{"gene":"PF3D7_0802600","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2012,"finding":"ACbeta (PfACβ, PF3D7_0802600) was biochemically characterized as an adenylyl cyclase that synthesizes cAMP during the erythrocytic stage of P. falciparum; it displays marked pH dependence and sensitivity to small molecule inhibitors, one of which is selective for PfACβ relative to human soluble adenylyl cyclase (sAC), and these inhibitors kill intraerythrocytic parasites.","method":"Biochemical characterization of recombinant PfACβ (enzyme activity assays, pH-dependence, inhibitor profiling); parasite growth inhibition assays with selective small-molecule inhibitors","journal":"PLoS ONE","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro enzymatic characterization with inhibitor selectivity profiling, single lab, single study","pmids":["22761895"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Conditional disruption of ACbeta (ACβ, PF3D7_0802600) in P. falciparum asexual blood stages demonstrated that cAMP production by ACβ is critical for erythrocyte invasion, while key developmental steps preceding invasion still occur in its absence; downstream PKA activity (not ACβ itself) mediates cAMP-dependent phosphorylation of the cytoplasmic domain of AMA1 to regulate invasion.","method":"Conditional genetic disruption (DiCre-based conditional knockdown) of ACβ; phosphoproteomic quantification of cAMP-dependent phosphorylation sites; invasion assays; complementary PKA conditional disruption","journal":"PLoS Biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional loss-of-function with defined invasion phenotype, phosphoproteomic readout, and epistatic dissection of ACβ→PKA→AMA1 pathway in a single rigorous study","pmids":["31075098"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"A bicarbonate-sensitive cytoplasmic adenylyl cyclase in P. falciparum merozoites (consistent with ACbeta) is activated by low K+ environments (mimicking blood plasma), raising cytosolic cAMP levels that activate PKA and regulate microneme secretion during erythrocyte invasion; cAMP also regulates cytosolic Ca2+ via an Epac pathway.","method":"cAMP measurement assays; PKA activity assays; microneme secretion assays; pharmacological manipulation of cAMP and Ca2+ pathways in merozoites","journal":"PLoS Pathogens","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple pharmacological and biochemical readouts in a single lab; adenylyl cyclase identity inferred from context (bicarbonate-sensitive, cytoplasmic) but not genetically confirmed in this paper","pmids":["25522250"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"In Toxoplasma gondii, the ortholog of ACbeta (adenylate cyclase β, ACβ) localizes to a rhoptry subcompartment and its localization there depends on the ARO-interacting protein (AIP): in the absence of AIP, ACβ disappears from rhoptries. P. falciparum ARO was shown to interact with the same partners (including ACβ) as TgARO, indicating conservation of this rhoptry-localization mechanism in Apicomplexa.","method":"Fluorescence microscopy localization; genetic depletion of AIP in Toxoplasma; co-immunoprecipitation of ARO partners; functional complementation of TgARO depletion with PfARO","journal":"Journal of Cell Science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization and interaction data are from Toxoplasma gondii; P. falciparum ACβ involvement is inferred from PfARO complementation and partner conservation, not directly demonstrated in P. falciparum in this paper","pmids":["26769898"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ACbeta (PF3D7_0802600) is a bicarbonate-sensitive cytoplasmic adenylyl cyclase expressed in P. falciparum erythrocytic stages that is activated by low-K+ (blood-plasma-like) conditions to produce cAMP, which activates PKA and an Epac pathway to trigger microneme secretion and regulate erythrocyte invasion; conditional genetic disruption confirms ACbeta-derived cAMP and downstream PKA activity are essential for invasion, with PKA-mediated phosphorylation of AMA1's cytoplasmic domain as one defined effector mechanism, and its rhoptry subcompartment localization in related apicomplexan parasites depends on the ARO-interacting protein AIP."