{"gene":"PF3D7_1122800","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2007,"finding":"Disruption of the CDPK6 gene in P. berghei caused an increase in sporozoite cell traversal (CT) activity and reduced hepatocyte invasion, associated with a defect in CSP cleavage. CDPK6 was proposed to participate in signal transduction resulting in secretion of the protease that cleaves CSP upon sporozoite contact with highly sulfated HSPGs, mediating the switch from migratory to invasive behavior.","method":"Gene disruption (reverse genetics) in P. berghei with phenotypic readouts of cell traversal activity, hepatocyte invasion, and CSP cleavage","journal":"Cell host & microbe (cited in PMID:20951971 and PMID:33191548)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function genetic experiment with defined cellular phenotypes (CT, invasion, CSP cleavage) in a single study (Coppi et al., 2007), cited consistently across multiple independent reviews in this corpus but original data accessible only via citation","pmids":["20951971","33191548","32866196"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"Transcript levels of CDPK6 were significantly upregulated in P. falciparum parasites carrying a hypomorphic CDPK1 T145M gatekeeper mutation, suggesting that CDPK6 can compensate for reduced CDPK1 activity, potentially acting downstream of or in parallel to PKG.","method":"Quantitative transcriptomics (transcript level measurement by qPCR/RNA-seq) in CDPK1 T145M CRISPR/Cas9 mutant P. falciparum parasites","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab transcriptional upregulation data; no direct functional experiment on CDPK6 itself; compensatory role is inferred, not directly tested","pmids":["27923926"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Transcript levels of CDPK6 showed a modest but significant increase by qPCR in P. falciparum CDPK1 knockout parasites, corroborating transcriptional upregulation of CDPK6 as a compensatory response to loss of CDPK1.","method":"qPCR validation of RNA-seq data in CDPK1 knockout P. falciparum parasites generated by CRISPR/Cas9","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab transcriptional measurement; no direct functional experiment on CDPK6 itself; finding replicates the transcript-level observation from PMID:27923926 but still does not directly test CDPK6 function","pmids":["29311293"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"In a systematic epistasis screen of P. berghei kinases, deletion of CDPK6 in the hypomorphic PKG (PKGT619Q) / CDPK4-KO background did not produce a synthetic negative interaction on asexual blood-stage growth, indicating CDPK6 does not functionally complement CDPK4 in this context.","method":"Genetic epistasis screen — cdpk6 gene deletion introduced into PKGT619Q-3xHA/CDPK4-KO P. berghei background, asexual growth measured","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic epistasis experiment with defined double/triple mutant background and quantitative growth readout; single lab but rigorous genetic design","pmids":["30315162"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2006,"finding":"PfCDPK6 (PF11_0239/PF3D7_1122800) was identified as having an atypical domain organization compared to canonical CDPKs, with an unusually long amino acid sequence and variations in the assembly of EF-hands along the protein length, distinguishing it from CDPK1–5.","method":"Sequence/domain analysis referenced in review literature drawing on original structural/bioinformatic characterization","journal":"Computational and structural biotechnology journal","confidence":"Low","confidence_rationale":"Tier 4 / Weak — domain organization based on sequence/computational analysis as summarized in reviews; no direct experimental structural validation in the available abstracts","pmids":["34589185"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"PfCDPK6 protein was identified by yeast two-hybrid (Y2H) assays as associating with 11 partner proteins, including a putative Ndc80 protein (spindle checkpoint/kinetochore), a putative SRCAP chromatin-remodeling factor, PfBet1 (SNARE complex), a putative rhoptry-localized protein, a liver-stage antigen, a ubiquitin domain-containing protein, and five hypothetical proteins.","method":"Yeast two-hybrid (Y2H) interaction assays","journal":"BMC bioinformatics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Y2H data without reciprocal Co-IP or in vivo validation; single method, single study; functional significance of interactions not experimentally confirmed","pmids":["24267797"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CDPK6 (PF3D7_1122800) is a calcium-dependent protein kinase with atypical domain architecture that functions in P. berghei sporozoites to promote the switch from migratory cell traversal to productive hepatocyte invasion, acting through a signaling pathway that mediates CSP cleavage upon contact with highly sulfated heparan sulfate proteoglycans; in P. falciparum, CDPK6 transcript is upregulated as a compensatory response when CDPK1 activity is reduced, and the protein associates with multiple partners by yeast two-hybrid, but no direct enzymatic characterization or identification of in vivo substrates has been reported."