{"gene":"PF3D7_1451700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2005,"finding":"CNB (calcineurin regulatory subunit B) harbors mutations in functionally significant amino acid residues in cyclosporin A-resistant P. falciparum clones, and the calcineurin complex (CnA/CnB) associates with Hsp90 in vivo; geldanamycin disrupts this association while CsA does not. Mutations in CnB along with CnA correlate with CsA-resistant phosphatase activity in vitro, indicating CNB's role in regulating calcineurin catalytic function.","method":"In vivo co-immunoprecipitation (calcineurin–Hsp90 association); sequencing of CsA-resistant clones for mutations in CnA and CnB; in vitro protein phosphatase activity assay with CsA","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP for Hsp90 association, in vitro phosphatase assay, and mutant analysis in a single lab with two orthogonal methods","pmids":["15811524"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"The full-length calcineurin complex (PP2B) including its regulatory subunit (CNB, which carries the calmodulin-binding domain needed for Ca²⁺ stimulation) undergoes rapid, specific in vivo proteolytic processing in P. falciparum, generating a constitutively active catalytic core that is less responsive or unresponsive to Ca²⁺, distinct from the Ca²⁺-dependent full-length complex.","method":"Biochemical fractionation and in vitro phosphatase activity assays comparing full-length vs. processed core forms; in vivo processing demonstrated in parasite lysates","journal":"BMC molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical in vitro assay plus in vivo fractionation, single lab, two orthogonal methods","pmids":["15230980"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"The calcineurin complex (PfCN), of which CNB is the regulatory subunit, is an essential regulator of Ca²⁺-dependent microneme exocytosis in P. falciparum merozoites: calcineurin activity increases upon exposure to low K⁺ environment, and its inhibition (with FK506 or cyclosporin A) blocks dephosphorylation and depolymerization of apical actin, thereby inhibiting secretion of PfAMA-1 from micronemes.","method":"Calcineurin activity assay in merozoites under low K⁺ conditions; pharmacological inhibition with FK506/CsA; immunofluorescence and biochemical assay of actin polymerization state; microneme secretion assay (PfAMA-1 surface exposure)","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (activity assay, inhibitor experiments, actin state readout, secretion assay) in single lab; CNB as regulatory subunit is implicated through the complex but not individually mutagenized","pmids":["23910910"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The calcineurin complex (of which CNB is the regulatory subunit) critically regulates and stabilizes attachment of extracellular P. falciparum merozoites to host erythrocytes before intracellular entry; this calcineurin-mediated attachment is strongly associated with host receptors required for host cell recognition and is mechanistically distinct from a second, receptor-independent mode of host-parasite adhesion.","method":"Reverse-genetic and chemical-genetic approaches in P. falciparum; invasion assays measuring attachment and entry; receptor-dependent vs. receptor-independent invasion pathway dissection","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reverse-genetic and chemical-genetic approaches with multiple pathway readouts, single study; CNB implicated as part of the calcineurin complex but not individually manipulated","pmids":["26118996"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CNB (PF3D7_1451700), the regulatory subunit of P. falciparum calcineurin (PP2B), contributes to calcineurin complex function by providing Ca²⁺/calmodulin-dependent regulation; the intact complex associates with Hsp90 in vivo, undergoes proteolytic processing to generate a constitutively active Ca²⁺-independent catalytic core, and is required for receptor-dependent erythrocyte attachment and Ca²⁺-triggered microneme exocytosis (via actin dephosphorylation/depolymerization) during invasion — with mutations in CNB conferring cyclosporin A resistance."