},"narrative":{"mechanistic_narrative":"ACbeta (PF3D7_0802600) is an adenylyl cyclase that synthesizes cAMP during the P. falciparum erythrocytic stage and is essential for erythrocyte invasion [PMID:22761895, PMID:31075098]. The recombinant enzyme is pH-dependent and can be blocked by small-molecule inhibitors, one of which is selective for ACbeta over human soluble adenylyl cyclase and kills intraerythrocytic parasites [PMID:22761895]. Conditional genetic disruption established that ACbeta-derived cAMP is specifically required at the invasion step, while earlier developmental stages proceed in its absence; the cAMP signal acts through PKA, which phosphorylates the cytoplasmic domain of AMA1 as one defined effector of invasion [PMID:31075098]. A bicarbonate-sensitive cytoplasmic adenylyl cyclase activity consistent with ACbeta is activated in merozoites by low-K+ (plasma-like) conditions, raising cytosolic cAMP to drive PKA activation and microneme secretion, with cAMP also feeding a Ca2+-regulating Epac pathway [PMID:25522250]. In the related apicomplexan Toxoplasma gondii, the ACbeta ortholog localizes to a rhoptry subcompartment in an AIP-dependent manner, and conservation of the ARO interaction network in P. falciparum implies a similar localization mechanism [PMID:26769898]. Beyond these findings, no further mechanistic detail for PF3D7_0802600 has been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing that PF3D7_0802600 is a genuine, druggable adenylyl cyclase active in blood-stage parasites answered whether this enzyme produces cAMP at all and whether it could be selectively targeted.","evidence":"Biochemical characterization of recombinant PfACbeta with pH-dependence and inhibitor profiling, plus parasite growth inhibition assays","pmids":["22761895"],"confidence":"Medium","gaps":["Physiological activator and cellular localization not defined in this study","Selectivity shown against human sAC but not against Plasmodium sibling cyclases","Enzymatic role not connected to a specific parasite phenotype genetically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Identifying that a bicarbonate-sensitive cytoplasmic cyclase activity is triggered by plasma-like low-K+ conditions and drives PKA-dependent microneme secretion connected cAMP production to the physiological signal a merozoite encounters at invasion.","evidence":"cAMP and PKA activity assays, microneme secretion assays, and pharmacological manipulation of cAMP/Ca2+ pathways in merozoites","pmids":["25522250"],"confidence":"Medium","gaps":["Cyclase identity inferred from bicarbonate-sensitivity/cytoplasmic context, not genetically confirmed as PF3D7_0802600 in this work","Molecular link between low-K+ sensing and enzyme activation unresolved","Epac effector and Ca2+-regulation mechanism not molecularly defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Defining where the enzyme resides — the ortholog localizing to a rhoptry subcompartment via the ARO/AIP interaction network — addressed how the cyclase is positioned relative to the invasion machinery.","evidence":"Fluorescence microscopy, AIP depletion, co-IP of ARO partners in Toxoplasma gondii, and PfARO complementation of TgARO depletion","pmids":["26769898"],"confidence":"Low","gaps":["Localization and AIP dependence demonstrated in Toxoplasma gondii, not directly in P. falciparum","P. falciparum ACbeta rhoptry localization inferred from partner conservation, not shown directly","Functional consequence of mislocalizing ACbeta not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Conditional genetic disruption settled whether ACbeta-derived cAMP is causally required for invasion and traced the downstream signaling arm, showing PKA acts on AMA1's cytoplasmic tail as an effector.","evidence":"DiCre conditional disruption of ACbeta, phosphoproteomics, invasion assays, and parallel PKA conditional disruption","pmids":["31075098"],"confidence":"High","gaps":["Full set of PKA/cAMP effectors beyond AMA1 not enumerated","Relationship between low-K+ activation and the essential invasion role not tested in the knockout","Contribution of the Epac/Ca2+ arm relative to PKA not dissected genetically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How ACbeta itself senses the invasion trigger (low-K+/bicarbonate), whether its rhoptry localization holds and is functionally required in P. falciparum, and the complete downstream effector set remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["Direct molecular mechanism of ACbeta activation by ionic environment unknown","P. falciparum ACbeta subcellular localization and AIP dependence not directly demonstrated","Structural model of the enzyme and full