},"narrative":{"mechanistic_narrative":"CDPK6 (PF3D7_1122800) is a calcium-dependent protein kinase implicated in the transition of Plasmodium sporozoites from a migratory to an invasive state. In P. berghei, gene disruption increases sporozoite cell traversal activity while reducing hepatocyte invasion and impairing CSP cleavage, placing CDPK6 in a signaling pathway that couples sporozoite contact with highly sulfated heparan sulfate proteoglycans to secretion of the CSP-cleaving protease and the switch to productive invasion [PMID:20951971, PMID:33191548, PMID:32866196]. In P. falciparum, CDPK6 transcript is upregulated when CDPK1 activity is genetically compromised, consistent with a compensatory role, though this is a transcript-level observation rather than a direct functional test [PMID:27923926, PMID:29311293]. CDPK6 has an atypical domain organization relative to CDPK1–5, with an unusually long sequence and variant EF-hand arrangement [PMID:34589185], and yeast two-hybrid screening links it to several candidate partners [PMID:24267797]. Beyond the P. berghei loss-of-function phenotype [PMID:20951971, PMID:33191548, PMID:32866196], no direct enzymatic characterization, in vivo substrate, or reciprocally validated interaction of CDPK6 has been established in the available corpus.","teleology":[{"year":2006,"claim":"Establishing that CDPK6 is structurally distinct from the other Plasmodium CDPKs framed it as a non-canonical member of the family whose function could not be assumed from CDPK1–5.","evidence":"Sequence/domain analysis of PfCDPK6 as summarized in review literature","pmids":["34589185"],"confidence":"Low","gaps":["based on computational/sequence analysis, not experimental structural validation","functional consequence of the atypical EF-hand arrangement unknown","no direct demonstration of calcium binding or kinase activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Loss-of-function genetics answered what CDPK6 does at the cellular level, showing it drives the sporozoite switch from cell traversal to hepatocyte invasion via a pathway required for CSP cleavage.","evidence":"cdpk6 gene disruption in P. berghei with readouts of cell traversal, hepatocyte invasion, and CSP cleavage","pmids":["20951971","33191548","32866196"],"confidence":"Medium","gaps":["the direct substrate of CDPK6 and the identity of the CSP-cleaving protease it regulates are not defined","molecular link between HSPG contact and CDPK6 activation not established","phenotype shown in P. berghei; not tested in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Y2H screening began to map candidate CDPK6 partners, offering hypotheses for its interaction network beyond the invasion phenotype.","evidence":"Yeast two-hybrid assays identifying 11 partner proteins for PfCDPK6","pmids":["24267797"],"confidence":"Low","gaps":["Y2H interactions not confirmed by reciprocal Co-IP or in vivo validation","functional significance of each partner unknown","diverse partner set (kinetochore, chromatin, SNARE, rhoptry) not reconciled into a coherent pathway"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Transcriptomic profiling in CDPK1-perturbed P. falciparum raised the possibility that CDPK6 acts as a compensatory kinase downstream of or parallel to PKG when CDPK1 is impaired.","evidence":"Transcript quantification (qPCR/RNA-seq) in P. falciparum CDPK1 T145M gatekeeper mutant and CDPK1 knockout parasites","pmids":["27923926","29311293"],"confidence":"Low","gaps":["compensation inferred from transcript upregulation, not directly tested functionally","no evidence CDPK6 protein activity increases or substitutes for CDPK1","position relative to PKG remains speculative"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"A genetic epistasis screen tested whether CDPK6 functionally overlaps with CDPK4 in blood-stage growth and found no synthetic interaction, constraining models of CDPK6 redundancy.","evidence":"cdpk6 deletion in a PKGT619Q/CDPK4-KO P. berghei background with asexual growth readout","pmids":["30315162"],"confidence":"Medium","gaps":["negative result does not define what CDPK6 does in blood stages","tested only for CDPK4 complementation, not other kinases","no biochemical activity assessed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The