{"gene":"PF3D7_1219700","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":1995,"finding":"RKIP (PF3D7_1219700) was identified as a putative phosphatidylethanolamine-binding protein in P. falciparum, with its primary structure determined, establishing it as a member of the PEBP sequence family.","method":"Primary structure determination / sequence analysis","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — sequence-based identification, no functional assay reported in abstract","pmids":["7637711"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"RKIP (PF3D7_1219700) is phosphorylated by PfCDPK1 in vitro, acting as a substrate with approximately 7-fold lower specific activity compared to casein; additionally, RKIP's presence in kinase assays enhances PfCDPK1 autophosphorylation ~5.5-fold while diminishing PfCDPK1 substrate (casein) phosphorylation activity, indicating RKIP acts as a regulator of PfCDPK1 kinase activity.","method":"Recombinant protein expression, purification, and in vitro kinase assays","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro kinase assay with purified recombinant proteins, single lab, single method","pmids":["17123645"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"The crystal structure of the P. vivax RKIP ortholog was solved to 1.3 Å resolution by MAD phasing; the protein is topologically similar to other PEBP family members but contains a distinctive left-handed alpha-helical region at one side of the canonical phospholipid-binding site, suggesting it represents a structurally distinct subfamily of PEBP proteins.","method":"X-ray crystallography (MAD, 1.3 Å resolution)","journal":"Acta crystallographica. Section F, Structural biology and crystallization communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution crystal structure, single study, structural inference about functional motif without mutagenesis validation","pmids":["17329808"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2025,"finding":"RKIP (PF3D7_1219700) is a lipid-binding protein that interacts with phosphatidic acid and phosphorylated phosphatidylinositol lipids (including PtdIns(3)P) at physiological pH, a property dependent on conserved residues in the PEBP domain; mutation of a unique IKK motif within the PEBP domain reduces lipid interaction.","method":"Lipid-binding assays, site-directed mutagenesis, in silico docking","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (lipid binding assay, mutagenesis, in silico docking), single lab","pmids":["39842334"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"RKIP (PF3D7_1219700) physically interacts with PfCDPK1 both in vitro (ELISA) and within the parasite (immunofluorescence assay and proximity biotinylation); in the presence of a PfCDPK1 substrate, PfCDPK1 hyper-phosphorylates RKIP, leading to RKIP dissociation from PfCDPK1 and allowing PfCDPK1 to trans-phosphorylate its downstream substrates, establishing a substrate-competition regulatory mechanism.","method":"ELISA, immunofluorescence assay, proximity biotinylation (BioID), in vitro kinase assays","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods including in-parasite proximity biotinylation, IFA, and in vitro biochemical assays, single lab","pmids":["39842334"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"RKIP (PF3D7_1219700) is expressed throughout asexual schizogony with maximum expression in late schizonts, as determined by direct experimental characterization.","method":"Expression profiling (experimental, specific stage)","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method, expression localization with no direct functional consequence established in the abstract","pmids":["39842334"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1219700 (RKIP) is a phosphatidylethanolamine-binding protein (PEBP) family member in P. falciparum that binds phosphatidic acid and phosphorylated phosphatidylinositol lipids via its PEBP domain, physically interacts with and regulates the calcium-dependent protein kinase PfCDPK1: in the absence of competing substrate, RKIP enhances PfCDPK1 autophosphorylation while suppressing substrate phosphorylation, and upon substrate addition PfCDPK1 hyper-phosphorylates RKIP causing its dissociation and relieving inhibition to allow downstream substrate phosphorylation."},"narrative":{"mechanistic_narrative":"PF3D7_1219700 (RKIP) is a phosphatidylethanolamine-binding protein (PEBP)-family member of P. falciparum that functions as a lipid-binding regulator of the calcium-dependent protein kinase PfCDPK1 [PMID:7637711, PMID:39842334]. Through its PEBP domain it binds phosphatidic acid and phosphorylated phosphatidylinositol lipids including PtdIns(3)P at physiological pH, an interaction that depends on conserved PEBP-domain residues and on a distinctive IKK motif whose mutation reduces lipid binding [PMID:39842334]. RKIP physically associates with PfCDPK1 both in vitro and within the parasite [PMID:39842334]: as both a substrate and a regulator of the kinase, its presence enhances PfCDPK1 autophosphorylation while suppressing phosphorylation of competing substrates [PMID:17123645]. Upon addition of a PfCDPK1 substrate, the kinase hyper-phosphorylates RKIP, driving RKIP dissociation and relieving inhibition so that PfCDPK1 can trans-phosphorylate downstream substrates — a substrate-competition regulatory switch operative during asexual schizogony [PMID:39842334]. Beyond this PfCDPK1-regulatory role and its lipid-binding activity, no further cellular function of RKIP has been characterized in the available corpus.","teleology":[{"year":1995,"claim":"Establishing what kind