{"gene":"PF3D7_1418300","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":1991,"finding":"The P. falciparum calmodulin gene (PF3D7_1418300) exists as a single copy on chromosome 14, contains a single intron, and encodes a protein with 89% sequence identity to mammalian calmodulin. Primer extension studies identified a major transcription start site 62 bases upstream of the initial ATG.","method":"Southern blotting, DNA sequencing, primer extension","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct molecular characterization with multiple orthogonal methods (Southern blot, sequencing, primer extension) establishing gene structure","pmids":["1852174"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1991,"finding":"The calmodulin gene sequence and protein expression level are identical in chloroquine-resistant and chloroquine-sensitive P. falciparum isolates, indicating that alterations in calmodulin play no role in chloroquine resistance in the isolates tested.","method":"Southern blotting, Western blotting, DNA sequencing of cloned calmodulin gene","journal":"Experimental parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — negative mechanistic result established by multiple orthogonal methods (Southern blot, Western blot, sequencing), single lab","pmids":["1915742"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1987,"finding":"Calmodulin (PF3D7_1418300) was detected in P. falciparum by radioimmunoassay and immunoelectron microscopy localized it diffusely within the cytoplasm of mature parasites and concentrated at the apical end of merozoites within the ductule of rhoptries, suggesting a role in erythrocyte invasion.","method":"Radioimmunoassay, immunoelectron microscopy","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunoelectron microscopy replicated across two independent papers (PMID 3313391, 3127214) from the same era","pmids":["3313391"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1987,"finding":"Calmodulin antagonists (W7, trifluoperazine, R24571) inhibited erythrocyte invasion by P. falciparum merozoites and schizont maturation in a potency-correlated manner. Immunoelectron microscopy showed calmodulin concentrated at the apical end of free and intraerythrocytic merozoites, suggesting calmodulin accumulation at the apical pole is important for erythrocyte attachment and/or invasion.","method":"In vitro parasite growth assay, immunoelectron microscopy, calmodulin antagonist pharmacology","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunoelectron microscopy with functional pharmacological correlation, single lab but multiple orthogonal approaches","pmids":["3127214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1995,"finding":"Calmodulin mRNA and protein in P. falciparum are expressed in a stage-specific, cell cycle-linked manner: low in early ring stages, rising to peak at ~40 h (late trophozoite), with mRNA declining in final 8 h while protein continues to accumulate through schizonts. This pattern is regulated at the level of transcription and mRNA degradation, unlike classical constitutive housekeeping expression.","method":"Northern blotting, Western blotting, pulse-chase mRNA stability assays","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Northern blot, Western blot, pulse-chase), single lab","pmids":["8720124"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"Calmodulin (PF3D7_1418300) directly activates PfPKB (a protein kinase B-like enzyme) in a calcium-dependent manner. A calmodulin-binding domain was mapped to the N-terminal region of PfPKB; calmodulin interacts with this domain and activates PfPKB kinase activity. Calmodulin associates with PfPKB in parasite extracts, and phospholipase C acts upstream of this cascade by facilitating intracellular calcium release.","method":"Co-immunoprecipitation, calmodulin-binding domain mapping, in vitro kinase assay, calmodulin antagonist pharmacology","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and in vitro kinase assay with domain mapping, single lab, multiple orthogonal methods","pmids":["16809343"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Blocking calmodulin function (upstream of PfPKB) with calmodulin inhibitors impairs P. falciparum erythrocyte invasion. PfPKB, activated by calmodulin, associates with the actin-myosin motor and phosphorylates PfGAP45, a glideosome component, providing a mechanistic link between calmodulin/PfPKB signaling and invasion.","method":"Pharmacological inhibition of calmodulin and PfPKB, Co-immunoprecipitation, in vitro kinase assay with PfGAP45 as substrate, invasion assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, kinase assay, invasion assay), single lab","pmids":["18165240"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"finding":"P. falciparum calcineurin (PP2B-like phosphatase) is stimulated by calmodulin and Ca2+, establishing calmodulin as a direct activator of P. falciparum calcineurin activity.","method":"Purification of phosphatase from cytosolic extracts, biochemical activity assay with calmodulin and Ca2+ supplementation","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution with purified enzyme, single lab","pmids":["10340482"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"The P. falciparum calmodulin gene promoter (pfcam, PF3D7_1418300) drives transcription in P. falciparum and requires sequences between approximately -625 and -230 bp upstream of the ATG. Nuclear