},"narrative":{"mechanistic_narrative":"CNB (PF3D7_1451700) is the regulatory subunit of P. falciparum calcineurin (PP2B), a Ca²⁺/calmodulin-dependent serine/threonine phosphatase in which CNB carries the calmodulin-binding domain required for Ca²⁺ stimulation of the catalytic subunit [PMID:15230980]. Mutations in CNB (together with the catalytic CnA subunit) are found in cyclosporin A-resistant parasite clones and correlate with CsA-resistant phosphatase activity in vitro, establishing that CNB participates directly in setting the catalytic properties of the enzyme; the intact CnA/CnB complex also associates with Hsp90 in vivo in a geldanamycin-sensitive, CsA-insensitive manner [PMID:15811524]. The full-length complex undergoes rapid, specific in vivo proteolytic processing to yield a constitutively active catalytic core that is largely uncoupled from Ca²⁺ regulation, distinguishing it from the Ca²⁺-dependent full-length holoenzyme [PMID:15230980]. Functionally, the calcineurin complex is required during erythrocyte invasion: it drives Ca²⁺-dependent microneme exocytosis in merozoites — activity rises upon low-K⁺ exposure and its inhibition blocks dephosphorylation and depolymerization of apical actin and secretion of PfAMA-1 [PMID:23910910] — and it stabilizes receptor-dependent attachment of extracellular merozoites to host erythrocytes prior to entry [PMID:26118996]. In these invasion studies CNB is implicated through its membership in the calcineurin complex rather than by individual manipulation; beyond its role as the regulatory subunit and the CsA-resistance mutations, no CNB-specific mechanism has been characterized in the available corpus.","teleology":[{"year":2004,"claim":"It was unknown how P. falciparum calcineurin activity is controlled relative to its Ca²⁺-dependence; this work showed the holoenzyme (bearing the Ca²⁺/calmodulin-responsive CNB subunit) is proteolytically processed in vivo into a constitutively active, Ca²⁺-uncoupled core, establishing a regulatory switch for the enzyme.","evidence":"Biochemical fractionation and in vitro phosphatase assays comparing full-length vs. processed forms, with in vivo processing shown in parasite lysates","pmids":["15230980"],"confidence":"Medium","gaps":["The protease responsible for processing and the cleavage site were not identified","CNB's individual fate during processing (retained vs. removed) was not resolved","Physiological trigger and timing of processing during the life cycle not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"It was unknown whether CNB contributes to calcineurin's drug sensitivity and higher-order assembly; identifying CNB mutations in CsA-resistant clones and Hsp90 association of the complex placed CNB within a chaperoned, drug-targetable phosphatase whose catalytic properties depend on its regulatory subunit.","evidence":"In vivo co-immunoprecipitation of calcineurin with Hsp90, sequencing of CsA-resistant clones for CnA/CnB mutations, and in vitro phosphatase assays with CsA","pmids":["15811524"],"confidence":"Medium","gaps":["Whether the CNB mutations alone (versus CnA mutations) confer CsA resistance was not separated","Structural basis of how CNB mutations alter catalytic/drug-binding properties not determined","Functional consequence of the Hsp90 association for CNB was not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"It was unknown what invasion step calcineurin controls; this work showed the complex is an essential regulator of Ca²⁺-dependent microneme exocytosis, acting through apical actin dephosphorylation/depolymerization to enable PfAMA-1 secretion.","evidence":"Calcineurin activity assays under low-K⁺ conditions, FK506/CsA inhibition, actin polymerization readouts, and microneme secretion (PfAMA-1 surface exposure) assays in merozoites","pmids":["23910910"],"confidence":"Medium","gaps":["CNB was implicated only through the complex, not individually mutagenized or depleted","Direct actin/actin-regulator dephosphorylation substrate of calcineurin not identified","How CNB-mediated Ca²⁺ sensing is coupled to microneme secretion mechanistically unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"It was unknown whether calcineurin acts at the attachment step of invasion; reverse- and chemical-genetic dissection showed the complex stabilizes receptor-dependent merozoite attachment to erythrocytes, distinct from a receptor-independent adhesion mode.","evidence":"Reverse-genetic and chemical-genetic approaches with invasion/attachment assays dissecting receptor-dependent vs. receptor-independent pathways","pmids":["26118996"],"confidence":"Medium","gaps":["CNB was implicated as part of the calcineurin complex but not individually manipulated","Molecular substrates linking calcineurin activity to attachment stabilization not identified","Relationship between the attachment role and the microneme secretion role not integrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what CNB does independent of the calcineurin holoenzyme — no CNB-specific substrate, structural model, or individually resolved loss-of-function phenotype has been established in this corpus.","evidence":"No discovery isolates CNB function apart from its role as the regulatory subunit of the calcineurin complex","pmids":[],"confidence":"Low","gaps":["No CNB-only genetic depletion or complementation reported","Structural basis of CNB Ca²⁺/calmodulin sensing in P. falciparum not defined","CNB interactome beyond CnA and Hsp90-associated complex uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Calcineurin (PP2B) complex: