/regulatory role.","evidence":"Motif-based interaction assays and heterologous PP1 activity assay with RVxF mutant in P. falciparum","pmids":["31148576"],"confidence":"Medium","gaps":["PP1 modulation was measured in a heterologous system, not in the parasite","The SERA5 interaction rests on a single motif-based method without reciprocal validation","Direction and physiological consequence of PP1 modulation in vivo unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"The subcellular fate and interaction environment of pTKL were unknown; in P. berghei the ortholog was shown to be exported to infected erythrocytes during trophozoite stages and to associate with host cytoskeletal/homeostasis proteins, placing it at the host-parasite interface.","evidence":"Subcellular localization (imaging/fractionation) and interactome analysis in P. berghei-infected erythrocytes","pmids":["31148576"],"confidence":"Medium","gaps":["Host partners identified in P. berghei, not confirmed for P. falciparum pTKL","Functional consequence of host-cytoskeleton complexes not demonstrated","Export signal/mechanism not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"claim":"Whether pTKL is required for parasite growth was tested to gauge its importance; genetic deletion/knockdown of the P. berghei ortholog gave viable parasites with normal intra-erythrocytic development and gametocyte emergence, indicating functional redundancy at these stages.","evidence":"Genetic knockout and knockdown in P. berghei with phenotypic readouts for asexual development and gametocyte production","pmids":["31148576"],"confidence":"Medium","gaps":["Negative phenotype does not exclude roles in other life-cycle stages (e.g. transmission, liver stage)","Redundancy with sibling family members not directly tested","P. falciparum requirement not assessed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How the PP1- and SERA5-scaffolding activities of pTKL and its host-cell interactions integrate into a defined biological process in P. falciparum, and in which life-cycle stage pTKL is non-redundant, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No stage identified where pTKL is functionally required","Physiological readout of PP1 modulation in living parasites unknown","P. falciparum export and host-partner interactome not directly established"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PP1 (P. FALCIPARUM PROTEIN PHOSPHATASE TYPE 1) VIA RVXF MOTIF","SERA5 (P. FALCIPARUM) VIA SAM MOTIF","HOST ERYTHROCYTE CYTOSKELETAL/HOMEOSTASIS PROTEINS (P. BERGHEI ORTHOLOG)"],"other_free_text":["pTKL is a catalytically inactive pseudokinase lacking key catalytic residues but retaining ATP binding [#0].","Interactions are mediated by defined short linear motifs: RVxF (PP1) and SAM (SERA5) [#1, #2].","The P. berghei ortholog is dispensable for intra-erythrocytic development and gametocyte emergence, indicating functional redundancy at these stages [#4]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31148576","id":"PMC_31148576","title":"Plasmodium pseudo-Tyrosine Kinase-like binds PP1 and SERA5 and is exported to host erythrocytes.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31148576","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pTKL","PfpTKL","PbpTKL"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35920043","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pTKL"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4370,"output_tokens":1287,"usd":0.016207,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6168,"output_tokens":2550,"usd":0.047295,"stage2_stop_reason":"end_turn"},"total_usd":0.063502,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"Recombinant pTKL pseudokinase domain is able to bind ATP but lacks catalytic activity, consistent with its annotation as a pseudokinase; key catalytic residues are absent from the primary structure.\",\n      \"method\": \"Recombinant protein biochemical assay (ATP binding and kinase activity assay); primary structure analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assay on recombinant domain, single lab, single study\",\n      \"pmids\": [\"31148576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The SAM motif of PF3D7_1106800 (pTKL) interacts with P. falciparum SERA5, identifying SERA5 as a binding partner.\",\n      \"method\": \"Protein-protein interaction assay (binding via SAM motif, inferred from pulldown/co-IP context described in the abstract)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (motif-based interaction), no independent replication\",\n      \"pmids\": [\"31148576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The RVxF motif of PF3D7_1106800 (pTKL) interacts with P. falciparum protein phosphatase type 1 (PP1), and this interaction modulates PP1 catalytic activity in a heterologous model in an RVxF-dependent manner, suggesting a scaffolding/regulatory role.\",\n      \"method\": \"Motif-based interaction assay; heterologous model PP1 activity assay with RVxF mutant\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional mutagenesis of RVxF motif combined with PP1 activity assay in heterologous model, single lab\",\n      \"pmids\": [\"31148576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"During trophozoite stages, PbpTKL (the P. berghei ortholog of PF3D7_1106800) is exported to infected erythrocytes, where it forms complexes with proteins involved in cytoskeletal organization or host cell maturation and homeostasis.\",\n      \"method\": \"Subcellular localization (live imaging/fractionation) and interactome analysis in P. berghei-infected erythrocytes\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment plus interactome identification, single lab, two orthogonal methods\",\n      \"pmids\": [\"31148576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Genetic deletion or knockdown of PbpTKL (P. berghei ortholog of PF3D7_1106800) produced viable parasites with no detectable effect on intra-erythrocytic development or gametocyte emergence, indicating functional redundancy during these stages.