{"gene":"PF3D7_0719500","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2018,"finding":"CDC50A binds to and stabilizes guanylate cyclase β (GCβ) during ookinete development in Plasmodium yoelii, acting as a co-factor for the P4-ATPase-like domain of GCβ.","method":"Real-time imaging and co-factor binding assay; genetic analysis showing both P4-ATPase-like and guanylate cyclase domains of GCβ are required for polarization and ookinete gliding","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, binding interaction demonstrated in vivo with functional consequence (ookinete gliding), but binding assay details are from abstract only","pmids":["30146157"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2018,"finding":"The GCβ/CDC50A complex is anchored at the 'ookinete extrados site' (OES) of the parasite plasma membrane by inner membrane complex protein ISP1, and this polarization is required for initiation of ookinete gliding motility.","method":"Real-time fluorescence imaging of GCβ translocation; genetic screening of inner membrane complex proteins identifying ISP1 as anchor","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging with functional consequence (gliding motility), single lab, multiple observations supporting spatial-temporal model","pmids":["30146157"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2022,"finding":"CDC50A is NOT expressed in the clinically important asexual blood stages of Plasmodium falciparum; conditional gene disruption and gene tagging experiments showed that CDC50B and CDC50C (but not CDC50A) are expressed in intraerythrocytic stages, and CDC50A is not a binding partner of GCα in blood stages.","method":"Gene tagging and conditional gene disruption in P. falciparum blood stages","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genetic approach with gene tagging and conditional disruption, single lab, negative result for CDC50A expression/function in blood stages","pmids":["35862778"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Recombinantly produced Plasmodium chabaudi ATP2 (PcATP2) associates with CDC50A (PcCdc50A) in addition to PcCdc50B, as demonstrated with purified proteins; however, the ATPase activity (lipid-stimulated ATP hydrolysis with phosphatidylserine, phosphatidylethanolamine, and upregulation by phosphatidylinositol 4-phosphate) was demonstrated for the PcATP2/PcCdc50B complex specifically.","method":"Recombinant protein production, co-purification, and in vitro ATPase activity assay","journal":"Emerging microbes & infections","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-purification demonstrates association of CDC50A with PcATP2, single lab, but functional ATPase characterization was only shown for the CDC50B complex, not for the CDC50A complex","pmids":["33372863"],"is_preprint":false,"attribution":[{"species":"Plasmodium chabaudi","strain":""}]}],"current_model":"CDC50A (PF3D7_0719500) functions as a co-factor that binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β (GCβ) in Plasmodium ookinetes, where the GCβ/CDC50A complex is anchored at the ookinete extrados site by ISP1 to initiate cGMP-dependent gliding motility; in P. falciparum asexual blood stages CDC50A is not detectably expressed and does not serve as the primary CDC50 partner for blood-stage P4-ATPases (that role being filled by CDC50B and CDC50C), though recombinant P. chabaudi ATP2 can associate with CDC50A in vitro."},"narrative":{"mechanistic_narrative":"CDC50A (PF3D7_0719500) is a P4-ATPase co-factor that operates in the transmission stages of the malaria parasite, where it binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β (GCβ) during ookinete development in Plasmodium yoelii [PMID:30146157]. The resulting GCβ/CDC50A complex is polarized to the ookinete extrados site of the plasma membrane by the inner membrane complex protein ISP1, and this spatial anchoring is required to initiate cGMP-dependent ookinete gliding motility [PMID:30146157]. CDC50A's role is stage-restricted: in Plasmodium falciparum asexual blood stages it is not detectably expressed and does not partner GCα, with CDC50B and CDC50C instead filling the blood-stage CDC50 role [PMID:35862778]. A distinct P4-ATPase association is seen in vitro, where recombinant Plasmodium chabaudi ATP2 co-purifies with CDC50A [PMID:33372863]. Beyond these findings, the biochemical activity of CDC50A-containing complexes has not been directly characterized in the available corpus.","teleology":[{"year":2018,"claim":"Established that CDC50A serves as the