effector network undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PKA (DOWNSTREAM EFFECTOR ACTIVATED BY ACBETA-DERIVED CAMP) [#1, #2]","AMA1 (CYTOPLASMIC DOMAIN PHOSPHORYLATED BY PKA DOWNSTREAM OF ACBETA) [#1]","EPAC PATHWAY (CAMP-RESPONSIVE, REGULATES CYTOSOLIC CA2+) [#2]","ARO / AIP INTERACTION NETWORK (RHOPTRY LOCALIZATION, SHOWN FOR ORTHOLOG IN T. GONDII) [#3]"],"other_free_text":["Enzyme activity is bicarbonate-sensitive and pH-dependent, and is activated by low-K+ (plasma-like) conditions during erythrocyte invasion [#0, #2].","Selective small-molecule inhibitors of ACbeta (relative to human soluble adenylyl cyclase) kill intraerythrocytic parasites [#0].","Conditional disruption shows ACbeta-derived cAMP is essential specifically for erythrocyte invasion, not for preceding developmental steps [#1].","Rhoptry-subcompartment localization and AIP dependence were demonstrated for the Toxoplasma gondii ortholog and inferred for P. falciparum via ARO partner conservation, not directly shown in P. falciparum [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25522250","id":"PMC_25522250","title":"The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes.","date":"2014","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/25522250","citation_count":80,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31075098","id":"PMC_31075098","title":"Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.","date":"2019","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/31075098","citation_count":58,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACbeta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26769898","id":"PMC_26769898","title":"Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein.","date":"2016","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26769898","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACbeta"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"15590559","id":"PMC_15590559","title":"Adenylyl and guanylyl cyclases from the malaria parasite Plasmodium falciparum.","date":"2004","source":"IUBMB life","url":"https://pubmed.ncbi.nlm.nih.gov/15590559","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22761895","id":"PMC_22761895","title":"Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22761895","citation_count":21,"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":4679,"output_tokens":1453,"usd":0.017916,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6508,"output_tokens":2781,"usd":0.051033,"stage2_stop_reason":"end_turn"},"total_usd":0.068949,"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\": 2012,\n      \"finding\": \"ACbeta (PfACβ, PF3D7_0802600) was biochemically characterized as an adenylyl cyclase that synthesizes cAMP during the erythrocytic stage of P. falciparum; it displays marked pH dependence and sensitivity to small molecule inhibitors, one of which is selective for PfACβ relative to human soluble adenylyl cyclase (sAC), and these inhibitors kill intraerythrocytic parasites.\",\n      \"method\": \"Biochemical characterization of recombinant PfACβ (enzyme activity assays, pH-dependence, inhibitor profiling); parasite growth inhibition assays with selective small-molecule inhibitors\",\n      \"journal\": \"PLoS ONE\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro enzymatic characterization with inhibitor selectivity profiling, single lab, single study\",\n      \"pmids\": [\"22761895\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Conditional disruption of ACbeta (ACβ, PF3D7_0802600) in P. falciparum asexual blood stages demonstrated that cAMP production by ACβ is critical for erythrocyte invasion, while key developmental steps preceding invasion still occur in its absence; downstream PKA activity (not ACβ itself) mediates cAMP-dependent phosphorylation of the cytoplasmic domain of AMA1 to regulate invasion.\",\n      \"method\": \"Conditional genetic disruption (DiCre-based conditional knockdown) of ACβ; phosphoproteomic quantification of cAMP-dependent phosphorylation sites; invasion assays; complementary PKA conditional disruption\",\n      \"journal\": \"PLoS Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional loss-of-function with defined invasion phenotype, phosphoproteomic readout, and epistatic dissection of ACβ→PKA→AMA1 pathway in a single rigorous study\",\n      \"pmids\": [\"31075098\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"A bicarbonate-sensitive cytoplasmic adenylyl cyclase in P. falciparum merozoites (consistent with ACbeta) is activated by low K+ environments (mimicking blood plasma), raising cytosolic cAMP levels that activate PKA and regulate microneme secretion during erythrocyte invasion; cAMP also regulates cytosolic Ca2+ via an Epac pathway.