factors bind poly(dA)poly(dT) tracts in this region; binding correlated with poly(dA)poly(dT) density and the basal promoter activity diminished upon stepwise deletion. Multiple transcription-initiation sites were mapped, clustering into four ~30 bp regions within 180 bp upstream of the ORF.","method":"Oligo-capping/transcription start site mapping, electromobility shift assays (EMSA), CAT reporter deletion analysis","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (transcription start mapping, EMSA, reporter assays), single lab","pmids":["15850701"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Recombinantly expressed P. falciparum CaM (PF3D7_1418300) has higher conformational stability than human CaM, attributed to a more stable C-terminal domain in both Ca2+-free and Ca2+-saturated states. In vitro binding and functional assays showed Pf CaM and human CaM exhibit similar target enzyme activation and small-molecule inhibitor binding affinities (differing within a factor of three), and phenotypically active Malaria Box compounds could inhibit Pf CaM.","method":"Recombinant protein expression/purification, thermal stability assays, fluorescence-based binding assays, enzyme activation assays","journal":"FASEB bioAdvances","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution with recombinant protein, multiple orthogonal biophysical and functional assays, single lab","pmids":["32821880"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Crystal structures of Ca2+-saturated P. falciparum CaM (PF3D7_1418300) in complex with melittin reveal three distinct binding modes in which different residues anchor at the hydrophobic pockets, unlike the classical single-mode target recognition by CaM. Multiple co-existing conformers of similar stability achieve nanomolar binding affinity.","method":"X-ray crystallography, molecular dynamics simulations","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure of Pf CaM-melittin complex determined to high resolution, augmented by molecular dynamics simulations, rigorous structural characterization","pmids":["36906144"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Overexpression of P. falciparum calmodulin (PfCaM, PF3D7_1418300) in parasites results in a higher cytosolic Ca2+ rise after calmidazolium challenge and an increase in calcium-dependent proteolytic activity, indicating PfCaM participates in calcium homeostasis and modulation of intracellular proteolysis in P. falciparum erythrocytic stages.","method":"Transgenic overexpression (knockin with HA tag), live-cell calcium imaging (fluorescent Ca2+ indicator), fluorometric protease activity assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional overexpression with live calcium imaging and biochemical assay, single lab, multiple readouts","pmids":["29913151"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Using a knockin approach, CaM (PF3D7_1418300) was shown to be expressed and localized in all erythrocytic stages of P. falciparum. Calmidazolium (a CaM inhibitor) mobilized intracellular Ca2+ independent of the ER store, and the data implicate a CaM-related protein as a Ca2+ reservoir modulating calcium signaling and homeostasis during the intraerythrocytic cycle.","method":"Transgenic knockin, live-cell fluorescent Ca2+ imaging, pharmacological dissection with CaM inhibitors and organelle-targeted ionophores","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization via knockin with functional live-imaging readout, single lab, multiple orthogonal pharmacological approaches","pmids":["26689736"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"P. falciparum PP7 phosphatase physically interacts with calmodulin (PF3D7_1418300) and with CDPK1, consistent with a role in calcium signaling. This interaction was identified in the context of PP7 being a calcium-dependent phosphatase essential for early ring-stage development.","method":"Conditional gene disruption, phosphoproteomic analysis, co-immunoprecipitation/interaction assay (calmodulin interaction)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interaction with calmodulin identified biochemically in context of conditional KO with defined phenotype, single lab","pmids":["39387582"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"The calmodulin-like domain (CaM-LD) of MLC-B, the light chain of P. falciparum MyoB, binds to the MyoB IQ2 motif in vitro. Four additional putative regulatory light chains also bind the MyoB IQ2 motif in vitro, including calmodulin (PF3D7_1418300).","method":"Recombinant protein expression, in vitro binding assays, small-angle X-ray scattering","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — in vitro binding of Pf CaM to MyoB IQ2 motif reported as one of multiple light chains; single method, single lab, no functional follow-up for PF3D7_1418300 specifically","pmids":["36273584"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"P. falciparum MyoF has a long neck region with capacity to bind up to six copies of the calmodulin homologue PfCaM (PF3D7_1418300), as determined by structural prediction and biochemical pull-down assays.","method":"Structural prediction, pull-down/biochemical binding assays","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — structural prediction plus pull-down, single lab, binding of PfCaM to MyoF neck inferred but not rigorously validated by orthogonal methods","pmids":["42141018"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum