{"gene":"PF3D7_0110600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2009,"finding":"PIP5K (PF3D7_0110600) encodes a bifunctional protein with a C-terminal type I PIP5K domain that has catalytic specificity for phosphatidylinositol 4-phosphate (PtdIns4P), phosphorylating it to produce PtdIns(4,5)P2. The recombinant enzyme was demonstrated to be activated by myristoylated ARF1 but not by phosphatidic acid in vitro.","method":"Recombinant protein expression and in vitro lipid kinase assay with defined substrates; activation tested with ARF1 and phosphatidic acid","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic reconstitution with recombinant protein, substrate specificity defined, activator identified, single lab but multiple orthogonal biochemical methods","pmids":["19171150"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"PIP5K (PF3D7_0110600) contains an unusual N-terminal domain with helix-loop-helix EF-hand-like motifs characteristic of the neuronal calcium sensor (NCS) family, physically fused to the C-terminal PIP5K catalytic domain — a domain architecture unique among eukaryotes at the time of characterization.","method":"Sequence analysis and domain characterization of the recombinant protein","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — domain identification supported by sequence analysis and recombinant protein work; functional link of NCS domain to calcium-dependent regulation proposed but not directly tested experimentally","pmids":["19171150"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"In Plasmodium berghei ookinetes, the PIP5K ortholog (PBANKA_020310) is phosphorylated in a PKG-dependent and GCβ-dependent manner, placing it downstream of cGMP-PKG signalling in the phosphoinositide biosynthetic pathway that controls Ca2+ release required for gliding motility and gametocyte activation.","method":"Phosphoproteomic analysis of gliding ookinetes with PKG inhibitor and gcβ disruption; genetic epistasis by knockout of gcβ","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phosphoproteomic identification of regulated sites combined with genetic disruption of upstream kinase; single lab but uses orthogonal approaches (chemical inhibition + genetic KO)","pmids":["24594931"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"PIP5K (PF3D7_0110600) was identified as a yeast two-hybrid interaction partner of PfHSP70-2 in P. falciparum, consistent with its involvement in ARF1-regulated secretory trafficking; ARF1 itself is also a PfHSP70-2 interactor.","method":"Yeast two-hybrid interaction screen; mass spectrometry peptide mapping of affinity-purified proteins","journal":"Heliyon","confidence":"Low","confidence_rationale":"Tier 3 / Weak — yeast two-hybrid data only, single lab, no in-parasite validation of the interaction reported in the abstract","pmids":["32529065"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIP5K (PF3D7_0110600) is a bifunctional P. falciparum enzyme with a C-terminal type I PI4P 5-kinase domain that phosphorylates PtdIns4P to generate PtdIns(4,5)P2 and an N-terminal NCS-family EF-hand-like domain; its catalytic activity is stimulated by ARF1 (but not phosphatidic acid) in vitro, and its P. berghei ortholog is phosphorylated downstream of PKG/GCβ signalling, positioning PIP5K in a cGMP→PKG→phosphoinositide→Ca2+ cascade essential for ookinete gliding motility and gametocyte activation."},"narrative":{"mechanistic_narrative":"PIP5K (PF3D7_0110600) is a bifunctional Plasmodium falciparum lipid kinase that catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to generate PtdIns(4,5)P2, thereby feeding the parasite's phosphoinositide biosynthetic pathway [PMID:19171150]. The recombinant enzyme is a type I PIP5K whose catalytic activity is stimulated by myristoylated ARF1 but not by phosphatidic acid in vitro, linking its activity to ARF1-dependent regulation [PMID:19171150]. Its C-terminal catalytic domain is fused to an unusual N-terminal domain bearing helix-loop-helix EF-hand-like motifs of the neuronal calcium sensor (NCS) family, a domain architecture that was unique among eukaryotes at the time of characterization [PMID:19171150]. In the P. berghei ookinete, the PIP5K ortholog is phosphorylated in a PKG- and GCβ-dependent manner, placing the enzyme downstream of cGMP-PKG signalling in a phosphoinositide pathway that controls Ca2+ release required for gliding motility and gametocyte activation [PMID:24594931]. Beyond its ARF1-stimulated PtdIns4P kinase activity, its regulatory partnerships in P. falciparum have not been characterized in the available corpus, aside from a single yeast two-hybrid report of interaction with PfHSP70-2 [PMID:32529065].","teleology":[{"year":2009,"claim":"Establishing the enzymatic identity of PF3D7_0110600 answered whether the parasite encodes a dedicated PtdIns4P 5-kinase and how its activity is regulated.","evidence":"Recombinant protein expression with in vitro lipid kinase assays on defined substrates and testing of ARF1 and phosphatidic acid as activators","pmids":["19171150"],"confidence":"High","gaps":["Whether ARF1 stimulation operates on the enzyme in the parasite in vivo was not tested","No structural model of the catalytic or regulatory interface was determined","The physiological source and pool of the PtdIns4P substrate was