{"gene":"PF3D7_0309000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2004,"finding":"Recombinant YVH1 (PfYVH1/PF3D7_0309000) dephosphorylates both phosphoserine and phosphotyrosine residues in vitro, confirming dual-specificity phosphatase activity. The protein contains 2 mol of zinc per mol protein in its C-terminal zinc-binding domain (one histidine, eight cysteines). Mutation of specific Cys residues in the putative zinc finger region abolished zinc binding and drastically reduced phosphatase activity, indicating an allosteric role of zinc in catalysis.","method":"Recombinant protein expression, in vitro phosphatase assay with phosphoserine/phosphotyrosine substrates, zinc content analysis, site-directed mutagenesis of Cys residues","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with mutagenesis demonstrating allosteric zinc mechanism, single lab but multiple orthogonal methods (activity assay, zinc quantification, mutagenesis)","pmids":["14698441"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"YVH1 (PfYVH1) is expressed in essentially all erythrocytic stages of P. falciparum and shuttles between the nucleus and the cytoplasm in a stage-specific manner.","method":"Stage-specific expression analysis and subcellular fractionation/localization across erythrocytic stages","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — localization determined by fractionation in a single lab without functional consequence directly demonstrated","pmids":["14698441"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"YVH1 (PfYVH1) physically interacts with PfPES, a Plasmodium ortholog of the nuclear pescadillo protein, implicating YVH1 in regulation of parasitic development.","method":"Co-immunoprecipitation / protein-protein interaction assay (interaction of recombinant or expressed proteins)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown/interaction assay; functional consequence inferred but not directly demonstrated by epistasis or rescue","pmids":["14698441"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0309000 (YVH1) encodes a dual-specificity phosphatase in P. falciparum that dephosphorylates both phosphoserine and phosphotyrosine residues; its catalytic activity depends allosterically on zinc coordinated by a C-terminal zinc-binding domain (2 mol Zn/mol protein), as shown by Cys-to-Ala mutagenesis that abolishes zinc binding and dramatically reduces activity; the protein shuttles between nucleus and cytoplasm in a stage-specific manner across erythrocytic development, and interacts with the nuclear pescadillo ortholog PfPES."},"narrative":{"mechanistic_narrative":"PF3D7_0309000 (YVH1) encodes a dual-specificity protein phosphatase of P. falciparum that dephosphorylates both phosphoserine and phosphotyrosine residues in vitro, and whose catalytic activity depends allosterically on zinc coordinated within a C-terminal zinc-binding domain [PMID:14698441]. The recombinant protein binds two moles of zinc per mole of protein through a cluster of one histidine and eight cysteines, and Cys-to-Ala mutations that abolish zinc binding drastically reduce phosphatase activity, establishing zinc as an allosteric requirement for catalysis [PMID:14698441]. Across erythrocytic development the protein is expressed at essentially all stages and shuttles between the nucleus and cytoplasm in a stage-specific manner [PMID:14698441], and it physically associates with PfPES, a Plasmodium ortholog of the nuclear pescadillo protein, linking YVH1 to the regulation of parasite development [PMID:14698441]. Beyond these findings, the physiological substrates of YVH1 and the functional consequences of its nucleocytoplasmic shuttling and PfPES interaction have not been characterized in the available corpus.","teleology":[{"year":2004,"claim":"Whether PF3D7_0309000 is a genuine catalytically active phosphatase and how its activity is controlled was unknown; demonstrating dual-specificity activity and a zinc-dependent allosteric mechanism established both its enzymatic identity and its regulatory logic.","evidence":"Recombinant protein in vitro phosphatase assays on phosphoserine/phosphotyrosine substrates, zinc quantification, and site-directed Cys mutagenesis","pmids":["14698441"],"confidence":"High","gaps":["No physiological substrate identified in cells","Structural basis of zinc-dependent allostery not resolved","Whether zinc occupancy is regulated in vivo is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Where and when the phosphatase acts during the blood stage was undefined; showing stage-wide expression with stage-specific nucleocytoplasmic shuttling placed the enzyme in a dynamic compartmental context during erythrocytic development.","evidence":"Stage-specific expression analysis and subcellular fractionation across erythrocytic stages","pmids":["14698441"],"confidence":"Medium","gaps":["Functional consequence of shuttling not demonstrated","Trigger and machinery controlling nuclear-cytoplasmic partitioning unknown","Localization inferred from fractionation without independent imaging in the same report"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"The lack of any known interaction partner left the enzyme's cellular pathway undefined; identifying a physical interaction with the nuclear pescadillo ortholog PfPES tied YVH1 to a