calmodulin (PF3D7_1418300) is a single-copy, Ca2+-binding regulatory protein encoded on chromosome 14 whose expression is stage-specifically regulated (peaking in late trophozoites/schizonts) at both transcriptional and mRNA-stability levels; it localizes to the parasite cytoplasm and concentrates at the apical end of merozoites, where it activates downstream effectors including PfPKB (via a direct Ca2+-dependent interaction mapped to PfPKB's N-terminal domain), calcineurin/PP2B, and PP7, thereby linking intracellular Ca2+ signals to erythrocyte invasion (through PfPKB-mediated phosphorylation of the glideosome component PfGAP45), ring-stage development, and intracellular Ca2+ homeostasis and proteolysis; its crystal structure in complex with melittin reveals multiple non-classical binding modes at its hydrophobic pockets, and biophysical characterization shows it is more conformationally stable than human calmodulin while retaining similar target-activation and inhibitor-binding properties."},"narrative":{"mechanistic_narrative":"PF3D7_1418300 encodes Plasmodium falciparum calmodulin, a single-copy, single-intron Ca2+-binding regulatory protein on chromosome 14 that links intracellular Ca2+ signals to erythrocyte invasion and the intraerythrocytic cycle [PMID:1852174, PMID:18165240]. Its expression is cell cycle-linked, low in rings and peaking in late trophozoites/schizonts through combined control of transcription and mRNA stability [PMID:8720124, PMID:15850701], and the protein localizes diffusely in the cytoplasm of mature parasites while concentrating at the apical end of merozoites, consistent with a role in invasion [PMID:3313391, PMID:3127214]. Mechanistically, PfCaM acts as a Ca2+-dependent activator of downstream effectors: it directly binds and activates PfPKB via a calmodulin-binding domain in the kinase's N-terminus, and this activated PfPKB engages the actin-myosin motor and phosphorylates the glideosome component PfGAP45, coupling Ca2+ signaling to motility and invasion [PMID:16809343, PMID:18165240]; it also stimulates calcineurin/PP2B phosphatase activity [PMID:10340482] and physically interacts with the ring-stage phosphatase PP7 [PMID:39387582]. Beyond effector activation, PfCaM participates in intracellular Ca2+ homeostasis and calcium-dependent proteolysis, since its overexpression raises cytosolic Ca2+ responses and proteolytic activity [PMID:29913151, PMID:26689736]. Structurally, Ca2+-saturated PfCaM binds targets through multiple non-classical modes at its hydrophobic pockets and is more conformationally stable than human calmodulin owing to a more stable C-terminal domain, while retaining similar target activation and inhibitor binding [PMID:32821880, PMID:36906144].","teleology":[{"year":1987,"claim":"Establishing where calmodulin resides and whether it matters for the parasite life cycle was the first step; localization to the merozoite apical pole and pharmacological blockade of invasion tied it to erythrocyte entry.","evidence":"radioimmunoassay and immunoelectron microscopy plus calmodulin-antagonist growth/invasion assays in P. falciparum","pmids":["3313391","3127214"],"confidence":"Medium","gaps":["Antagonists are not calmodulin-specific, so invasion inhibition may reflect off-target effects","No molecular effector identified at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1991,"claim":"Defining the gene as a single-copy, single-intron locus 89% identical to mammalian calmodulin fixed its identity and ruled out a role in chloroquine resistance.","evidence":"Southern blotting, sequencing, and primer extension; comparison across chloroquine-resistant and -sensitive isolates in P. falciparum","pmids":["1852174","1915742"],"confidence":"High","gaps":["Sequence identity to mammalian CaM does not establish parasite-specific function","Resistance analysis limited to the isolates tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1995,"claim":"Whether calmodulin was a constitutive housekeeping product or a regulated one was resolved by showing cell cycle-linked expression controlled at transcription and mRNA-stability levels.","evidence":"Northern/Western blotting and pulse-chase mRNA stability assays in P. falciparum","pmids":["8720124"],"confidence":"Medium","gaps":["Regulatory factors driving the stage-specificity not identified","Link between expression timing and function not directly tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"claim":"The first defined downstream effector was established by reconstituting calmodulin/Ca2+ stimulation of parasite calcineurin, showing PfCaM functions as a canonical phosphatase activator.","evidence":"purification of the PP2B-like phosphatase from cytosolic extracts and activity assays with calmodulin and Ca2+ in P. falciparum","pmids":["10340482"],"confidence":"Medium","gaps":["In vivo relevance of calcineurin activation not demonstrated","Physiological substrates of the calcineurin cascade unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"The cis-elements driving stage-specific calmodulin transcription were mapped, defining a promoter dependent on poly(dA)poly(dT) tracts bound by nuclear factors.","evidence":"transcription start site mapping, EMSA, and CAT reporter deletion analysis of the pfcam promoter in P. falciparum","pmids":["15850701"],"confidence":"Medium","gaps":["Identity of the nuclear binding factors not determined","Mechanism connecting promoter elements to cell