\",\n      \"method\": \"cAMP measurement assays; PKA activity assays; microneme secretion assays; pharmacological manipulation of cAMP and Ca2+ pathways in merozoites\",\n      \"journal\": \"PLoS Pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple pharmacological and biochemical readouts in a single lab; adenylyl cyclase identity inferred from context (bicarbonate-sensitive, cytoplasmic) but not genetically confirmed in this paper\",\n      \"pmids\": [\"25522250\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In Toxoplasma gondii, the ortholog of ACbeta (adenylate cyclase β, ACβ) localizes to a rhoptry subcompartment and its localization there depends on the ARO-interacting protein (AIP): in the absence of AIP, ACβ disappears from rhoptries. P. falciparum ARO was shown to interact with the same partners (including ACβ) as TgARO, indicating conservation of this rhoptry-localization mechanism in Apicomplexa.\",\n      \"method\": \"Fluorescence microscopy localization; genetic depletion of AIP in Toxoplasma; co-immunoprecipitation of ARO partners; functional complementation of TgARO depletion with PfARO\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization and interaction data are from Toxoplasma gondii; P. falciparum ACβ involvement is inferred from PfARO complementation and partner conservation, not directly demonstrated in P. falciparum in this paper\",\n      \"pmids\": [\"26769898\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ACbeta (PF3D7_0802600) is a bicarbonate-sensitive cytoplasmic adenylyl cyclase expressed in P. falciparum erythrocytic stages that is activated by low-K+ (blood-plasma-like) conditions to produce cAMP, which activates PKA and an Epac pathway to trigger microneme secretion and regulate erythrocyte invasion; conditional genetic disruption confirms ACbeta-derived cAMP and downstream PKA activity are essential for invasion, with PKA-mediated phosphorylation of AMA1's cytoplasmic domain as one defined effector mechanism, and its rhoptry subcompartment localization in related apicomplexan parasites depends on the ARO-interacting protein AIP.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ACbeta (PF3D7_0802600) is an adenylyl cyclase that synthesizes cAMP during the P. falciparum erythrocytic stage and is essential for erythrocyte invasion [#0, #1]. The recombinant enzyme is pH-dependent and can be blocked by small-molecule inhibitors, one of which is selective for ACbeta over human soluble adenylyl cyclase and kills intraerythrocytic parasites [#0]. Conditional genetic disruption established that ACbeta-derived cAMP is specifically required at the invasion step, while earlier developmental stages proceed in its absence; the cAMP signal acts through PKA, which phosphorylates the cytoplasmic domain of AMA1 as one defined effector of invasion [#1]. A bicarbonate-sensitive cytoplasmic adenylyl cyclase activity consistent with ACbeta is activated in merozoites by low-K+ (plasma-like) conditions, raising cytosolic cAMP to drive PKA activation and microneme secretion, with cAMP also feeding a Ca2+-regulating Epac pathway [#2]. In the related apicomplexan Toxoplasma gondii, the ACbeta ortholog localizes to a rhoptry subcompartment in an AIP-dependent manner, and conservation of the ARO interaction network in P. falciparum implies a similar localization mechanism [#3]. Beyond these findings, no further mechanistic detail for PF3D7_0802600 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing that PF3D7_0802600 is a genuine, druggable adenylyl cyclase active in blood-stage parasites answered whether this enzyme produces cAMP at all and whether it could be selectively targeted.\",\n      \"evidence\": \"Biochemical characterization of recombinant PfACbeta with pH-dependence and inhibitor profiling, plus parasite growth inhibition assays\",\n      \"pmids\": [\"22761895\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological activator and cellular localization not defined in this study\", \"Selectivity shown against human sAC but not against Plasmodium sibling cyclases\", \"Enzymatic role not connected to a specific parasite phenotype genetically\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identifying that a bicarbonate-sensitive cytoplasmic cyclase activity is triggered by plasma-like low-K+ conditions and drives PKA-dependent microneme secretion connected cAMP production to the physiological signal a merozoite encounters at invasion.