candidate developmental-regulatory context.","evidence":"Co-immunoprecipitation / protein-protein interaction assay","pmids":["14698441"],"confidence":"Medium","gaps":["Single pulldown without reciprocal validation","Whether PfPES is a dephosphorylation substrate versus a scaffolding partner is unknown","Functional consequence of the interaction not tested by epistasis or rescue"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo substrates, the biological purpose of stage-specific shuttling, and the functional role of the PfPES interaction in parasite development remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No physiological substrate identified","No genetic loss-of-function phenotype in the corpus","Functional meaning of the YVH1-PfPES association undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPES (PLASMODIUM PESCADILLO ORTHOLOG)"],"other_free_text":["Binds 2 mol zinc per mol protein via a C-terminal zinc-binding domain (one histidine, eight cysteines); zinc plays an allosteric role in catalysis [#0]","Expressed across essentially all erythrocytic stages with stage-specific nucleocytoplasmic shuttling [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18793411","id":"PMC_18793411","title":"The protein-phosphatome of the human malaria parasite Plasmodium falciparum.","date":"2008","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18793411","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"14698441","id":"PMC_14698441","title":"A zinc-binding dual-specificity YVH1 phosphatase in the malaria parasite, Plasmodium falciparum, and its interaction with the nuclear protein, pescadillo.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/14698441","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["YVH1","PfYVH1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33934569","id":"","title":"A Plasmodium falciparum protein tyrosine phosphatase inhibitor identified from the ChEMBL-NTD database blocks parasite growth.","date":"2021","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/33934569","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["YVH1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35792443","id":"","title":"Phosphatase inhibitors BVT-948 and alexidine dihydrochloride inhibit sexual development of the malaria parasite Plasmodium berghei.","date":"2022","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/35792443","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["YVH1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35336160","id":"","title":"Deciphering the Role of Protein Phosphatases in Apicomplexa: The Future of Innovative Therapeutics?","date":"2022","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/35336160","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["YVH1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25425018","id":"","title":"Genome wide in silico analysis of Plasmodium falciparum phosphatome.","date":"2014","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/25425018","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["YVH1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7701,"output_tokens":931,"usd":0.018534,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5703,"output_tokens":1968,"usd":0.038858,"stage2_stop_reason":"end_turn"},"total_usd":0.057392,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"Recombinant YVH1 (PfYVH1/PF3D7_0309000) dephosphorylates both phosphoserine and phosphotyrosine residues in vitro, confirming dual-specificity phosphatase activity. The protein contains 2 mol of zinc per mol protein in its C-terminal zinc-binding domain (one histidine, eight cysteines). Mutation of specific Cys residues in the putative zinc finger region abolished zinc binding and drastically reduced phosphatase activity, indicating an allosteric role of zinc in catalysis.\",\n      \"method\": \"Recombinant protein expression, in vitro phosphatase assay with phosphoserine/phosphotyrosine substrates, zinc content analysis, site-directed mutagenesis of Cys residues\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with mutagenesis demonstrating allosteric zinc mechanism, single lab but multiple orthogonal methods (activity assay, zinc quantification, mutagenesis)\",\n      \"pmids\": [\"14698441\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"YVH1 (PfYVH1) is expressed in essentially all erythrocytic stages of P. falciparum and shuttles between the nucleus and the cytoplasm in a stage-specific manner.\",\n      \"method\": \"Stage-specific expression analysis and subcellular fractionation/localization across erythrocytic stages\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization determined by fractionation in a single lab without functional consequence directly demonstrated\",\n      \"pmids\": [\"14698441\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"YVH1 (PfYVH1) physically interacts with PfPES, a Plasmodium ortholog of the nuclear pescadillo protein, implicating YVH1 in regulation of parasitic development.