cycle timing unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"A direct signaling route to invasion was built by showing PfCaM activates PfPKB via an N-terminal calmodulin-binding domain and that activated PfPKB phosphorylates the glideosome component PfGAP45.","evidence":"Co-IP, calmodulin-binding domain mapping, in vitro kinase assays with PfGAP45 substrate, and invasion assays in P. falciparum","pmids":["16809343","18165240"],"confidence":"Medium","gaps":["Direct genetic ablation of the CaM-PfPKB interaction in vivo not performed","Contribution relative to other kinases in the motor complex unquantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Beyond effector activation, PfCaM was implicated in Ca2+ homeostasis and proteolysis by showing overexpression amplifies cytosolic Ca2+ responses and calcium-dependent protease activity.","evidence":"HA-knockin overexpression, live-cell Ca2+ imaging, and fluorometric protease assays in P. falciparum","pmids":["29913151","26689736"],"confidence":"Medium","gaps":["Overexpression phenotype may not reflect endogenous stoichiometry","The specific proteases affected are not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Comparing PfCaM biophysically to human CaM addressed its drug-target potential, revealing greater conformational stability from a more stable C-terminal domain despite similar target activation and inhibitor affinities.","evidence":"recombinant protein, thermal stability assays, fluorescence binding, and enzyme activation assays including Malaria Box compounds for P. falciparum CaM","pmids":["32821880"],"confidence":"Medium","gaps":["Selectivity window over human CaM is narrow (within threefold)","Cellular efficacy of inhibitors against endogenous PfCaM not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Structural analysis explained how PfCaM recognizes targets, showing multiple non-classical binding modes at its hydrophobic pockets that achieve nanomolar affinity via co-existing conformers.","evidence":"X-ray crystallography of Ca2+-saturated PfCaM-melittin complex with molecular dynamics simulations","pmids":["36906144"],"confidence":"High","gaps":["Non-classical modes shown with melittin, not with physiological parasite targets","Functional consequence of multi-mode binding not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Additional Ca2+-signaling connectivity was extended by demonstrating that PfCaM physically interacts with the essential ring-stage phosphatase PP7.","evidence":"conditional PP7 disruption with phosphoproteomics and co-immunoprecipitation identifying the calmodulin interaction in P. falciparum","pmids":["39387582"],"confidence":"Medium","gaps":["Functional significance of the CaM-PP7 interaction for PfCaM not established","Interaction interface not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"In vitro binding surveys placed PfCaM as a candidate light chain for parasite myosins, binding the MyoB IQ2 motif and up to six sites in the MyoF neck.","evidence":"recombinant binding assays, small-angle X-ray scattering, structural prediction and pull-downs for MyoB and MyoF in P. falciparum","pmids":["36273584","42141018"],"confidence":"Low","gaps":["Binding shown in vitro without functional validation for PfCaM specifically","PfCaM is one of several candidate light chains, so physiological role at these myosins is uncertain"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PfCaM selects among its many effectors (PfPKB, calcineurin, PP7, candidate myosins) in space and time during the intraerythrocytic cycle, and whether it is genetically essential, remains unresolved.","evidence":"no direct evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No conditional knockout of PF3D7_1418300 itself reported","Effector selection and stage-specific partitioning of Ca2+ signals unmapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPKB","CALCINEURIN/PP2B","PP7","PFGAP45 (SUBSTRATE OF CAM-ACTIVATED PFPKB)","MYOB (IQ2 MOTIF)","MYOF (NECK REGION)"],"other_free_text":["Single-copy, single-intron gene on chromosome 14; 89% identical to mammalian calmodulin [#0]","No role in chloroquine resistance in isolates tested [#1]","Stage-specific expression peaking in late trophozoites/schizonts, regulated by transcription and mRNA stability [#4, #8]","More conformationally stable than human CaM due to a more stable C-terminal domain [#9]","Binds targets via multiple non-classical modes at hydrophobic pockets (crystallography with melittin) [#10]","Candidate drug target sensitive to Malaria Box compounds in vitro [#9]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16072038","id":"PMC_16072038","title":"Plants, symbiosis and parasites: a calcium signalling connection.","date":"2005","source":"Nature reviews. 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Primer extension studies identified a major transcription start site 62 bases upstream of the initial ATG.\",\n      \"method\": \"Southern blotting, DNA sequencing, primer extension\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct molecular characterization with multiple orthogonal methods (Southern blot, sequencing, primer extension) establishing gene structure\",\n      \"pmids\": [\"1852174\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1991,\n      \"finding\": \"The calmodulin gene sequence and protein expression level are identical in chloroquine-resistant and chloroquine-sensitive P. falciparum isolates, indicating that alterations in calmodulin play no role in chloroquine resistance in the isolates tested.