{"gene":"PF3D7_1313300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":1994,"finding":"Peptidyl-prolyl cis-trans isomerase (PPIase) activity was detected in P. falciparum extracts; this activity was completely inhibited by cyclosporin A at concentrations above 0.1 µM but not by FK506 or rapamycin, indicating it is attributable to cyclophilin(s), not FKBPs. Additionally, the P. falciparum cyclophilin-containing extract, in combination with cyclosporin A, inhibited the protein phosphatase activity of bovine calcineurin in vitro.","method":"In vitro PPIase activity assay on P. falciparum cell-free extracts; in vitro calcineurin phosphatase inhibition assay with parasite extract plus cyclosporin A","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro enzymatic assay with inhibitor panel, single lab, but activity attributed to unresolved cyclophilin mixture in crude extract, not specifically to PF3D7_1313300","pmids":["7520696"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Among 8 recombinantly expressed P. falciparum cyclophilin family members, only two displayed PPIase (isomerase) activity, while all eight displayed molecular chaperone activity as measured by prevention of thermal aggregation of model substrates. PF3D7_1313300 is one member of this family assessed in this study; the specific activity profile attributed to each individual member is not distinguished in the abstract beyond this family-level summary.","method":"Recombinant protein expression in E. coli; in vitro PPIase activity assay; thermal aggregation prevention chaperone assay","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 2 / Weak — two orthogonal enzymatic assays used, but abstract does not specify which individual cyclophilin family members had PPIase activity versus chaperone-only activity, so specific assignment to PF3D7_1313300 cannot be made","pmids":["22546550"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"All 11 P. falciparum cyclophilin or cyclophilin-like proteins (including PF3D7_1313300) were produced recombinantly with a C-terminal His6 tag in E. coli using an identical expression system; recombinant proteins were assessed by thermal melt assay for correct folding and cyclosporin A binding, enabling family-wide functional comparisons.","method":"Recombinant expression and purification in E. coli; thermal melt assay for folding and cyclosporin A binding","journal":"Protein expression and purification","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single set of assays (thermal melt), abstract does not report specific binding or folding results for PF3D7_1313300 individually","pmids":["21549842"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Mass spectrometry-based interactome mapping of PP1c (protein phosphatase 1 catalytic subunit) and its inhibitor I2 in P. berghei identified a peptidyl-prolyl cis-trans isomerase (ortholog of PF3D7_1313300) as a candidate interactor of the PP1c/I2 complex in both asexual (schizont) and sexual (gametocyte) stages, suggesting it may be a target of this phosphatase regulatory complex.","method":"mCherry-tagged PP1c and I2 affinity pulldown from P. berghei transgenic parasites followed by mass spectrometry","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown-MS method, interaction inferred from co-purification without direct validation of physical interaction with PF3D7_1313300 specifically","pmids":["35162991"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1313300 is a member of the P. falciparum cyclophilin family with putative peptidyl-prolyl cis-trans isomerase and/or molecular chaperone activities (as established for the family by recombinant biochemical assays), cyclosporin A sensitivity has been demonstrated at the family level in parasite extracts, and interactome data from P. berghei suggest it may associate with the PP1c/inhibitor-2 phosphatase regulatory complex; however, no experiment has directly and specifically characterized the enzymatic activity, binding partners, structure, or in-parasite function of PF3D7_1313300 itself."},"narrative":{"mechanistic_narrative":"PF3D7_1313300 is annotated as a member of the Plasmodium falciparum cyclophilin family, a group of putative peptidyl-prolyl cis-trans isomerases and/or molecular chaperones assessed collectively by recombinant biochemistry [PMID:22546550, PMID:21549842]. In P. falciparum extracts, cyclophilin-attributable PPIase activity is inhibited by cyclosporin A but not FK506 or rapamycin, and the cyclosporin A-bound cyclophilin fraction inhibits calcineurin phosphatase activity in vitro; however, this activity derives from an unresolved cyclophilin mixture and is not specifically assigned to PF3D7_1313300 [PMID:7520696]. Across the recombinantly expressed family, only two of eight members showed PPIase activity while all eight showed chaperone activity, but the abstracts