CnA catalytic subunit + CNB regulatory subunit","Calcineurin–Hsp90 in vivo association"],"partners":["CNA (CALCINEURIN CATALYTIC SUBUNIT)","HSP90 (ASSOCIATION WITH THE CALCINEURIN COMPLEX)","CALMODULIN (BINDS VIA THE CNB REGULATORY SUBUNIT FOR CA²⁺ STIMULATION)"],"other_free_text":["CNB mutations found in cyclosporin A-resistant P. falciparum clones and correlate with CsA-resistant phosphatase activity in vitro","Full-length calcineurin holoenzyme undergoes rapid in vivo proteolytic processing to a constitutively active, Ca²⁺-uncoupled catalytic core","Calcineurin activity required for Ca²⁺-dependent microneme exocytosis (PfAMA-1 secretion) via apical actin dephosphorylation/depolymerization","Calcineurin stabilizes receptor-dependent merozoite–erythrocyte attachment during invasion","In invasion studies CNB is implicated through complex membership rather than by individual genetic manipulation"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26118996","id":"PMC_26118996","title":"Parasite Calcineurin Regulates Host Cell Recognition and Attachment by Apicomplexans.","date":"2015","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/26118996","citation_count":72,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15811524","id":"PMC_15811524","title":"Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15811524","citation_count":52,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CNB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15230980","id":"PMC_15230980","title":"Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics.","date":"2004","source":"BMC molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15230980","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23910910","id":"PMC_23910910","title":"Role of calcineurin and actin dynamics in regulated secretion of microneme proteins in Plasmodium falciparum merozoites during erythrocyte invasion.","date":"2013","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23910910","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4828,"output_tokens":1428,"usd":0.017952,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6414,"output_tokens":3215,"usd":0.056223,"stage2_stop_reason":"end_turn"},"total_usd":0.074175,"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\": 2005,\n      \"finding\": \"CNB (calcineurin regulatory subunit B) harbors mutations in functionally significant amino acid residues in cyclosporin A-resistant P. falciparum clones, and the calcineurin complex (CnA/CnB) associates with Hsp90 in vivo; geldanamycin disrupts this association while CsA does not. Mutations in CnB along with CnA correlate with CsA-resistant phosphatase activity in vitro, indicating CNB's role in regulating calcineurin catalytic function.\",\n      \"method\": \"In vivo co-immunoprecipitation (calcineurin–Hsp90 association); sequencing of CsA-resistant clones for mutations in CnA and CnB; in vitro protein phosphatase activity assay with CsA\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP for Hsp90 association, in vitro phosphatase assay, and mutant analysis in a single lab with two orthogonal methods\",\n      \"pmids\": [\"15811524\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The full-length calcineurin complex (PP2B) including its regulatory subunit (CNB, which carries the calmodulin-binding domain needed for Ca²⁺ stimulation) undergoes rapid, specific in vivo proteolytic processing in P. falciparum, generating a constitutively active catalytic core that is less responsive or unresponsive to Ca²⁺, distinct from the Ca²⁺-dependent full-length complex.\",\n      \"method\": \"Biochemical fractionation and in vitro phosphatase activity assays comparing full-length vs. processed core forms; in vivo processing demonstrated in parasite lysates\",\n      \"journal\": \"BMC molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical in vitro assay plus in vivo fractionation, single lab, two orthogonal methods\",\n      \"pmids\": [\"15230980\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The calcineurin complex (PfCN), of which CNB is the regulatory subunit, is an essential regulator of Ca²⁺-dependent microneme exocytosis in P. falciparum merozoites: calcineurin activity increases upon exposure to low K⁺ environment, and its inhibition (with FK506 or cyclosporin A) blocks dephosphorylation and depolymerization of apical actin, thereby inhibiting secretion of PfAMA-1 from micronemes.