\",\n      \"method\": \"Southern blotting, Western blotting, DNA sequencing of cloned calmodulin gene\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — negative mechanistic result established by multiple orthogonal methods (Southern blot, Western blot, sequencing), single lab\",\n      \"pmids\": [\"1915742\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1987,\n      \"finding\": \"Calmodulin (PF3D7_1418300) was detected in P. falciparum by radioimmunoassay and immunoelectron microscopy localized it diffusely within the cytoplasm of mature parasites and concentrated at the apical end of merozoites within the ductule of rhoptries, suggesting a role in erythrocyte invasion.\",\n      \"method\": \"Radioimmunoassay, immunoelectron microscopy\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunoelectron microscopy replicated across two independent papers (PMID 3313391, 3127214) from the same era\",\n      \"pmids\": [\"3313391\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1987,\n      \"finding\": \"Calmodulin antagonists (W7, trifluoperazine, R24571) inhibited erythrocyte invasion by P. falciparum merozoites and schizont maturation in a potency-correlated manner. Immunoelectron microscopy showed calmodulin concentrated at the apical end of free and intraerythrocytic merozoites, suggesting calmodulin accumulation at the apical pole is important for erythrocyte attachment and/or invasion.\",\n      \"method\": \"In vitro parasite growth assay, immunoelectron microscopy, calmodulin antagonist pharmacology\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunoelectron microscopy with functional pharmacological correlation, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"3127214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Calmodulin mRNA and protein in P. falciparum are expressed in a stage-specific, cell cycle-linked manner: low in early ring stages, rising to peak at ~40 h (late trophozoite), with mRNA declining in final 8 h while protein continues to accumulate through schizonts. This pattern is regulated at the level of transcription and mRNA degradation, unlike classical constitutive housekeeping expression.\",\n      \"method\": \"Northern blotting, Western blotting, pulse-chase mRNA stability assays\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Northern blot, Western blot, pulse-chase), single lab\",\n      \"pmids\": [\"8720124\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Calmodulin (PF3D7_1418300) directly activates PfPKB (a protein kinase B-like enzyme) in a calcium-dependent manner. A calmodulin-binding domain was mapped to the N-terminal region of PfPKB; calmodulin interacts with this domain and activates PfPKB kinase activity. Calmodulin associates with PfPKB in parasite extracts, and phospholipase C acts upstream of this cascade by facilitating intracellular calcium release.\",\n      \"method\": \"Co-immunoprecipitation, calmodulin-binding domain mapping, in vitro kinase assay, calmodulin antagonist pharmacology\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and in vitro kinase assay with domain mapping, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"16809343\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Blocking calmodulin function (upstream of PfPKB) with calmodulin inhibitors impairs P. falciparum erythrocyte invasion. PfPKB, activated by calmodulin, associates with the actin-myosin motor and phosphorylates PfGAP45, a glideosome component, providing a mechanistic link between calmodulin/PfPKB signaling and invasion.\",\n      \"method\": \"Pharmacological inhibition of calmodulin and PfPKB, Co-immunoprecipitation, in vitro kinase assay with PfGAP45 as substrate, invasion assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, kinase assay, invasion assay), single lab\",\n      \"pmids\": [\"18165240\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"P. falciparum calcineurin (PP2B-like phosphatase) is stimulated by calmodulin and Ca2+, establishing calmodulin as a direct activator of P. falciparum calcineurin activity.\",\n      \"method\": \"Purification of phosphatase from cytosolic extracts, biochemical activity assay with calmodulin and Ca2+ supplementation\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution with purified enzyme, single lab\",\n      \"pmids\": [\"10340482\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The P. falciparum calmodulin gene promoter (pfcam, PF3D7_1418300) drives transcription in P. falciparum and requires sequences between approximately -625 and -230 bp upstream of the ATG. Nuclear factors bind poly(dA)poly(dT) tracts in this region; binding correlated with poly(dA)poly(dT) density and the basal promoter activity diminished upon stepwise deletion. Multiple transcription-initiation sites were mapped, clustering into four ~30 bp regions within 180 bp upstream of the ORF.\",\n      \"method\": \"Oligo-capping/transcription start site mapping, electromobility shift assays (EMSA), CAT reporter deletion analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (transcription start mapping, EMSA, reporter assays), single lab\",\n      \"pmids\": [\"15850701\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Recombinantly expressed P. falciparum CaM (PF3D7_1418300) has higher conformational stability than human CaM, attributed to a more stable C-terminal domain in both Ca2+-free and Ca2+-saturated states. In vitro binding and functional assays showed Pf CaM and human CaM exhibit similar target enzyme activation and small-molecule inhibitor binding affinities (differing within a factor of three), and phenotypically active Malaria Box compounds could inhibit Pf CaM.