not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Domain analysis revealed an NCS-family EF-hand-like N-terminal module fused to the kinase, raising the possibility that PIP5K activity is coupled to calcium sensing.","evidence":"Sequence analysis and domain characterization of the recombinant protein","pmids":["19171150"],"confidence":"Medium","gaps":["The functional link of the NCS domain to calcium-dependent regulation was proposed but not directly tested","Whether the EF-hand motifs bind Ca2+ was not demonstrated","The effect of the N-terminal domain on catalytic output was not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Phosphoproteomics placed the PIP5K ortholog downstream of PKG/GCβ signalling, connecting phosphoinositide production to the cGMP cascade that drives motility and gametocyte activation.","evidence":"Phosphoproteomic analysis of gliding P. berghei ookinetes with PKG inhibition and gcβ genetic disruption","pmids":["24594931"],"confidence":"Medium","gaps":["Shown in P. berghei ookinetes, not in P. falciparum","The functional consequence of the specific phosphorylation event on kinase activity was not determined","Whether PKG phosphorylates PIP5K directly or via an intermediate kinase is unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"A protein interaction screen linked PIP5K to PfHSP70-2, hinting at a physical connection to ARF1-regulated secretory trafficking.","evidence":"Yeast two-hybrid interaction screen with mass spectrometry mapping of affinity-purified proteins","pmids":["32529065"],"confidence":"Low","gaps":["Yeast two-hybrid only, with no in-parasite validation of the interaction","No reciprocal or biochemical confirmation of direct binding","Functional relevance of the interaction to PIP5K activity was not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether the NCS EF-hand domain confers direct Ca2+ regulation of PIP5K activity, and whether the PKG-dependent phosphorylation seen in P. berghei governs enzymatic output and PtdIns(4,5)P2 production in P. falciparum, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct test of calcium binding or calcium-dependent activity","No genetic loss-of-function characterization of PF3D7_0110600 in P. falciparum","No demonstration that PKG-dependent phosphorylation alters catalytic activity"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ARF1 (MYRISTOYLATED, IN VITRO ACTIVATOR) [#0]","PFHSP70-2 (YEAST TWO-HYBRID) [#3]"],"other_free_text":["Bifunctional protein: N-terminal NCS-family EF-hand-like domain fused to a C-terminal type I PIP5K catalytic domain [#1]","Catalytic activity stimulated by myristoylated ARF1 but not phosphatidic acid in vitro [#0]","P. berghei ortholog (PBANKA_020310) phosphorylated in a PKG- and GCβ-dependent manner, downstream of cGMP-PKG signalling [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21208444","id":"PMC_21208444","title":"Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discovery.","date":"2011","source":"BMC evolutionary biology","url":"https://pubmed.ncbi.nlm.nih.gov/21208444","citation_count":86,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19171150","id":"PMC_19171150","title":"A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP-ribosylation factor in Plasmodium falciparum.","date":"2009","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19171150","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K","phosphatidylinositol-4-phosphate 5-kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39639029","id":"","title":"Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39639029","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34102588","id":"","title":"Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.","date":"2021","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/34102588","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37939186","id":"","title":"Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness.","date":"2023","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/37939186","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32529065","id":"","title":"Identification of Plasmodium falciparum HSP70-2 as a resident of the Plasmodium export compartment.","date":"2020","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/32529065","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32745103","id":"","title":"Population genomics identifies a distinct Plasmodium vivax population on the China-Myanmar border of Southeast Asia.","date":"2020","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32745103","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37791074","id":"","title":"Regulation of phosphoinositide metabolism in Apicomplexan parasites.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/37791074","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35755845","id":"","title":"Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35755845","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32144363","id":"","title":"Detection of the in vitro modulation of Plasmodium falciparum Arf1 by Sec7 and ArfGAP domains using a colorimetric plate-based assay.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32144363","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27111866","id":"","title":"The development of malaria parasites in the mosquito midgut.