do not resolve which activity profile belongs to PF3D7_1313300 individually [PMID:22546550, PMID:21549842]. In P. berghei, the ortholog of PF3D7_1313300 was recovered as a candidate interactor of the PP1c/inhibitor-2 phosphatase regulatory complex in both asexual and sexual stages by affinity pulldown-mass spectrometry [PMID:35162991]. Beyond family-level membership and this single co-purification, no experiment has directly characterized the enzymatic activity, binding partners, structure, or in-parasite function of PF3D7_1313300 itself in the available corpus.","teleology":[{"year":1994,"claim":"Establishing whether P. falciparum harbors cyclosporin A-sensitive PPIase activity distinguished cyclophilins from FKBPs as the drug-relevant isomerases and linked this activity to calcineurin regulation, but did not resolve which of many cyclophilins was responsible.","evidence":"In vitro PPIase assay with an inhibitor panel and a calcineurin phosphatase inhibition assay on P. falciparum cell-free extracts","pmids":["7520696"],"confidence":"Medium","gaps":["Activity attributed to an unresolved cyclophilin mixture, not to PF3D7_1313300 specifically","No demonstration that PF3D7_1313300 contributes to the calcineurin-inhibitory activity","No in-parasite functional assignment"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Recombinant production of all 11 P. falciparum cyclophilin/cyclophilin-like proteins, including PF3D7_1313300, under a uniform system enabled family-wide folding and cyclosporin A binding comparison, but did not report PF3D7_1313300-specific results.","evidence":"Recombinant expression and purification in E. coli with thermal melt assays for folding and cyclosporin A binding","pmids":["21549842"],"confidence":"Low","gaps":["Abstract does not report specific folding or cyclosporin A binding data for PF3D7_1313300","No enzymatic characterization","No structural model"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Orthogonal PPIase and chaperone assays across eight recombinant family members showed the family is functionally split (isomerase-active minority, chaperone-active majority), but the specific activity of PF3D7_1313300 was not distinguished.","evidence":"In vitro PPIase activity assay and thermal aggregation prevention chaperone assay on recombinant proteins","pmids":["22546550"],"confidence":"Low","gaps":["Whether PF3D7_1313300 is one of the two PPIase-active members is unstated","No substrate identity","No in-parasite validation of chaperone or isomerase role"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Interactome mapping of the PP1c/inhibitor-2 phosphatase complex provided the first candidate physiological context for the PF3D7_1313300 ortholog, placing it near a phosphatase regulatory hub across asexual and sexual stages.","evidence":"mCherry-tagged PP1c and I2 affinity pulldown from P. berghei transgenic parasites followed by mass spectrometry","pmids":["35162991"],"confidence":"Low","gaps":["Co-purification not validated as a direct physical interaction","Shown for the P. berghei ortholog, not P. falciparum PF3D7_1313300 directly","Functional consequence of the association is unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct enzymatic activity, substrates, binding partners, structure, and in-parasite function of PF3D7_1313300 itself remain uncharacterized, as all current evidence is either family-level or from an ortholog co-purification.","evidence":"","pmids":[],"confidence":"Low","gaps":["No member-specific PPIase or chaperone activity established for PF3D7_1313300","No genetic knockout/knockdown phenotype in either species","No validated direct binding partner for PF3D7_1313300"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PP1c/inhibitor-2 phosphatase regulatory complex (candidate interactor, P. berghei ortholog) [#3]"],"partners":["PP1C (CANDIDATE, VIA ORTHOLOG CO-PURIFICATION) [#3]","INHIBITOR-2 / I2 (CANDIDATE, VIA ORTHOLOG CO-PURIFICATION) [#3]"],"other_free_text":["PF3D7_1313300 is a member of the P. falciparum cyclophilin family; no experiment in the corpus assigns member-specific enzymatic, chaperone, structural, or in-parasite functional properties to PF3D7_1313300 itself [#1, #2].","Cyclosporin A-sensitive, FK506/rapamycin-insensitive PPIase activity was demonstrated at the level of P. falciparum extracts (unresolved cyclophilin mixture), not specifically for PF3D7_1313300 [#0].","The PP1c/I2 association is reported for the P. berghei ortholog, not P. falciparum PF3D7_1313300 directly [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"7520696","id":"PMC_7520696","title":"Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of antimalarial action of cyclosporin A, FK506, and