\",\n      \"method\": \"Recombinant protein expression/purification, thermal stability assays, fluorescence-based binding assays, enzyme activation assays\",\n      \"journal\": \"FASEB bioAdvances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution with recombinant protein, multiple orthogonal biophysical and functional assays, single lab\",\n      \"pmids\": [\"32821880\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Crystal structures of Ca2+-saturated P. falciparum CaM (PF3D7_1418300) in complex with melittin reveal three distinct binding modes in which different residues anchor at the hydrophobic pockets, unlike the classical single-mode target recognition by CaM. Multiple co-existing conformers of similar stability achieve nanomolar binding affinity.\",\n      \"method\": \"X-ray crystallography, molecular dynamics simulations\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure of Pf CaM-melittin complex determined to high resolution, augmented by molecular dynamics simulations, rigorous structural characterization\",\n      \"pmids\": [\"36906144\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Overexpression of P. falciparum calmodulin (PfCaM, PF3D7_1418300) in parasites results in a higher cytosolic Ca2+ rise after calmidazolium challenge and an increase in calcium-dependent proteolytic activity, indicating PfCaM participates in calcium homeostasis and modulation of intracellular proteolysis in P. falciparum erythrocytic stages.\",\n      \"method\": \"Transgenic overexpression (knockin with HA tag), live-cell calcium imaging (fluorescent Ca2+ indicator), fluorometric protease activity assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional overexpression with live calcium imaging and biochemical assay, single lab, multiple readouts\",\n      \"pmids\": [\"29913151\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Using a knockin approach, CaM (PF3D7_1418300) was shown to be expressed and localized in all erythrocytic stages of P. falciparum. Calmidazolium (a CaM inhibitor) mobilized intracellular Ca2+ independent of the ER store, and the data implicate a CaM-related protein as a Ca2+ reservoir modulating calcium signaling and homeostasis during the intraerythrocytic cycle.\",\n      \"method\": \"Transgenic knockin, live-cell fluorescent Ca2+ imaging, pharmacological dissection with CaM inhibitors and organelle-targeted ionophores\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization via knockin with functional live-imaging readout, single lab, multiple orthogonal pharmacological approaches\",\n      \"pmids\": [\"26689736\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"P. falciparum PP7 phosphatase physically interacts with calmodulin (PF3D7_1418300) and with CDPK1, consistent with a role in calcium signaling. This interaction was identified in the context of PP7 being a calcium-dependent phosphatase essential for early ring-stage development.\",\n      \"method\": \"Conditional gene disruption, phosphoproteomic analysis, co-immunoprecipitation/interaction assay (calmodulin interaction)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interaction with calmodulin identified biochemically in context of conditional KO with defined phenotype, single lab\",\n      \"pmids\": [\"39387582\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The calmodulin-like domain (CaM-LD) of MLC-B, the light chain of P. falciparum MyoB, binds to the MyoB IQ2 motif in vitro. Four additional putative regulatory light chains also bind the MyoB IQ2 motif in vitro, including calmodulin (PF3D7_1418300).\",\n      \"method\": \"Recombinant protein expression, in vitro binding assays, small-angle X-ray scattering\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — in vitro binding of Pf CaM to MyoB IQ2 motif reported as one of multiple light chains; single method, single lab, no functional follow-up for PF3D7_1418300 specifically\",\n      \"pmids\": [\"36273584\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"P. falciparum MyoF has a long neck region with capacity to bind up to six copies of the calmodulin homologue PfCaM (PF3D7_1418300), as determined by structural prediction and biochemical pull-down assays.\",\n      \"method\": \"Structural prediction, pull-down/biochemical binding assays\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — structural prediction plus pull-down, single lab, binding of PfCaM to MyoF neck inferred but not rigorously validated by orthogonal methods\",\n      \"pmids\": [\"42141018\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum calmodulin (PF3D7_1418300) is a single-copy, Ca2+-binding regulatory protein encoded on chromosome 14 whose expression is stage-specifically regulated (peaking in late trophozoites/schizonts) at both transcriptional and mRNA-stability levels; it localizes to the parasite cytoplasm and concentrates at the apical end of merozoites, where it activates downstream effectors including PfPKB (via a direct Ca2+-dependent interaction mapped to PfPKB's N-terminal domain), calcineurin/PP2B, and PP7, thereby linking intracellular Ca2+ signals to erythrocyte invasion (through PfPKB-mediated phosphorylation of the glideosome component PfGAP45), ring-stage development, and intracellular Ca2+ homeostasis and proteolysis; its crystal structure in complex with melittin reveals multiple non-classical binding modes at its hydrophobic pockets, and biophysical characterization shows it is more conformationally stable than human calmodulin while retaining similar target-activation and inhibitor-binding properties.