co-factor that binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β, linking a CDC50 protein to cGMP signaling machinery rather than to a standalone lipid flippase.","evidence":"Real-time imaging and co-factor binding assay with genetic dissection of GCβ domains in Plasmodium yoelii ookinetes","pmids":["30146157"],"confidence":"Medium","gaps":["Binding assay details available only from abstract","Whether CDC50A contributes catalytic or purely structural stabilization is not resolved","No structural model of the GCβ/CDC50A interface"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2018,"claim":"Showed how the GCβ/CDC50A complex is spatially deployed, identifying ISP1-dependent anchoring at the ookinete extrados site as the trigger for initiating gliding motility.","evidence":"Live fluorescence imaging of GCβ translocation and genetic screening of inner membrane complex proteins in Plasmodium yoelii","pmids":["30146157"],"confidence":"Medium","gaps":["Molecular basis of the ISP1–complex interaction unknown","Whether CDC50A itself contacts ISP1 or only through GCβ is not defined"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2021,"claim":"Tested whether CDC50A can partner a canonical P4-ATPase, showing recombinant P. chabaudi ATP2 associates with CDC50A in vitro, though catalytic activity was demonstrated only for the CDC50B-containing complex.","evidence":"Recombinant protein production, co-purification, and in vitro ATPase assay in Plasmodium chabaudi proteins","pmids":["33372863"],"confidence":"Low","gaps":["ATPase/flippase activity of the ATP2/CDC50A complex was not measured","In vitro association may not reflect an in vivo partnership","Physiological relevance of the ATP2–CDC50A pairing unestablished"],"attribution":[{"species":"Plasmodium chabaudi","strain":""}]},{"year":2022,"claim":"Defined the stage-specificity of CDC50A by showing it is not expressed in P. falciparum asexual blood stages and is not the GCα partner there, distinguishing its role from the blood-stage co-factors CDC50B and CDC50C.","evidence":"Gene tagging and conditional gene disruption in P. falciparum blood stages","pmids":["35862778"],"confidence":"Medium","gaps":["Does not address CDC50A function in P. falciparum transmission stages","Negative expression result does not rule out low-level or conditional expression"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic biochemical activity of any CDC50A-containing complex and its precise contribution (structural vs catalytic) to GCβ function remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct measurement of activity for a CDC50A-containing complex","No structural characterization of CDC50A","Function in P. falciparum sexual/mosquito stages uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GCβ/CDC50A complex (guanylate cyclase β co-factor complex)","PcATP2/CDC50A complex (in vitro, Plasmodium chabaudi)"],"partners":["GUANYLATE CYCLASE Β (GCΒ)","ISP1 (INNER MEMBRANE COMPLEX PROTEIN, ANCHOR)","PCATP2 (P. CHABAUDI P4-ATPASE, IN VITRO)"],"other_free_text":["CDC50A stabilizes the P4-ATPase-like domain of GCβ during ookinete development in P. yoelii.","GCβ/CDC50A is polarized to the ookinete extrados site by ISP1 to initiate cGMP-dependent gliding motility.","CDC50A is not detectably expressed in P. falciparum asexual blood stages and is not the GCα partner there; CDC50B and CDC50C fill the blood-stage CDC50 role.","Catalytic ATPase activity was demonstrated for the PcATP2/CDC50B complex, not for the CDC50A-containing complex."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30146157","id":"PMC_30146157","title":"ISP1-Anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility.","date":"2018","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/30146157","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CDC50A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35862778","id":"PMC_35862778","title":"CDC50 Orthologues in Plasmodium falciparum Have Distinct Roles in Merozoite Egress and Trophozoite Maturation.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35862778","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CDC50A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33372863","id":"PMC_33372863","title":"ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit.","date":"2021","source":"Emerging microbes & infections","url":"https://pubmed.ncbi.nlm.nih.gov/33372863","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PcCDC50A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4590,"output_tokens":1236,"usd":0.016155,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6112,"output_tokens":2318,"usd":0.044255,"stage2_stop_reason":"end_turn"},"total_usd":0.06041,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"CDC50A binds to and stabilizes guanylate cyclase β (GCβ) during ookinete development in Plasmodium yoelii, acting as a co-factor for the P4-ATPase-like domain of GCβ.