core enzymatic behavior of CDPK6 — its in vivo substrates, calcium dependence, and the mechanism linking HSPG sensing to CSP cleavage — remains uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["no direct kinase assay or substrate identification for CDPK6","the CSP-cleaving protease regulated downstream is not identified","Y2H partners lack orthogonal validation and pathway placement"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PUTATIVE NDC80 (Y2H, P. FALCIPARUM) [#5]","PUTATIVE SRCAP CHROMATIN-REMODELING FACTOR (Y2H) [#5]","PFBET1 SNARE PROTEIN (Y2H) [#5]","PUTATIVE RHOPTRY-LOCALIZED PROTEIN (Y2H) [#5]","LIVER-STAGE ANTIGEN (Y2H) [#5]","UBIQUITIN DOMAIN-CONTAINING PROTEIN (Y2H) [#5]"],"other_free_text":["In P. berghei, CDPK6 promotes the sporozoite switch from cell traversal to hepatocyte invasion and is required for CSP cleavage upon contact with highly sulfated HSPGs [#0].","In P. falciparum, CDPK6 transcript is upregulated when CDPK1 is genetically impaired, consistent with a compensatory role [#1, #2].","CDPK6 has an atypical domain organization with a long sequence and variant EF-hand arrangement relative to CDPK1–5 [#4].","CDPK6 deletion showed no synthetic interaction with CDPK4 loss in a PKG-hypomorphic P. berghei blood-stage background [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27923926","id":"PMC_27923926","title":"Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is Compensated in Plasmodium 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pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32866196","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CDPK6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33171706","id":"","title":"An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.","date":"2020","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/33171706","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CDPK6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32817103","id":"","title":"Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum 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microbe","url":"https://pubmed.ncbi.nlm.nih.gov/20951971","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CDPK6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":27137,"output_tokens":1847,"usd":0.054558,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6982,"output_tokens":2741,"usd":0.051717,"stage2_stop_reason":"end_turn"},"total_usd":0.106275,"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\": 2007,\n      \"finding\": \"Disruption of the CDPK6 gene in P. berghei caused an increase in sporozoite cell traversal (CT) activity and reduced hepatocyte invasion, associated with a defect in CSP cleavage. CDPK6 was proposed to participate in signal transduction resulting in secretion of the protease that cleaves CSP upon sporozoite contact with highly sulfated HSPGs, mediating the switch from migratory to invasive behavior.\",\n      \"method\": \"Gene disruption (reverse genetics) in P. berghei with phenotypic readouts of cell traversal activity, hepatocyte invasion, and CSP cleavage\",\n      \"journal\": \"Cell host & microbe (cited in PMID:20951971 and PMID:33191548)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function genetic experiment with defined cellular phenotypes (CT, invasion, CSP cleavage) in a single study (Coppi et al., 2007), cited consistently across multiple independent reviews in this corpus but original data accessible only via citation\",\n      \"pmids\": [\"20951971\", \"33191548\", \"32866196\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Transcript levels of CDPK6 were significantly upregulated in P. falciparum parasites carrying a hypomorphic CDPK1 T145M gatekeeper mutation, suggesting that CDPK6 can compensate for reduced CDPK1 activity, potentially acting downstream of or in parallel to PKG.\",\n      \"method\": \"Quantitative transcriptomics (transcript level measurement by qPCR/RNA-seq) in CDPK1 T145M CRISPR/Cas9 mutant P. falciparum parasites\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab transcriptional upregulation data; no direct functional experiment on CDPK6 itself; compensatory role is inferred, not directly tested\",\n      \"pmids\": [\"27923926\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Transcript levels of CDPK6 showed a modest but significant increase by qPCR in P. falciparum CDPK1 knockout parasites, corroborating transcriptional upregulation of CDPK6 as a compensatory response to loss of CDPK1.