rapamycin.","date":"1994","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/7520696","citation_count":108,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15664653","id":"PMC_15664653","title":"A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15664653","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25986569","id":"PMC_25986569","title":"Immunophilins: Structures, Mechanisms and Ligands.","date":"2015","source":"Current molecular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25986569","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8577319","id":"PMC_8577319","title":"Cloning and characterization of a Plasmodium falciparum cyclophilin gene that is stage-specifically expressed.","date":"1995","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8577319","citation_count":37,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12906882","id":"PMC_12906882","title":"Cyclosporin-binding proteins of Plasmodium falciparum.","date":"2003","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/12906882","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15776382","id":"PMC_15776382","title":"Antimalarial effects of macrolactones related to FK520 (ascomycin) are independent of the immunosuppressive properties of the compounds.","date":"2005","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/15776382","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22546550","id":"PMC_22546550","title":"A family of cyclophilin-like molecular chaperones in Plasmodium falciparum.","date":"2012","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/22546550","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21549842","id":"PMC_21549842","title":"Overexpression, purification and assessment of cyclosporin binding of a family of cyclophilins and cyclophilin-like proteins of the human malarial parasite Plasmodium falciparum.","date":"2011","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/21549842","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26869851","id":"PMC_26869851","title":"Protein profiling of mefloquine resistant Plasmodium falciparum using mass spectrometry-based proteomics.","date":"2015","source":"International journal of mass spectrometry","url":"https://pubmed.ncbi.nlm.nih.gov/26869851","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33202000","id":"PMC_33202000","title":"A proteomic glimpse into the effect of antimalarial drugs on Plasmodium falciparum proteome towards highlighting possible therapeutic targets.","date":"2021","source":"Pathogens and disease","url":"https://pubmed.ncbi.nlm.nih.gov/33202000","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26091727","id":"PMC_26091727","title":"Computational insights into the suicide inhibition of Plasmodium falciparum Fk506-binding protein 35.","date":"2015","source":"Bioorganic & medicinal chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/26091727","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25978804","id":"PMC_25978804","title":"Molecular docking study of macrocycles as Fk506-binding protein inhibitors.","date":"2015","source":"Journal of molecular graphics & modelling","url":"https://pubmed.ncbi.nlm.nih.gov/25978804","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35162991","id":"PMC_35162991","title":"Mapping PP1c and Its Inhibitor 2 Interactomes Reveals Conserved and Specific Networks in Asexual and Sexual Stages of Plasmodium.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35162991","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31120120","id":"PMC_31120120","title":"Expression and characterization of functional domains of FK506-binding protein 35 from Plasmodium knowlesi.","date":"2018","source":"Protein engineering, design & selection : PEDS","url":"https://pubmed.ncbi.nlm.nih.gov/31120120","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["peptidyl-prolyl cis-trans isomerase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9213,"output_tokens":1389,"usd":0.024237,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6247,"output_tokens":2570,"usd":0.047743,"stage2_stop_reason":"end_turn"},"total_usd":0.07198,"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\": 1994,\n      \"finding\": \"Peptidyl-prolyl cis-trans isomerase (PPIase) activity was detected in P. falciparum extracts; this activity was completely inhibited by cyclosporin A at concentrations above 0.1 µM but not by FK506 or rapamycin, indicating it is attributable to cyclophilin(s), not FKBPs. Additionally, the P. falciparum cyclophilin-containing extract, in combination with cyclosporin A, inhibited the protein phosphatase activity of bovine calcineurin in vitro.