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27111866","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24594931","id":"","title":"Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.","date":"2014","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/24594931","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28494763","id":"","title":"Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/28494763","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21518218","id":"","title":"Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation.","date":"2011","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21518218","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30533418","id":"","title":"Pathways of host cell exit by intracellular pathogens.","date":"2018","source":"Microbial cell (Graz, Austria)","url":"https://pubmed.ncbi.nlm.nih.gov/30533418","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24244373","id":"","title":"Genome-wide analysis of the phosphoinositide kinome from two ciliates reveals novel evolutionary links for phosphoinositide kinases in eukaryotic cells.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24244373","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP5K"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19555,"output_tokens":1254,"usd":0.038738,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6172,"output_tokens":2384,"usd":0.04523,"stage2_stop_reason":"end_turn"},"total_usd":0.083968,"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\": 2009,\n      \"finding\": \"PIP5K (PF3D7_0110600) encodes a bifunctional protein with a C-terminal type I PIP5K domain that has catalytic specificity for phosphatidylinositol 4-phosphate (PtdIns4P), phosphorylating it to produce PtdIns(4,5)P2. The recombinant enzyme was demonstrated to be activated by myristoylated ARF1 but not by phosphatidic acid in vitro.\",\n      \"method\": \"Recombinant protein expression and in vitro lipid kinase assay with defined substrates; activation tested with ARF1 and phosphatidic acid\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic reconstitution with recombinant protein, substrate specificity defined, activator identified, single lab but multiple orthogonal biochemical methods\",\n      \"pmids\": [\"19171150\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PIP5K (PF3D7_0110600) contains an unusual N-terminal domain with helix-loop-helix EF-hand-like motifs characteristic of the neuronal calcium sensor (NCS) family, physically fused to the C-terminal PIP5K catalytic domain — a domain architecture unique among eukaryotes at the time of characterization.\",\n      \"method\": \"Sequence analysis and domain characterization of the recombinant protein\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — domain identification supported by sequence analysis and recombinant protein work; functional link of NCS domain to calcium-dependent regulation proposed but not directly tested experimentally\",\n      \"pmids\": [\"19171150\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Plasmodium berghei ookinetes, the PIP5K ortholog (PBANKA_020310) is phosphorylated in a PKG-dependent and GCβ-dependent manner, placing it downstream of cGMP-PKG signalling in the phosphoinositide biosynthetic pathway that controls Ca2+ release required for gliding motility and gametocyte activation.\",\n      \"method\": \"Phosphoproteomic analysis of gliding ookinetes with PKG inhibitor and gcβ disruption; genetic epistasis by knockout of gcβ\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phosphoproteomic identification of regulated sites combined with genetic disruption of upstream kinase; single lab but uses orthogonal approaches (chemical inhibition + genetic KO)\",\n      \"pmids\": [\"24594931\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PIP5K (PF3D7_0110600) was identified as a yeast two-hybrid interaction partner of PfHSP70-2 in P. falciparum, consistent with its involvement in ARF1-regulated secretory trafficking; ARF1 itself is also a PfHSP70-2 interactor.\",\n      \"method\": \"Yeast two-hybrid interaction screen; mass spectrometry peptide mapping of affinity-purified proteins\",\n      \"journal\": \"Heliyon\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — yeast two-hybrid data only, single lab, no in-parasite validation of the interaction reported in the abstract\",\n      \"pmids\": [\"32529065\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PIP5K (PF3D7_0110600) is a bifunctional P. falciparum enzyme with a C-terminal type I PI4P 5-kinase domain that phosphorylates PtdIns4P to generate PtdIns(4,5)P2 and an N-terminal NCS-family EF-hand-like domain; its catalytic activity is stimulated by ARF1 (but not phosphatidic acid) in vitro, and its P. berghei ortholog is phosphorylated downstream of PKG/GCβ signalling, positioning PIP5K in a cGMP→PKG→phosphoinositide→Ca2+ cascade essential for ookinete gliding motility and gametocyte activation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIP5K (PF3D7_0110600) is a bifunctional Plasmodium falciparum lipid kinase that catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to generate PtdIns(4,5)P2, thereby feeding the parasite's phosphoinositide biosynthetic pathway [#0]. The recombinant enzyme is a type I PIP5K