\",\n      \"method\": \"Genetic knockout and knockdown in P. berghei with phenotypic readout (intra-erythrocytic development and gametocyte production)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO/KD with defined phenotypic readout, single lab; finding is a negative phenotype (no effect), explicitly reported as such\",\n      \"pmids\": [\"31148576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1106800 (pTKL) is a catalytically inactive pseudokinase that can bind ATP but lacks kinase activity; it acts as a scaffolding protein, engaging PP1 via its RVxF motif (modulating PP1 activity) and SERA5 via its SAM motif, and its P. berghei ortholog is exported to infected erythrocytes during trophozoite stages where it forms complexes with host cytoskeletal/homeostasis proteins, yet its genetic deletion or knockdown in P. berghei has no detectable effect on intra-erythrocytic development or gametocyte emergence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1106800 (pTKL) is a catalytically inactive pseudokinase of Plasmodium that functions as a scaffolding protein rather than an active enzyme: its pseudokinase domain retains the ability to bind ATP but lacks kinase activity, and key catalytic residues are absent from its primary structure [#0]. pTKL engages host-cell and parasite regulatory machinery through defined short linear motifs \\u2014 its RVxF motif binds P. falciparum protein phosphatase type 1 (PP1) and modulates PP1 catalytic activity in an RVxF-dependent manner, consistent with a scaffolding/regulatory role, while its SAM motif binds the parasite protease SERA5 [#1, #2]. In P. berghei, the pTKL ortholog is exported to infected erythrocytes during trophozoite stages, where it forms complexes with host proteins involved in cytoskeletal organization and cell homeostasis [#3]; however, genetic deletion or knockdown of the P. berghei ortholog yields viable parasites with no detectable defect in intra-erythrocytic development or gametocyte emergence, indicating functional redundancy at these stages [#4]. Beyond these motif-based interactions and the P. berghei export/dispensability data, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing whether pTKL is a genuine kinase or a pseudokinase was needed to interpret its role; the finding showed it binds ATP but is catalytically dead, redefining it as a scaffold rather than a signaling enzyme.\",\n      \"evidence\": \"Recombinant pseudokinase domain ATP-binding and kinase activity assays plus primary structure analysis in P. falciparum\",\n      \"pmids\": [\n        \"31148576\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether ATP binding has any regulatory or conformational consequence is untested\",\n        \"No structural model of the pseudokinase domain\",\n        \"In vitro recombinant domain only, not full-length protein\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Because pTKL lacks catalytic activity, identifying its binding partners was essential to assign function; motif mapping identified PP1 (via RVxF) and SERA5 (via SAM) as interactors and showed the RVxF interaction alters PP1 activity, supporting a scaffolding/regulatory role.\",\n      \"evidence\": \"Motif-based interaction assays and heterologous PP1 activity assay with RVxF mutant in P. falciparum\",\n      \"pmids\": [\n        \"31148576\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PP1 modulation was measured in a heterologous system, not in the parasite\",\n        \"The SERA5 interaction rests on a single motif-based method without reciprocal validation\",\n        \"Direction and physiological consequence of PP1 modulation in vivo unknown\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"The subcellular fate and interaction environment of pTKL were unknown; in P. berghei the ortholog was shown to be exported to infected erythrocytes during trophozoite stages and to associate with host cytoskeletal/homeostasis proteins, placing it at the host-parasite interface.\",\n      \"evidence\": \"Subcellular localization (imaging/fractionation) and interactome analysis in P. berghei-infected erythrocytes\",\n      \"pmids\": [\n        \"31148576\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Host partners identified in P. berghei, not confirmed for P. falciparum pTKL\",\n        \"Functional consequence of host-cytoskeleton complexes not demonstrated\",\n        \"Export signal/mechanism not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether pTKL is required for parasite growth was tested to gauge its importance; genetic deletion/knockdown of the P. berghei ortholog gave viable parasites with normal intra-erythrocytic development and gametocyte emergence, indicating functional redundancy at these stages.\",\n      \"evidence\": \"Genetic knockout and knockdown in P. berghei with phenotypic readouts for asexual development and gametocyte production\",\n      \"pmids\": [\n        \"31148576\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative phenotype does not exclude roles in other life-cycle stages (e.g. transmission, liver stage)\",\n        \"Redundancy with sibling family members not directly tested\",\n        \"P. falciparum requirement not assessed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the PP1- and SERA5-scaffolding activities of pTKL and its host-cell interactions integrate into a defined biological process in P. falciparum, and in which life-cycle stage pTKL is non-redundant, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No stage identified where pTKL is functionally required\",\n        \"Physiological readout of PP1 modulation in living parasites unknown\",\n        \"P. falciparum export and host-partner interactome not directly established\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0005524\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      },\n      {\n        \"term_id\": \"GO:0019903\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      },\n      {\n        \"term_id\": \"GO:0004860\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0020030\",\n        \"supporting_discovery_ids\": [\n          3\n        ]\n      },\n      {\n        \"term_id\": \"GO:0020002\",\n        \"supporting_discovery_ids\": [\n          3\n        ]\n      }\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\n      \"PP1 (P. falciparum protein phosphatase type 1) via RVxF motif\",\n      \"SERA5 (P. falciparum) via SAM motif\",\n      \"host erythrocyte cytoskeletal/homeostasis proteins (P. berghei ortholog)\"\n    ],\n    \"other_free_text\": [\n      \"pTKL is a catalytically inactive pseudokinase lacking key catalytic residues but retaining ATP binding [#0].\",\n      \"Interactions are mediated by defined short linear motifs: RVxF (PP1) and SAM (SERA5) [#1, #2].\",\n      \"The P. berghei ortholog is dispensable for intra-erythrocytic development and gametocyte emergence, indicating functional redundancy at these stages [#4].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1106800","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1106800","name":null,"product":"pseudo-tyrosine kinase-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0940100","name":null,"product":"pseudo-tyrosine kinase-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0904400","name":null,"product":"pseudo-tyrosine kinase-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"pTKL","evaluation":null}