of protein PF3D7_1219700 is: sequence determination placed it in the phosphatidylethanolamine-binding protein (PEBP) family, framing all subsequent lipid- and kinase-related hypotheses.","evidence":"Primary structure determination and sequence analysis in P. falciparum","pmids":["7637711"],"confidence":"Low","gaps":["No functional assay; family assignment is sequence-based only","No demonstration of lipid binding or any partner at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Testing whether RKIP has a functional relationship to a parasite kinase: in vitro assays showed it is a PfCDPK1 substrate and, more importantly, a modulator that boosts kinase autophosphorylation while dampening phosphorylation of other substrates.","evidence":"Recombinant protein expression, purification, and in vitro kinase assays with purified proteins","pmids":["17123645"],"confidence":"Medium","gaps":["Interaction shown only in vitro, not in the parasite","Structural basis of the regulatory effect unresolved","Physiological consequence of the regulation not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Determining the structural framework of the protein: a 1.3 Å ortholog structure confirmed the PEBP fold but revealed a distinctive left-handed alpha-helical element beside the canonical phospholipid-binding site, defining a structurally distinct PEBP subfamily.","evidence":"X-ray crystallography (MAD, 1.3 Å) of the P. vivax RKIP ortholog","pmids":["17329808"],"confidence":"Medium","gaps":["Structure is of the P. vivax ortholog, not the P. falciparum protein itself","Functional role of the distinctive helical motif not tested by mutagenesis","No ligand bound in the structure"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2025,"claim":"Defining the lipid-binding activity implied by the PEBP fold: RKIP binds phosphatidic acid and phosphorylated phosphatidylinositols via conserved PEBP residues and a unique IKK motif, giving the family assignment concrete biochemical meaning.","evidence":"Lipid-binding assays, site-directed mutagenesis, and in silico docking in P. falciparum","pmids":["39842334"],"confidence":"Medium","gaps":["Physiological lipid ligand in vivo not established","Link between lipid binding and PfCDPK1 regulation not directly tested","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Resolving how RKIP regulates PfCDPK1 mechanistically and whether the interaction occurs in cells: RKIP interacts with PfCDPK1 in vitro and in the parasite, and substrate-driven hyper-phosphorylation of RKIP triggers its dissociation, establishing a substrate-competition switch that relieves inhibition of downstream substrate phosphorylation.","evidence":"ELISA, immunofluorescence, proximity biotinylation (BioID), and in vitro kinase assays in P. falciparum","pmids":["39842334"],"confidence":"High","gaps":["Downstream PfCDPK1 substrates released by the switch not identified","In-parasite functional consequence of RKIP loss not tested (no knockout/knockdown phenotype)","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether RKIP is essential for asexual development and how its lipid binding is coupled to PfCDPK1 regulation in vivo remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function phenotype for RKIP reported","Physiological trigger and biological output of the substrate-competition switch unknown","Relationship between membrane lipid binding and kinase regulation untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFCDPK1"],"other_free_text":["PEBP-family protein with a PEBP domain harboring conserved lipid-binding residues and a distinctive IKK motif required for lipid interaction [#3].","Binds phosphatidic acid and phosphorylated phosphatidylinositols including PtdIns(3)P at physiological pH [#3].","Acts as both substrate and regulator of PfCDPK1: enhances kinase autophosphorylation and suppresses competing substrate phosphorylation [#1].","Substrate-competition switch: PfCDPK1 hyper-phosphorylation of RKIP drives dissociation and relieves inhibition [#4].","P. vivax ortholog structure (1.3 Å) shows PEBP fold with a distinctive left-handed alpha-helical element defining a distinct subfamily [#2].","Expressed throughout asexual schizogony, peaking in late schizonts [#5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"7637711","id":"PMC_7637711","title":"The primary structure of a putative phosphatidylethanolamine-binding protein from Plasmodium falciparum.","date":"1995","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/7637711","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17123645","id":"PMC_17123645","title":"Raf kinase inhibitor protein affects activity of Plasmodium falciparum calcium-dependent protein kinase 1.","date":"2006","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17123645","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RKIP","raf kinase inhibitor"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17329808","id":"PMC_17329808","title":"The structure of Plasmodium vivax phosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix.","date":"2007","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/17329808","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RKIP","raf kinase inhibitor"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39842334","id":"PMC_39842334","title":"Plasmodium falciparum raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39842334","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RKIP","raf kinase inhibitor"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41633918","id":"PMC_41633918","title":"Corrigendum to \"Plasmodium falciparum Raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion\" [Biochem. Biophys. Res. Commun. 