\",\n      \"method\": \"Calcineurin activity assay in merozoites under low K⁺ conditions; pharmacological inhibition with FK506/CsA; immunofluorescence and biochemical assay of actin polymerization state; microneme secretion assay (PfAMA-1 surface exposure)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (activity assay, inhibitor experiments, actin state readout, secretion assay) in single lab; CNB as regulatory subunit is implicated through the complex but not individually mutagenized\",\n      \"pmids\": [\"23910910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The calcineurin complex (of which CNB is the regulatory subunit) critically regulates and stabilizes attachment of extracellular P. falciparum merozoites to host erythrocytes before intracellular entry; this calcineurin-mediated attachment is strongly associated with host receptors required for host cell recognition and is mechanistically distinct from a second, receptor-independent mode of host-parasite adhesion.\",\n      \"method\": \"Reverse-genetic and chemical-genetic approaches in P. falciparum; invasion assays measuring attachment and entry; receptor-dependent vs. receptor-independent invasion pathway dissection\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reverse-genetic and chemical-genetic approaches with multiple pathway readouts, single study; CNB implicated as part of the calcineurin complex but not individually manipulated\",\n      \"pmids\": [\"26118996\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CNB (PF3D7_1451700), the regulatory subunit of P. falciparum calcineurin (PP2B), contributes to calcineurin complex function by providing Ca²⁺/calmodulin-dependent regulation; the intact complex associates with Hsp90 in vivo, undergoes proteolytic processing to generate a constitutively active Ca²⁺-independent catalytic core, and is required for receptor-dependent erythrocyte attachment and Ca²⁺-triggered microneme exocytosis (via actin dephosphorylation/depolymerization) during invasion — with mutations in CNB conferring cyclosporin A resistance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CNB (PF3D7_1451700) is the regulatory subunit of P. falciparum calcineurin (PP2B), a Ca²⁺/calmodulin-dependent serine/threonine phosphatase in which CNB carries the calmodulin-binding domain required for Ca²⁺ stimulation of the catalytic subunit [#1]. Mutations in CNB (together with the catalytic CnA subunit) are found in cyclosporin A-resistant parasite clones and correlate with CsA-resistant phosphatase activity in vitro, establishing that CNB participates directly in setting the catalytic properties of the enzyme; the intact CnA/CnB complex also associates with Hsp90 in vivo in a geldanamycin-sensitive, CsA-insensitive manner [#0]. The full-length complex undergoes rapid, specific in vivo proteolytic processing to yield a constitutively active catalytic core that is largely uncoupled from Ca²⁺ regulation, distinguishing it from the Ca²⁺-dependent full-length holoenzyme [#1]. Functionally, the calcineurin complex is required during erythrocyte invasion: it drives Ca²⁺-dependent microneme exocytosis in merozoites — activity rises upon low-K⁺ exposure and its inhibition blocks dephosphorylation and depolymerization of apical actin and secretion of PfAMA-1 [#2] — and it stabilizes receptor-dependent attachment of extracellular merozoites to host erythrocytes prior to entry [#3]. In these invasion studies CNB is implicated through its membership in the calcineurin complex rather than by individual manipulation; beyond its role as the regulatory subunit and the CsA-resistance mutations, no CNB-specific mechanism has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"It was unknown how P. falciparum calcineurin activity is controlled relative to its Ca²⁺-dependence; this work showed the holoenzyme (bearing the Ca²⁺/calmodulin-responsive CNB subunit) is proteolytically processed in vivo into a constitutively active, Ca²⁺-uncoupled core, establishing a regulatory switch for the enzyme.\",\n      \"evidence\": \"Biochemical fractionation and in vitro phosphatase assays comparing full-length vs. processed forms, with in vivo processing shown in parasite lysates\",\n      \"pmids\": [\n        \"15230980\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The protease responsible for processing and the cleavage site were not identified\",\n        \"CNB's individual fate during processing (retained vs. removed) was not resolved\",\n        \"Physiological trigger and timing of processing during the life cycle not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"It was unknown whether CNB contributes to calcineurin's drug sensitivity and higher-order assembly; identifying CNB mutations in CsA-resistant clones and Hsp90 association of the complex placed CNB within a chaperoned, drug-targetable phosphatase whose catalytic properties depend on its regulatory subunit.