\",\n      \"method\": \"qPCR validation of RNA-seq data in CDPK1 knockout P. falciparum parasites generated by CRISPR/Cas9\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab transcriptional measurement; no direct functional experiment on CDPK6 itself; finding replicates the transcript-level observation from PMID:27923926 but still does not directly test CDPK6 function\",\n      \"pmids\": [\"29311293\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In a systematic epistasis screen of P. berghei kinases, deletion of CDPK6 in the hypomorphic PKG (PKGT619Q) / CDPK4-KO background did not produce a synthetic negative interaction on asexual blood-stage growth, indicating CDPK6 does not functionally complement CDPK4 in this context.\",\n      \"method\": \"Genetic epistasis screen — cdpk6 gene deletion introduced into PKGT619Q-3xHA/CDPK4-KO P. berghei background, asexual growth measured\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic epistasis experiment with defined double/triple mutant background and quantitative growth readout; single lab but rigorous genetic design\",\n      \"pmids\": [\"30315162\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"PfCDPK6 (PF11_0239/PF3D7_1122800) was identified as having an atypical domain organization compared to canonical CDPKs, with an unusually long amino acid sequence and variations in the assembly of EF-hands along the protein length, distinguishing it from CDPK1–5.\",\n      \"method\": \"Sequence/domain analysis referenced in review literature drawing on original structural/bioinformatic characterization\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — domain organization based on sequence/computational analysis as summarized in reviews; no direct experimental structural validation in the available abstracts\",\n      \"pmids\": [\"34589185\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PfCDPK6 protein was identified by yeast two-hybrid (Y2H) assays as associating with 11 partner proteins, including a putative Ndc80 protein (spindle checkpoint/kinetochore), a putative SRCAP chromatin-remodeling factor, PfBet1 (SNARE complex), a putative rhoptry-localized protein, a liver-stage antigen, a ubiquitin domain-containing protein, and five hypothetical proteins.\",\n      \"method\": \"Yeast two-hybrid (Y2H) interaction assays\",\n      \"journal\": \"BMC bioinformatics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Y2H data without reciprocal Co-IP or in vivo validation; single method, single study; functional significance of interactions not experimentally confirmed\",\n      \"pmids\": [\"24267797\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CDPK6 (PF3D7_1122800) is a calcium-dependent protein kinase with atypical domain architecture that functions in P. berghei sporozoites to promote the switch from migratory cell traversal to productive hepatocyte invasion, acting through a signaling pathway that mediates CSP cleavage upon contact with highly sulfated heparan sulfate proteoglycans; in P. falciparum, CDPK6 transcript is upregulated as a compensatory response when CDPK1 activity is reduced, and the protein associates with multiple partners by yeast two-hybrid, but no direct enzymatic characterization or identification of in vivo substrates has been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CDPK6 (PF3D7_1122800) is a calcium-dependent protein kinase implicated in the transition of Plasmodium sporozoites from a migratory to an invasive state. In P. berghei, gene disruption increases sporozoite cell traversal activity while reducing hepatocyte invasion and impairing CSP cleavage, placing CDPK6 in a signaling pathway that couples sporozoite contact with highly sulfated heparan sulfate proteoglycans to secretion of the CSP-cleaving protease and the switch to productive invasion [#0]. In P. falciparum, CDPK6 transcript is upregulated when CDPK1 activity is genetically compromised, consistent with a compensatory role, though this is a transcript-level observation rather than a direct functional test [#1, #2]. CDPK6 has an atypical domain organization relative to CDPK1\\u20135, with an unusually long sequence and variant EF-hand arrangement [#4], and yeast two-hybrid screening links it to several candidate partners [#5]. Beyond the P. berghei loss-of-function phenotype [#0], no direct enzymatic characterization, in vivo substrate, or reciprocally validated interaction of CDPK6 has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that CDPK6 is structurally distinct from the other Plasmodium CDPKs framed it as a non-canonical member of the family whose function could not be assumed from CDPK1\\u20135.\",\n      \"evidence\": \"Sequence/domain analysis of PfCDPK6 as summarized in review literature\",\n      \"pmids\": [\"34589185\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"based on computational/sequence analysis, not experimental structural validation\",\n        \"functional consequence of the atypical EF-hand arrangement unknown\",\n        \"no direct demonstration of calcium binding or kinase activity\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Loss-of-function genetics answered what CDPK6 does at the cellular level, showing it drives the sporozoite switch from cell traversal to hepatocyte invasion via a pathway required for CSP cleavage.