\",\n      \"method\": \"Real-time imaging and co-factor binding assay; genetic analysis showing both P4-ATPase-like and guanylate cyclase domains of GCβ are required for polarization and ookinete gliding\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, binding interaction demonstrated in vivo with functional consequence (ookinete gliding), but binding assay details are from abstract only\",\n      \"pmids\": [\"30146157\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The GCβ/CDC50A complex is anchored at the 'ookinete extrados site' (OES) of the parasite plasma membrane by inner membrane complex protein ISP1, and this polarization is required for initiation of ookinete gliding motility.\",\n      \"method\": \"Real-time fluorescence imaging of GCβ translocation; genetic screening of inner membrane complex proteins identifying ISP1 as anchor\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging with functional consequence (gliding motility), single lab, multiple observations supporting spatial-temporal model\",\n      \"pmids\": [\"30146157\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CDC50A is NOT expressed in the clinically important asexual blood stages of Plasmodium falciparum; conditional gene disruption and gene tagging experiments showed that CDC50B and CDC50C (but not CDC50A) are expressed in intraerythrocytic stages, and CDC50A is not a binding partner of GCα in blood stages.\",\n      \"method\": \"Gene tagging and conditional gene disruption in P. falciparum blood stages\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genetic approach with gene tagging and conditional disruption, single lab, negative result for CDC50A expression/function in blood stages\",\n      \"pmids\": [\"35862778\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Recombinantly produced Plasmodium chabaudi ATP2 (PcATP2) associates with CDC50A (PcCdc50A) in addition to PcCdc50B, as demonstrated with purified proteins; however, the ATPase activity (lipid-stimulated ATP hydrolysis with phosphatidylserine, phosphatidylethanolamine, and upregulation by phosphatidylinositol 4-phosphate) was demonstrated for the PcATP2/PcCdc50B complex specifically.\",\n      \"method\": \"Recombinant protein production, co-purification, and in vitro ATPase activity assay\",\n      \"journal\": \"Emerging microbes & infections\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-purification demonstrates association of CDC50A with PcATP2, single lab, but functional ATPase characterization was only shown for the CDC50B complex, not for the CDC50A complex\",\n      \"pmids\": [\"33372863\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium chabaudi\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CDC50A (PF3D7_0719500) functions as a co-factor that binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β (GCβ) in Plasmodium ookinetes, where the GCβ/CDC50A complex is anchored at the ookinete extrados site by ISP1 to initiate cGMP-dependent gliding motility; in P. falciparum asexual blood stages CDC50A is not detectably expressed and does not serve as the primary CDC50 partner for blood-stage P4-ATPases (that role being filled by CDC50B and CDC50C), though recombinant P. chabaudi ATP2 can associate with CDC50A in vitro.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CDC50A (PF3D7_0719500) is a P4-ATPase co-factor that operates in the transmission stages of the malaria parasite, where it binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β (GCβ) during ookinete development in Plasmodium yoelii [#0]. The resulting GCβ/CDC50A complex is polarized to the ookinete extrados site of the plasma membrane by the inner membrane complex protein ISP1, and this spatial anchoring is required to initiate cGMP-dependent ookinete gliding motility [#1]. CDC50A's role is stage-restricted: in Plasmodium falciparum asexual blood stages it is not detectably expressed and does not partner GCα, with CDC50B and CDC50C instead filling the blood-stage CDC50 role [#2]. A distinct P4-ATPase association is seen in vitro, where recombinant Plasmodium chabaudi ATP2 co-purifies with CDC50A [#3]. Beyond these findings, the biochemical activity of CDC50A-containing complexes has not been directly characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established that CDC50A serves as the co-factor that binds and stabilizes the P4-ATPase-like domain of guanylate cyclase β, linking a CDC50 protein to cGMP signaling machinery rather than to a standalone lipid flippase.