\",\n      \"evidence\": \"In vivo co-immunoprecipitation of calcineurin with Hsp90, sequencing of CsA-resistant clones for CnA/CnB mutations, and in vitro phosphatase assays with CsA\",\n      \"pmids\": [\n        \"15811524\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the CNB mutations alone (versus CnA mutations) confer CsA resistance was not separated\",\n        \"Structural basis of how CNB mutations alter catalytic/drug-binding properties not determined\",\n        \"Functional consequence of the Hsp90 association for CNB was not tested\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"It was unknown what invasion step calcineurin controls; this work showed the complex is an essential regulator of Ca²⁺-dependent microneme exocytosis, acting through apical actin dephosphorylation/depolymerization to enable PfAMA-1 secretion.\",\n      \"evidence\": \"Calcineurin activity assays under low-K⁺ conditions, FK506/CsA inhibition, actin polymerization readouts, and microneme secretion (PfAMA-1 surface exposure) assays in merozoites\",\n      \"pmids\": [\n        \"23910910\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"CNB was implicated only through the complex, not individually mutagenized or depleted\",\n        \"Direct actin/actin-regulator dephosphorylation substrate of calcineurin not identified\",\n        \"How CNB-mediated Ca²⁺ sensing is coupled to microneme secretion mechanistically unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unknown whether calcineurin acts at the attachment step of invasion; reverse- and chemical-genetic dissection showed the complex stabilizes receptor-dependent merozoite attachment to erythrocytes, distinct from a receptor-independent adhesion mode.\",\n      \"evidence\": \"Reverse-genetic and chemical-genetic approaches with invasion/attachment assays dissecting receptor-dependent vs. receptor-independent pathways\",\n      \"pmids\": [\n        \"26118996\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"CNB was implicated as part of the calcineurin complex but not individually manipulated\",\n        \"Molecular substrates linking calcineurin activity to attachment stabilization not identified\",\n        \"Relationship between the attachment role and the microneme secretion role not integrated\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what CNB does independent of the calcineurin holoenzyme — no CNB-specific substrate, structural model, or individually resolved loss-of-function phenotype has been established in this corpus.\",\n      \"evidence\": \"No discovery isolates CNB function apart from its role as the regulatory subunit of the calcineurin complex\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No CNB-only genetic depletion or complementation reported\",\n        \"Structural basis of CNB Ca²⁺/calmodulin sensing in P. falciparum not defined\",\n        \"CNB interactome beyond CnA and Hsp90-associated complex uncharacterized\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008599\",\n        \"supporting_discovery_ids\": [\n          0,\n          1,\n          2\n        ]\n      },\n      {\n        \"term_id\": \"GO:0005516\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0019855\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006816\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      },\n      {\n        \"term_id\": \"GO:0002080\",\n        \"supporting_discovery_ids\": [\n          2,\n          3\n        ]\n      },\n      {\n        \"term_id\": \"GO:0044409\",\n        \"supporting_discovery_ids\": [\n          3\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Calcineurin (PP2B) complex: CnA catalytic subunit + CNB regulatory subunit\",\n      \"Calcineurin–Hsp90 in vivo association\"\n    ],\n    \"partners\": [\n      \"CnA (calcineurin catalytic subunit)\",\n      \"Hsp90 (association with the calcineurin complex)\",\n      \"Calmodulin (binds via the CNB regulatory subunit for Ca²⁺ stimulation)\"\n    ],\n    \"other_free_text\": [\n      \"CNB mutations found in cyclosporin A-resistant P. falciparum clones and correlate with CsA-resistant phosphatase activity in vitro\",\n      \"Full-length calcineurin holoenzyme undergoes rapid in vivo proteolytic processing to a constitutively active, Ca²⁺-uncoupled catalytic core\",\n      \"Calcineurin activity required for Ca²⁺-dependent microneme exocytosis (PfAMA-1 secretion) via apical actin dephosphorylation/depolymerization\",\n      \"Calcineurin stabilizes receptor-dependent merozoite–erythrocyte attachment during invasion\",\n      \"In invasion studies CNB is implicated through complex membership rather than by individual genetic manipulation\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1451700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 4 cited papers name other catalogue genes (PF3D7_0322000, PF3D7_0708400, PF3D7_0804800). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1451700","name":null,"product":"calcineurin subunit B","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1315400","name":null,"product":"calcineurin subunit B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1230400","name":null,"product":"calcineurin subunit B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CNB","evaluation":null}