\",\n      \"method\": \"Co-immunoprecipitation / protein-protein interaction assay (interaction of recombinant or expressed proteins)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown/interaction assay; functional consequence inferred but not directly demonstrated by epistasis or rescue\",\n      \"pmids\": [\"14698441\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0309000 (YVH1) encodes a dual-specificity phosphatase in P. falciparum that dephosphorylates both phosphoserine and phosphotyrosine residues; its catalytic activity depends allosterically on zinc coordinated by a C-terminal zinc-binding domain (2 mol Zn/mol protein), as shown by Cys-to-Ala mutagenesis that abolishes zinc binding and dramatically reduces activity; the protein shuttles between nucleus and cytoplasm in a stage-specific manner across erythrocytic development, and interacts with the nuclear pescadillo ortholog PfPES.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0309000 (YVH1) encodes a dual-specificity protein phosphatase of P. falciparum that dephosphorylates both phosphoserine and phosphotyrosine residues in vitro, and whose catalytic activity depends allosterically on zinc coordinated within a C-terminal zinc-binding domain [#0]. The recombinant protein binds two moles of zinc per mole of protein through a cluster of one histidine and eight cysteines, and Cys-to-Ala mutations that abolish zinc binding drastically reduce phosphatase activity, establishing zinc as an allosteric requirement for catalysis [#0]. Across erythrocytic development the protein is expressed at essentially all stages and shuttles between the nucleus and cytoplasm in a stage-specific manner [#1], and it physically associates with PfPES, a Plasmodium ortholog of the nuclear pescadillo protein, linking YVH1 to the regulation of parasite development [#2]. Beyond these findings, the physiological substrates of YVH1 and the functional consequences of its nucleocytoplasmic shuttling and PfPES interaction have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Whether PF3D7_0309000 is a genuine catalytically active phosphatase and how its activity is controlled was unknown; demonstrating dual-specificity activity and a zinc-dependent allosteric mechanism established both its enzymatic identity and its regulatory logic.\",\n      \"evidence\": \"Recombinant protein in vitro phosphatase assays on phosphoserine/phosphotyrosine substrates, zinc quantification, and site-directed Cys mutagenesis\",\n      \"pmids\": [\"14698441\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No physiological substrate identified in cells\",\n        \"Structural basis of zinc-dependent allostery not resolved\",\n        \"Whether zinc occupancy is regulated in vivo is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Where and when the phosphatase acts during the blood stage was undefined; showing stage-wide expression with stage-specific nucleocytoplasmic shuttling placed the enzyme in a dynamic compartmental context during erythrocytic development.\",\n      \"evidence\": \"Stage-specific expression analysis and subcellular fractionation across erythrocytic stages\",\n      \"pmids\": [\"14698441\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of shuttling not demonstrated\",\n        \"Trigger and machinery controlling nuclear-cytoplasmic partitioning unknown\",\n        \"Localization inferred from fractionation without independent imaging in the same report\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"The lack of any known interaction partner left the enzyme's cellular pathway undefined; identifying a physical interaction with the nuclear pescadillo ortholog PfPES tied YVH1 to a candidate developmental-regulatory context.\",\n      \"evidence\": \"Co-immunoprecipitation / protein-protein interaction assay\",\n      \"pmids\": [\"14698441\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single pulldown without reciprocal validation\",\n        \"Whether PfPES is a dephosphorylation substrate versus a scaffolding partner is unknown\",\n        \"Functional consequence of the interaction not tested by epistasis or rescue\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo substrates, the biological purpose of stage-specific shuttling, and the functional role of the PfPES interaction in parasite development remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No physiological substrate identified\",\n        \"No genetic loss-of-function phenotype in the corpus\",\n        \"Functional meaning of the YVH1-PfPES association undetermined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008138\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004725\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004722\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006470\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfPES (Plasmodium pescadillo ortholog)\"],\n    \"other_free_text\": [\n      \"Binds 2 mol zinc per mol protein via a C-terminal zinc-binding domain (one histidine, eight cysteines); zinc plays an allosteric role in catalysis [#0]\",\n      \"Expressed across essentially all erythrocytic stages with stage-specific nucleocytoplasmic shuttling [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0309000","name":null,"product":"dual specificity protein phosphatase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0407200","name":null,"product":"dual specificity protein phosphatase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0833700","name":null,"product":"dual specificity protein phosphatase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"YVH1","evaluation":null}