\",\n      \"method\": \"In vitro PPIase activity assay on P. falciparum cell-free extracts; in vitro calcineurin phosphatase inhibition assay with parasite extract plus cyclosporin A\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro enzymatic assay with inhibitor panel, single lab, but activity attributed to unresolved cyclophilin mixture in crude extract, not specifically to PF3D7_1313300\",\n      \"pmids\": [\"7520696\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Among 8 recombinantly expressed P. falciparum cyclophilin family members, only two displayed PPIase (isomerase) activity, while all eight displayed molecular chaperone activity as measured by prevention of thermal aggregation of model substrates. PF3D7_1313300 is one member of this family assessed in this study; the specific activity profile attributed to each individual member is not distinguished in the abstract beyond this family-level summary.\",\n      \"method\": \"Recombinant protein expression in E. coli; in vitro PPIase activity assay; thermal aggregation prevention chaperone assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — two orthogonal enzymatic assays used, but abstract does not specify which individual cyclophilin family members had PPIase activity versus chaperone-only activity, so specific assignment to PF3D7_1313300 cannot be made\",\n      \"pmids\": [\"22546550\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"All 11 P. falciparum cyclophilin or cyclophilin-like proteins (including PF3D7_1313300) were produced recombinantly with a C-terminal His6 tag in E. coli using an identical expression system; recombinant proteins were assessed by thermal melt assay for correct folding and cyclosporin A binding, enabling family-wide functional comparisons.\",\n      \"method\": \"Recombinant expression and purification in E. coli; thermal melt assay for folding and cyclosporin A binding\",\n      \"journal\": \"Protein expression and purification\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single set of assays (thermal melt), abstract does not report specific binding or folding results for PF3D7_1313300 individually\",\n      \"pmids\": [\"21549842\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Mass spectrometry-based interactome mapping of PP1c (protein phosphatase 1 catalytic subunit) and its inhibitor I2 in P. berghei identified a peptidyl-prolyl cis-trans isomerase (ortholog of PF3D7_1313300) as a candidate interactor of the PP1c/I2 complex in both asexual (schizont) and sexual (gametocyte) stages, suggesting it may be a target of this phosphatase regulatory complex.\",\n      \"method\": \"mCherry-tagged PP1c and I2 affinity pulldown from P. berghei transgenic parasites followed by mass spectrometry\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown-MS method, interaction inferred from co-purification without direct validation of physical interaction with PF3D7_1313300 specifically\",\n      \"pmids\": [\"35162991\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1313300 is a member of the P. falciparum cyclophilin family with putative peptidyl-prolyl cis-trans isomerase and/or molecular chaperone activities (as established for the family by recombinant biochemical assays), cyclosporin A sensitivity has been demonstrated at the family level in parasite extracts, and interactome data from P. berghei suggest it may associate with the PP1c/inhibitor-2 phosphatase regulatory complex; however, no experiment has directly and specifically characterized the enzymatic activity, binding partners, structure, or in-parasite function of PF3D7_1313300 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1313300 is annotated as a member of the Plasmodium falciparum cyclophilin family, a group of putative peptidyl-prolyl cis-trans isomerases and/or molecular chaperones assessed collectively by recombinant biochemistry [#1, #2]. In P. falciparum extracts, cyclophilin-attributable PPIase activity is inhibited by cyclosporin A but not FK506 or rapamycin, and the cyclosporin A-bound cyclophilin fraction inhibits calcineurin phosphatase activity in vitro; however, this activity derives from an unresolved cyclophilin mixture and is not specifically assigned to PF3D7_1313300 [#0]. Across the recombinantly expressed family, only two of eight members showed PPIase activity while all eight showed chaperone activity, but the abstracts do not resolve which activity profile belongs to PF3D7_1313300 individually [#1, #2]. In P. berghei, the ortholog of PF3D7_1313300 was recovered as a candidate interactor of the PP1c/inhibitor-2 phosphatase regulatory complex in both asexual and sexual stages by affinity pulldown-mass spectrometry [#3]. Beyond family-level membership and this single co-purification, no experiment has directly characterized the enzymatic activity, binding partners, structure, or in-parasite function of PF3D7_1313300 itself in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing whether P. falciparum harbors cyclosporin A-sensitive PPIase activity distinguished cyclophilins from FKBPs as the drug-relevant isomerases and linked this activity to calcineurin regulation, but did not resolve which of many cyclophilins was responsible.