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1418300 encodes Plasmodium falciparum calmodulin, a single-copy, single-intron Ca2+-binding regulatory protein on chromosome 14 that links intracellular Ca2+ signals to erythrocyte invasion and the intraerythrocytic cycle [#0, #6]. Its expression is cell cycle-linked, low in rings and peaking in late trophozoites/schizonts through combined control of transcription and mRNA stability [#4, #8], and the protein localizes diffusely in the cytoplasm of mature parasites while concentrating at the apical end of merozoites, consistent with a role in invasion [#2, #3]. Mechanistically, PfCaM acts as a Ca2+-dependent activator of downstream effectors: it directly binds and activates PfPKB via a calmodulin-binding domain in the kinase's N-terminus, and this activated PfPKB engages the actin-myosin motor and phosphorylates the glideosome component PfGAP45, coupling Ca2+ signaling to motility and invasion [#5, #6]; it also stimulates calcineurin/PP2B phosphatase activity [#7] and physically interacts with the ring-stage phosphatase PP7 [#13]. Beyond effector activation, PfCaM participates in intracellular Ca2+ homeostasis and calcium-dependent proteolysis, since its overexpression raises cytosolic Ca2+ responses and proteolytic activity [#11, #12]. Structurally, Ca2+-saturated PfCaM binds targets through multiple non-classical modes at its hydrophobic pockets and is more conformationally stable than human calmodulin owing to a more stable C-terminal domain, while retaining similar target activation and inhibitor binding [#9, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 1987,\n      \"claim\": \"Establishing where calmodulin resides and whether it matters for the parasite life cycle was the first step; localization to the merozoite apical pole and pharmacological blockade of invasion tied it to erythrocyte entry.\",\n      \"evidence\": \"radioimmunoassay and immunoelectron microscopy plus calmodulin-antagonist growth/invasion assays in P. falciparum\",\n      \"pmids\": [\"3313391\", \"3127214\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Antagonists are not calmodulin-specific, so invasion inhibition may reflect off-target effects\", \"No molecular effector identified at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1991,\n      \"claim\": \"Defining the gene as a single-copy, single-intron locus 89% identical to mammalian calmodulin fixed its identity and ruled out a role in chloroquine resistance.\",\n      \"evidence\": \"Southern blotting, sequencing, and primer extension; comparison across chloroquine-resistant and -sensitive isolates in P. falciparum\",\n      \"pmids\": [\"1852174\", \"1915742\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Sequence identity to mammalian CaM does not establish parasite-specific function\", \"Resistance analysis limited to the isolates tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Whether calmodulin was a constitutive housekeeping product or a regulated one was resolved by showing cell cycle-linked expression controlled at transcription and mRNA-stability levels.\",\n      \"evidence\": \"Northern/Western blotting and pulse-chase mRNA stability assays in P. falciparum\",\n      \"pmids\": [\"8720124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulatory factors driving the stage-specificity not identified\", \"Link between expression timing and function not directly tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"The first defined downstream effector was established by reconstituting calmodulin/Ca2+ stimulation of parasite calcineurin, showing PfCaM functions as a canonical phosphatase activator.\",\n      \"evidence\": \"purification of the PP2B-like phosphatase from cytosolic extracts and activity assays with calmodulin and Ca2+ in P. falciparum\",\n      \"pmids\": [\"10340482\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo relevance of calcineurin activation not demonstrated\", \"Physiological substrates of the calcineurin cascade unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"The cis-elements driving stage-specific calmodulin transcription were mapped, defining a promoter dependent on poly(dA)poly(dT) tracts bound by nuclear factors.\",\n      \"evidence\": \"transcription start site mapping, EMSA, and CAT reporter deletion analysis of the pfcam promoter in P. falciparum\",\n      \"pmids\": [\"15850701\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the nuclear binding factors not determined\", \"Mechanism connecting promoter elements to cell cycle timing unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"A direct signaling route to invasion was built by showing PfCaM activates PfPKB via an N-terminal calmodulin-binding domain and that activated PfPKB phosphorylates the glideosome component PfGAP45.