749 (2025) 151350].","date":"2026","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/41633918","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["raf kinase inhibitor"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4664,"output_tokens":1695,"usd":0.019709,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6696,"output_tokens":2697,"usd":0.050452,"stage2_stop_reason":"end_turn"},"total_usd":0.070161,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1995,\n      \"finding\": \"RKIP (PF3D7_1219700) was identified as a putative phosphatidylethanolamine-binding protein in P. falciparum, with its primary structure determined, establishing it as a member of the PEBP sequence family.\",\n      \"method\": \"Primary structure determination / sequence analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — sequence-based identification, no functional assay reported in abstract\",\n      \"pmids\": [\"7637711\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"RKIP (PF3D7_1219700) is phosphorylated by PfCDPK1 in vitro, acting as a substrate with approximately 7-fold lower specific activity compared to casein; additionally, RKIP's presence in kinase assays enhances PfCDPK1 autophosphorylation ~5.5-fold while diminishing PfCDPK1 substrate (casein) phosphorylation activity, indicating RKIP acts as a regulator of PfCDPK1 kinase activity.\",\n      \"method\": \"Recombinant protein expression, purification, and in vitro kinase assays\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro kinase assay with purified recombinant proteins, single lab, single method\",\n      \"pmids\": [\"17123645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The crystal structure of the P. vivax RKIP ortholog was solved to 1.3 Å resolution by MAD phasing; the protein is topologically similar to other PEBP family members but contains a distinctive left-handed alpha-helical region at one side of the canonical phospholipid-binding site, suggesting it represents a structurally distinct subfamily of PEBP proteins.\",\n      \"method\": \"X-ray crystallography (MAD, 1.3 Å resolution)\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology and crystallization communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution crystal structure, single study, structural inference about functional motif without mutagenesis validation\",\n      \"pmids\": [\"17329808\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RKIP (PF3D7_1219700) is a lipid-binding protein that interacts with phosphatidic acid and phosphorylated phosphatidylinositol lipids (including PtdIns(3)P) at physiological pH, a property dependent on conserved residues in the PEBP domain; mutation of a unique IKK motif within the PEBP domain reduces lipid interaction.\",\n      \"method\": \"Lipid-binding assays, site-directed mutagenesis, in silico docking\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (lipid binding assay, mutagenesis, in silico docking), single lab\",\n      \"pmids\": [\"39842334\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RKIP (PF3D7_1219700) physically interacts with PfCDPK1 both in vitro (ELISA) and within the parasite (immunofluorescence assay and proximity biotinylation); in the presence of a PfCDPK1 substrate, PfCDPK1 hyper-phosphorylates RKIP, leading to RKIP dissociation from PfCDPK1 and allowing PfCDPK1 to trans-phosphorylate its downstream substrates, establishing a substrate-competition regulatory mechanism.\",\n      \"method\": \"ELISA, immunofluorescence assay, proximity biotinylation (BioID), in vitro kinase assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods including in-parasite proximity biotinylation, IFA, and in vitro biochemical assays, single lab\",\n      \"pmids\": [\"39842334\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RKIP (PF3D7_1219700) is expressed throughout asexual schizogony with maximum expression in late schizonts, as determined by direct experimental characterization.\",\n      \"method\": \"Expression profiling (experimental, specific stage)\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method, expression localization with no direct functional consequence established in the abstract\",\n      \"pmids\": [\"39842334\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1219700 (RKIP) is a phosphatidylethanolamine-binding protein (PEBP) family member in P. falciparum that binds phosphatidic acid and phosphorylated phosphatidylinositol lipids via its PEBP domain, physically interacts with and regulates the calcium-dependent protein kinase PfCDPK1: in the absence of competing substrate, RKIP enhances PfCDPK1 autophosphorylation while suppressing substrate phosphorylation, and upon substrate addition PfCDPK1 hyper-phosphorylates RKIP causing its dissociation and relieving inhibition to allow downstream substrate phosphorylation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1219700 (RKIP) is a phosphatidylethanolamine-binding protein (PEBP)-family member of P. falciparum that functions as a lipid-binding regulator of the calcium-dependent protein kinase PfCDPK1 [#0, #4]. Through its PEBP domain it binds phosphatidic acid and phosphorylated phosphatidylinositol lipids including PtdIns(3)P at physiological pH, an interaction that depends on conserved PEBP-domain residues and on a distinctive IKK motif whose mutation reduces lipid binding [#3]. RKIP physically associates with PfCDPK1 both in vitro and within the parasite [#4]: as both a substrate and a regulator of the kinase, its presence enhances PfCDPK1 autophosphorylation while suppressing phosphorylation of competing substrates [#1]. Upon addition of a PfCDPK1 substrate, the kinase hyper-phosphorylates RKIP, driving RKIP dissociation and relieving inhibition so that PfCDPK1 can trans-phosphorylate downstream substrates — a substrate-competition regulatory switch operative during asexual schizogony [#4]. Beyond this PfCDPK1-regulatory role and its lipid-binding activity, no further cellular function of RKIP has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Establishing what kind of protein PF3D7_1219700 is: sequence determination placed it in the phosphatidylethanolamine-binding protein (PEBP) family, framing all subsequent lipid- and kinase-related hypotheses.