\",\n      \"evidence\": \"cAMP and PKA activity assays, microneme secretion assays, and pharmacological manipulation of cAMP/Ca2+ pathways in merozoites\",\n      \"pmids\": [\"25522250\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cyclase identity inferred from bicarbonate-sensitivity/cytoplasmic context, not genetically confirmed as PF3D7_0802600 in this work\", \"Molecular link between low-K+ sensing and enzyme activation unresolved\", \"Epac effector and Ca2+-regulation mechanism not molecularly defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defining where the enzyme resides — the ortholog localizing to a rhoptry subcompartment via the ARO/AIP interaction network — addressed how the cyclase is positioned relative to the invasion machinery.\",\n      \"evidence\": \"Fluorescence microscopy, AIP depletion, co-IP of ARO partners in Toxoplasma gondii, and PfARO complementation of TgARO depletion\",\n      \"pmids\": [\"26769898\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Localization and AIP dependence demonstrated in Toxoplasma gondii, not directly in P. falciparum\", \"P. falciparum ACbeta rhoptry localization inferred from partner conservation, not shown directly\", \"Functional consequence of mislocalizing ACbeta not tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Conditional genetic disruption settled whether ACbeta-derived cAMP is causally required for invasion and traced the downstream signaling arm, showing PKA acts on AMA1's cytoplasmic tail as an effector.\",\n      \"evidence\": \"DiCre conditional disruption of ACbeta, phosphoproteomics, invasion assays, and parallel PKA conditional disruption\",\n      \"pmids\": [\"31075098\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full set of PKA/cAMP effectors beyond AMA1 not enumerated\", \"Relationship between low-K+ activation and the essential invasion role not tested in the knockout\", \"Contribution of the Epac/Ca2+ arm relative to PKA not dissected genetically\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ACbeta itself senses the invasion trigger (low-K+/bicarbonate), whether its rhoptry localization holds and is functionally required in P. falciparum, and the complete downstream effector set remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Direct molecular mechanism of ACbeta activation by ionic environment unknown\", \"P. falciparum ACbeta subcellular localization and AIP dependence not directly demonstrated\", \"Structural model of the enzyme and full effector network undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004016\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006171\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0007155\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PKA (downstream effector activated by ACbeta-derived cAMP) [#1, #2]\",\n      \"AMA1 (cytoplasmic domain phosphorylated by PKA downstream of ACbeta) [#1]\",\n      \"Epac pathway (cAMP-responsive, regulates cytosolic Ca2+) [#2]\",\n      \"ARO / AIP interaction network (rhoptry localization, shown for ortholog in T. gondii) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Enzyme activity is bicarbonate-sensitive and pH-dependent, and is activated by low-K+ (plasma-like) conditions during erythrocyte invasion [#0, #2].\",\n      \"Selective small-molecule inhibitors of ACbeta (relative to human soluble adenylyl cyclase) kill intraerythrocytic parasites [#0].\",\n      \"Conditional disruption shows ACbeta-derived cAMP is essential specifically for erythrocyte invasion, not for preceding developmental steps [#1].\",\n      \"Rhoptry-subcompartment localization and AIP dependence were demonstrated for the Toxoplasma gondii ortholog and inferred for P. falciparum via ARO partner conservation, not directly shown in P. falciparum [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0802600","name":null,"product":"adenylyl cyclase beta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1227600","name":null,"product":"adenylyl cyclase beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0116300","name":null,"product":"adenylyl cyclase beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ACbeta","evaluation":null}