\",\n      \"evidence\": \"Co-IP, calmodulin-binding domain mapping, in vitro kinase assays with PfGAP45 substrate, and invasion assays in P. falciparum\",\n      \"pmids\": [\"16809343\", \"18165240\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct genetic ablation of the CaM-PfPKB interaction in vivo not performed\", \"Contribution relative to other kinases in the motor complex unquantified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Beyond effector activation, PfCaM was implicated in Ca2+ homeostasis and proteolysis by showing overexpression amplifies cytosolic Ca2+ responses and calcium-dependent protease activity.\",\n      \"evidence\": \"HA-knockin overexpression, live-cell Ca2+ imaging, and fluorometric protease assays in P. falciparum\",\n      \"pmids\": [\"29913151\", \"26689736\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression phenotype may not reflect endogenous stoichiometry\", \"The specific proteases affected are not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Comparing PfCaM biophysically to human CaM addressed its drug-target potential, revealing greater conformational stability from a more stable C-terminal domain despite similar target activation and inhibitor affinities.\",\n      \"evidence\": \"recombinant protein, thermal stability assays, fluorescence binding, and enzyme activation assays including Malaria Box compounds for P. falciparum CaM\",\n      \"pmids\": [\"32821880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Selectivity window over human CaM is narrow (within threefold)\", \"Cellular efficacy of inhibitors against endogenous PfCaM not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Structural analysis explained how PfCaM recognizes targets, showing multiple non-classical binding modes at its hydrophobic pockets that achieve nanomolar affinity via co-existing conformers.\",\n      \"evidence\": \"X-ray crystallography of Ca2+-saturated PfCaM-melittin complex with molecular dynamics simulations\",\n      \"pmids\": [\"36906144\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Non-classical modes shown with melittin, not with physiological parasite targets\", \"Functional consequence of multi-mode binding not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Additional Ca2+-signaling connectivity was extended by demonstrating that PfCaM physically interacts with the essential ring-stage phosphatase PP7.\",\n      \"evidence\": \"conditional PP7 disruption with phosphoproteomics and co-immunoprecipitation identifying the calmodulin interaction in P. falciparum\",\n      \"pmids\": [\"39387582\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional significance of the CaM-PP7 interaction for PfCaM not established\", \"Interaction interface not mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"In vitro binding surveys placed PfCaM as a candidate light chain for parasite myosins, binding the MyoB IQ2 motif and up to six sites in the MyoF neck.\",\n      \"evidence\": \"recombinant binding assays, small-angle X-ray scattering, structural prediction and pull-downs for MyoB and MyoF in P. falciparum\",\n      \"pmids\": [\"36273584\", \"42141018\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Binding shown in vitro without functional validation for PfCaM specifically\", \"PfCaM is one of several candidate light chains, so physiological role at these myosins is uncertain\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfCaM selects among its many effectors (PfPKB, calcineurin, PP7, candidate myosins) in space and time during the intraerythrocytic cycle, and whether it is genetically essential, remains unresolved.\",\n      \"evidence\": \"no direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No conditional knockout of PF3D7_1418300 itself reported\", \"Effector selection and stage-specific partitioning of Ca2+ signals unmapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [9, 10, 11]},\n      {\"term_id\": \"GO:0004683\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"GO:0008427\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [5, 13, 14, 15]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [2, 12]},\n      {\"term_id\": \"GO:0020007\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019722\", \"supporting_discovery_ids\": [5, 11, 12, 13]},\n      {\"term_id\": \"GO:0006812\", \"supporting_discovery_ids\": [11, 12]},\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [3, 6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfPKB\",\n      \"calcineurin/PP2B\",\n      \"PP7\",\n      \"PfGAP45 (substrate of CaM-activated PfPKB)\",\n      \"MyoB (IQ2 motif)\",\n      \"MyoF (neck region)\"\n    ],\n    \"other_free_text\": [\n      \"Single-copy, single-intron gene on chromosome 14; 89% identical to mammalian calmodulin [#0]\",\n      \"No role in chloroquine resistance in isolates tested [#1]\",\n      \"Stage-specific expression peaking in late trophozoites/schizonts, regulated by transcription and mRNA stability [#4, #8]\",\n      \"More conformationally stable than human CaM due to a more stable C-terminal domain [#9]\",\n      \"Binds targets via multiple non-classical modes at hydrophobic pockets (crystallography with melittin) [#10]\",\n      \"Candidate drug target sensitive to Malaria Box compounds in vitro [#9]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1418300","name":null,"product":"calmodulin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1024400","name":null,"product":"calmodulin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1339700","name":null,"product":"calmodulin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}