\",\n      \"evidence\": \"Primary structure determination and sequence analysis in P. falciparum\",\n      \"pmids\": [\"7637711\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No functional assay; family assignment is sequence-based only\", \"No demonstration of lipid binding or any partner at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Testing whether RKIP has a functional relationship to a parasite kinase: in vitro assays showed it is a PfCDPK1 substrate and, more importantly, a modulator that boosts kinase autophosphorylation while dampening phosphorylation of other substrates.\",\n      \"evidence\": \"Recombinant protein expression, purification, and in vitro kinase assays with purified proteins\",\n      \"pmids\": [\"17123645\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction shown only in vitro, not in the parasite\", \"Structural basis of the regulatory effect unresolved\", \"Physiological consequence of the regulation not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Determining the structural framework of the protein: a 1.3 Å ortholog structure confirmed the PEBP fold but revealed a distinctive left-handed alpha-helical element beside the canonical phospholipid-binding site, defining a structurally distinct PEBP subfamily.\",\n      \"evidence\": \"X-ray crystallography (MAD, 1.3 Å) of the P. vivax RKIP ortholog\",\n      \"pmids\": [\"17329808\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structure is of the P. vivax ortholog, not the P. falciparum protein itself\", \"Functional role of the distinctive helical motif not tested by mutagenesis\", \"No ligand bound in the structure\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defining the lipid-binding activity implied by the PEBP fold: RKIP binds phosphatidic acid and phosphorylated phosphatidylinositols via conserved PEBP residues and a unique IKK motif, giving the family assignment concrete biochemical meaning.\",\n      \"evidence\": \"Lipid-binding assays, site-directed mutagenesis, and in silico docking in P. falciparum\",\n      \"pmids\": [\"39842334\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological lipid ligand in vivo not established\", \"Link between lipid binding and PfCDPK1 regulation not directly tested\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolving how RKIP regulates PfCDPK1 mechanistically and whether the interaction occurs in cells: RKIP interacts with PfCDPK1 in vitro and in the parasite, and substrate-driven hyper-phosphorylation of RKIP triggers its dissociation, establishing a substrate-competition switch that relieves inhibition of downstream substrate phosphorylation.\",\n      \"evidence\": \"ELISA, immunofluorescence, proximity biotinylation (BioID), and in vitro kinase assays in P. falciparum\",\n      \"pmids\": [\"39842334\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream PfCDPK1 substrates released by the switch not identified\", \"In-parasite functional consequence of RKIP loss not tested (no knockout/knockdown phenotype)\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RKIP is essential for asexual development and how its lipid binding is coupled to PfCDPK1 regulation in vivo remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genetic loss-of-function phenotype for RKIP reported\", \"Physiological trigger and biological output of the substrate-competition switch unknown\", \"Relationship between membrane lipid binding and kinase regulation untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008429\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005543\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0004860\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007165\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfCDPK1\"],\n    \"other_free_text\": [\n      \"PEBP-family protein with a PEBP domain harboring conserved lipid-binding residues and a distinctive IKK motif required for lipid interaction [#3].\",\n      \"Binds phosphatidic acid and phosphorylated phosphatidylinositols including PtdIns(3)P at physiological pH [#3].\",\n      \"Acts as both substrate and regulator of PfCDPK1: enhances kinase autophosphorylation and suppresses competing substrate phosphorylation [#1].\",\n      \"Substrate-competition switch: PfCDPK1 hyper-phosphorylation of RKIP drives dissociation and relieves inhibition [#4].\",\n      \"P. vivax ortholog structure (1.3 Å) shows PEBP fold with a distinctive left-handed alpha-helical element defining a distinct subfamily [#2].\",\n      \"Expressed throughout asexual schizogony, peaking in late schizonts [#5].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1219700","name":null,"product":"raf kinase inhibitor","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1434900","name":null,"product":"raf kinase inhibitor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1438900","name":null,"product":"raf kinase inhibitor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RKIP","evaluation":null}