\",\n      \"evidence\": \"In vitro PPIase assay with an inhibitor panel and a calcineurin phosphatase inhibition assay on P. falciparum cell-free extracts\",\n      \"pmids\": [\"7520696\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Activity attributed to an unresolved cyclophilin mixture, not to PF3D7_1313300 specifically\",\n        \"No demonstration that PF3D7_1313300 contributes to the calcineurin-inhibitory activity\",\n        \"No in-parasite functional assignment\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Recombinant production of all 11 P. falciparum cyclophilin/cyclophilin-like proteins, including PF3D7_1313300, under a uniform system enabled family-wide folding and cyclosporin A binding comparison, but did not report PF3D7_1313300-specific results.\",\n      \"evidence\": \"Recombinant expression and purification in E. coli with thermal melt assays for folding and cyclosporin A binding\",\n      \"pmids\": [\"21549842\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"single lab, single assay type, no individual results reported\",\n      \"gaps\": [\n        \"Abstract does not report specific folding or cyclosporin A binding data for PF3D7_1313300\",\n        \"No enzymatic characterization\",\n        \"No structural model\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Orthogonal PPIase and chaperone assays across eight recombinant family members showed the family is functionally split (isomerase-active minority, chaperone-active majority), but the specific activity of PF3D7_1313300 was not distinguished.\",\n      \"evidence\": \"In vitro PPIase activity assay and thermal aggregation prevention chaperone assay on recombinant proteins\",\n      \"pmids\": [\"22546550\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"abstract does not specify which members had PPIase versus chaperone-only activity, so no assignment to PF3D7_1313300 is possible\",\n      \"gaps\": [\n        \"Whether PF3D7_1313300 is one of the two PPIase-active members is unstated\",\n        \"No substrate identity\",\n        \"No in-parasite validation of chaperone or isomerase role\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Interactome mapping of the PP1c/inhibitor-2 phosphatase complex provided the first candidate physiological context for the PF3D7_1313300 ortholog, placing it near a phosphatase regulatory hub across asexual and sexual stages.\",\n      \"evidence\": \"mCherry-tagged PP1c and I2 affinity pulldown from P. berghei transgenic parasites followed by mass spectrometry\",\n      \"pmids\": [\"35162991\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"single pulldown-MS without reciprocal or direct validation of the interaction with the isomerase\",\n      \"gaps\": [\n        \"Co-purification not validated as a direct physical interaction\",\n        \"Shown for the P. berghei ortholog, not P. falciparum PF3D7_1313300 directly\",\n        \"Functional consequence of the association is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct enzymatic activity, substrates, binding partners, structure, and in-parasite function of PF3D7_1313300 itself remain uncharacterized, as all current evidence is either family-level or from an ortholog co-purification.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No member-specific PPIase or chaperone activity established for PF3D7_1313300\",\n        \"No genetic knockout/knockdown phenotype in either species\",\n        \"No validated direct binding partner for PF3D7_1313300\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003755\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"PP1c/inhibitor-2 phosphatase regulatory complex (candidate interactor, P. berghei ortholog) [#3]\"],\n    \"partners\": [\"PP1c (candidate, via ortholog co-purification) [#3]\", \"inhibitor-2 / I2 (candidate, via ortholog co-purification) [#3]\"],\n    \"other_free_text\": [\n      \"PF3D7_1313300 is a member of the P. falciparum cyclophilin family; no experiment in the corpus assigns member-specific enzymatic, chaperone, structural, or in-parasite functional properties to PF3D7_1313300 itself [#1, #2].\",\n      \"Cyclosporin A-sensitive, FK506/rapamycin-insensitive PPIase activity was demonstrated at the level of P. falciparum extracts (unresolved cyclophilin mixture), not specifically for PF3D7_1313300 [#0].\",\n      \"The PP1c/I2 association is reported for the P. berghei ortholog, not P. falciparum PF3D7_1313300 directly [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1313300","name":null,"product":"peptidyl-prolyl cis-trans isomerase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1411700","name":null,"product":"peptidyl-prolyl cis-trans isomerase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1413900","name":null,"product":"peptidyl-prolyl cis-trans isomerase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}