\",\n      \"evidence\": \"Real-time imaging and co-factor binding assay with genetic dissection of GCβ domains in Plasmodium yoelii ookinetes\",\n      \"pmids\": [\"30146157\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding assay details available only from abstract\", \"Whether CDC50A contributes catalytic or purely structural stabilization is not resolved\", \"No structural model of the GCβ/CDC50A interface\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed how the GCβ/CDC50A complex is spatially deployed, identifying ISP1-dependent anchoring at the ookinete extrados site as the trigger for initiating gliding motility.\",\n      \"evidence\": \"Live fluorescence imaging of GCβ translocation and genetic screening of inner membrane complex proteins in Plasmodium yoelii\",\n      \"pmids\": [\"30146157\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the ISP1–complex interaction unknown\", \"Whether CDC50A itself contacts ISP1 or only through GCβ is not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Tested whether CDC50A can partner a canonical P4-ATPase, showing recombinant P. chabaudi ATP2 associates with CDC50A in vitro, though catalytic activity was demonstrated only for the CDC50B-containing complex.\",\n      \"evidence\": \"Recombinant protein production, co-purification, and in vitro ATPase assay in Plasmodium chabaudi proteins\",\n      \"pmids\": [\"33372863\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"ATPase/flippase activity of the ATP2/CDC50A complex was not measured\", \"In vitro association may not reflect an in vivo partnership\", \"Physiological relevance of the ATP2–CDC50A pairing unestablished\"],\n      \"attribution\": [{\"species\": \"Plasmodium chabaudi\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined the stage-specificity of CDC50A by showing it is not expressed in P. falciparum asexual blood stages and is not the GCα partner there, distinguishing its role from the blood-stage co-factors CDC50B and CDC50C.\",\n      \"evidence\": \"Gene tagging and conditional gene disruption in P. falciparum blood stages\",\n      \"pmids\": [\"35862778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address CDC50A function in P. falciparum transmission stages\", \"Negative expression result does not rule out low-level or conditional expression\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemical activity of any CDC50A-containing complex and its precise contribution (structural vs catalytic) to GCβ function remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct measurement of activity for a CDC50A-containing complex\", \"No structural characterization of CDC50A\", \"Function in P. falciparum sexual/mosquito stages uncharacterized\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071502\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0071973\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"GCβ/CDC50A complex (guanylate cyclase β co-factor complex)\",\n      \"PcATP2/CDC50A complex (in vitro, Plasmodium chabaudi)\"\n    ],\n    \"partners\": [\n      \"Guanylate cyclase β (GCβ)\",\n      \"ISP1 (inner membrane complex protein, anchor)\",\n      \"PcATP2 (P. chabaudi P4-ATPase, in vitro)\"\n    ],\n    \"other_free_text\": [\n      \"CDC50A stabilizes the P4-ATPase-like domain of GCβ during ookinete development in P. yoelii.\",\n      \"GCβ/CDC50A is polarized to the ookinete extrados site by ISP1 to initiate cGMP-dependent gliding motility.\",\n      \"CDC50A is not detectably expressed in P. falciparum asexual blood stages and is not the GCα partner there; CDC50B and CDC50C fill the blood-stage CDC50 role.\",\n      \"Catalytic ATPase activity was demonstrated for the PcATP2/CDC50B complex, not for the CDC50A-containing complex.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0719500","name":null,"product":"cell division control protein CDC50A","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0617000","name":null,"product":"LEM3/CDC50 family protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0314900","name":null,"product":"cell division control protein CDC50A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CDC50A","evaluation":null}