whose catalytic activity is stimulated by myristoylated ARF1 but not by phosphatidic acid in vitro, linking its activity to ARF1-dependent regulation [#0]. Its C-terminal catalytic domain is fused to an unusual N-terminal domain bearing helix-loop-helix EF-hand-like motifs of the neuronal calcium sensor (NCS) family, a domain architecture that was unique among eukaryotes at the time of characterization [#1]. In the P. berghei ookinete, the PIP5K ortholog is phosphorylated in a PKG- and GCβ-dependent manner, placing the enzyme downstream of cGMP-PKG signalling in a phosphoinositide pathway that controls Ca2+ release required for gliding motility and gametocyte activation [#2]. Beyond its ARF1-stimulated PtdIns4P kinase activity, its regulatory partnerships in P. falciparum have not been characterized in the available corpus, aside from a single yeast two-hybrid report of interaction with PfHSP70-2 [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing the enzymatic identity of PF3D7_0110600 answered whether the parasite encodes a dedicated PtdIns4P 5-kinase and how its activity is regulated.\",\n      \"evidence\": \"Recombinant protein expression with in vitro lipid kinase assays on defined substrates and testing of ARF1 and phosphatidic acid as activators\",\n      \"pmids\": [\"19171150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ARF1 stimulation operates on the enzyme in the parasite in vivo was not tested\",\n        \"No structural model of the catalytic or regulatory interface was determined\",\n        \"The physiological source and pool of the PtdIns4P substrate was not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Domain analysis revealed an NCS-family EF-hand-like N-terminal module fused to the kinase, raising the possibility that PIP5K activity is coupled to calcium sensing.\",\n      \"evidence\": \"Sequence analysis and domain characterization of the recombinant protein\",\n      \"pmids\": [\"19171150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The functional link of the NCS domain to calcium-dependent regulation was proposed but not directly tested\",\n        \"Whether the EF-hand motifs bind Ca2+ was not demonstrated\",\n        \"The effect of the N-terminal domain on catalytic output was not measured\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Phosphoproteomics placed the PIP5K ortholog downstream of PKG/GCβ signalling, connecting phosphoinositide production to the cGMP cascade that drives motility and gametocyte activation.\",\n      \"evidence\": \"Phosphoproteomic analysis of gliding P. berghei ookinetes with PKG inhibition and gcβ genetic disruption\",\n      \"pmids\": [\"24594931\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Shown in P. berghei ookinetes, not in P. falciparum\",\n        \"The functional consequence of the specific phosphorylation event on kinase activity was not determined\",\n        \"Whether PKG phosphorylates PIP5K directly or via an intermediate kinase is unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A protein interaction screen linked PIP5K to PfHSP70-2, hinting at a physical connection to ARF1-regulated secretory trafficking.\",\n      \"evidence\": \"Yeast two-hybrid interaction screen with mass spectrometry mapping of affinity-purified proteins\",\n      \"pmids\": [\"32529065\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Yeast two-hybrid only, with no in-parasite validation of the interaction\",\n        \"No reciprocal or biochemical confirmation of direct binding\",\n        \"Functional relevance of the interaction to PIP5K activity was not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the NCS EF-hand domain confers direct Ca2+ regulation of PIP5K activity, and whether the PKG-dependent phosphorylation seen in P. berghei governs enzymatic output and PtdIns(4,5)P2 production in P. falciparum, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct test of calcium binding or calcium-dependent activity\",\n        \"No genetic loss-of-function characterization of PF3D7_0110600 in P. falciparum\",\n        \"No demonstration that PKG-dependent phosphorylation alters catalytic activity\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016308\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046854\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0007205\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ARF1 (myristoylated, in vitro activator) [#0]\", \"PfHSP70-2 (yeast two-hybrid) [#3]\"],\n    \"other_free_text\": [\n      \"Bifunctional protein: N-terminal NCS-family EF-hand-like domain fused to a C-terminal type I PIP5K catalytic domain [#1]\",\n      \"Catalytic activity stimulated by myristoylated ARF1 but not phosphatidic acid in vitro [#0]\",\n      \"P. berghei ortholog (PBANKA_020310) phosphorylated in a PKG- and GCβ-dependent manner, downstream of cGMP-PKG signalling [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0110600","name":null,"product":"phosphatidylinositol-4-phosphate 5-kinase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0203100","name":null,"product":"phosphatidylinositol-4-phosphate 5-kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0203300","name":null,"product":"phosphatidylinositol-4-phosphate 5-kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIP5K","evaluation":null}