\",\n      \"evidence\": \"cdpk6 gene disruption in P. berghei with readouts of cell traversal, hepatocyte invasion, and CSP cleavage\",\n      \"pmids\": [\"20951971\", \"33191548\", \"32866196\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"the direct substrate of CDPK6 and the identity of the CSP-cleaving protease it regulates are not defined\",\n        \"molecular link between HSPG contact and CDPK6 activation not established\",\n        \"phenotype shown in P. berghei; not tested in P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Y2H screening began to map candidate CDPK6 partners, offering hypotheses for its interaction network beyond the invasion phenotype.\",\n      \"evidence\": \"Yeast two-hybrid assays identifying 11 partner proteins for PfCDPK6\",\n      \"pmids\": [\"24267797\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Y2H interactions not confirmed by reciprocal Co-IP or in vivo validation\",\n        \"functional significance of each partner unknown\",\n        \"diverse partner set (kinetochore, chromatin, SNARE, rhoptry) not reconciled into a coherent pathway\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Transcriptomic profiling in CDPK1-perturbed P. falciparum raised the possibility that CDPK6 acts as a compensatory kinase downstream of or parallel to PKG when CDPK1 is impaired.\",\n      \"evidence\": \"Transcript quantification (qPCR/RNA-seq) in P. falciparum CDPK1 T145M gatekeeper mutant and CDPK1 knockout parasites\",\n      \"pmids\": [\"27923926\", \"29311293\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"compensation inferred from transcript upregulation, not directly tested functionally\",\n        \"no evidence CDPK6 protein activity increases or substitutes for CDPK1\",\n        \"position relative to PKG remains speculative\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A genetic epistasis screen tested whether CDPK6 functionally overlaps with CDPK4 in blood-stage growth and found no synthetic interaction, constraining models of CDPK6 redundancy.\",\n      \"evidence\": \"cdpk6 deletion in a PKGT619Q/CDPK4-KO P. berghei background with asexual growth readout\",\n      \"pmids\": [\"30315162\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"negative result does not define what CDPK6 does in blood stages\",\n        \"tested only for CDPK4 complementation, not other kinases\",\n        \"no biochemical activity assessed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core enzymatic behavior of CDPK6 \\u2014 its in vivo substrates, calcium dependence, and the mechanism linking HSPG sensing to CSP cleavage \\u2014 remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no direct kinase assay or substrate identification for CDPK6\",\n        \"the CSP-cleaving protease regulated downstream is not identified\",\n        \"Y2H partners lack orthogonal validation and pathway placement\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004683\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0007165\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Putative Ndc80 (Y2H, P. falciparum) [#5]\",\n      \"Putative SRCAP chromatin-remodeling factor (Y2H) [#5]\",\n      \"PfBet1 SNARE protein (Y2H) [#5]\",\n      \"Putative rhoptry-localized protein (Y2H) [#5]\",\n      \"Liver-stage antigen (Y2H) [#5]\",\n      \"Ubiquitin domain-containing protein (Y2H) [#5]\"\n    ],\n    \"other_free_text\": [\n      \"In P. berghei, CDPK6 promotes the sporozoite switch from cell traversal to hepatocyte invasion and is required for CSP cleavage upon contact with highly sulfated HSPGs [#0].\",\n      \"In P. falciparum, CDPK6 transcript is upregulated when CDPK1 is genetically impaired, consistent with a compensatory role [#1, #2].\",\n      \"CDPK6 has an atypical domain organization with a long sequence and variant EF-hand arrangement relative to CDPK1\\u20135 [#4].\",\n      \"CDPK6 deletion showed no synthetic interaction with CDPK4 loss in a PKG-hypomorphic P. berghei blood-stage background [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1122800","name":null,"product":"calcium-dependent protein kinase 6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0925500","name":null,"product":"calcium-dependent protein kinase 6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0920600","name":null,"product":"calcium-dependent protein kinase 6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CDPK6","evaluation":null}