{"gene":"PF3D7_0909300","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2006,"finding":"PfARP (PF3D7_0909300 / Gene ID PFI0450c) was cloned, overexpressed, and purified as a recombinant protein with a minimum subunit MW of ~24 kDa. CD analysis revealed secondary structure composition of 61% alpha-helix and 15% beta-sheet. Semiquantitative RT-PCR showed expression at both ring and trophozoite stages, with immunofluorescence microscopy demonstrating highest expression at trophozoite stage and very little in schizont stage. Subcellular fractionation/immunofluorescence established that PfARP is a cytosolic protein.","method":"RT-PCR, recombinant protein overexpression and purification, SDS-PAGE, CD spectroscopy, immunofluorescence microscopy","journal":"Protein expression and purification","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal methods (RT-PCR, immunofluorescence, CD) in a single lab; localization established but no functional consequence demonstrated","pmids":["17182255"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Bilirubin-induced oxidative stress in P. falciparum up-regulated the expression of apoptosis-related protein PfARP (Gene ID PFI0450c), concurrent with induction of caspase-like protease activity and reduction of mitochondrial membrane potential, suggesting PfARP is responsive to pro-apoptotic stimuli in the parasite.","method":"RT-PCR/expression analysis under bilirubin treatment, measurement of lipid peroxide, glutathione, H2O2, hydroxyl radical, mitochondrial membrane potential assay, caspase-like protease activity assay","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method for PfARP expression (upregulation observed but no direct functional experiment on PfARP itself)","pmids":["18070610"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfARP (PF3D7_0909300) is a cytosolic ~24 kDa protein expressed predominantly at the trophozoite stage of P. falciparum, with alpha-helical secondary structure, whose expression is upregulated in response to bilirubin-induced oxidative stress alongside caspase-like protease activation and loss of mitochondrial membrane potential, implicating it in parasite cell death signaling; its precise molecular function remains unknown."},"narrative":{"mechanistic_narrative":"PfARP (PF3D7_0909300), designated an apoptosis-related protein of P. falciparum, is a cytosolic protein of ~24 kDa subunit mass with a predominantly alpha-helical secondary structure (61% alpha-helix, 15% beta-sheet by CD), expressed at ring and trophozoite stages with highest abundance at the trophozoite stage and minimal expression in schizonts [PMID:17182255]. Its expression is up-regulated by bilirubin-induced oxidative stress, concurrent with induction of caspase-like protease activity and loss of mitochondrial membrane potential, linking it to pro-apoptotic stress responses in the parasite [PMID:18070610]. Beyond this stress-responsive expression profile and its cytosolic localization, no direct molecular function, binding partner, or substrate of PfARP has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing whether PfARP is a real, folded protein and where it resides addressed the basic question of its physical identity and cellular compartment, prerequisites for any functional model.","evidence":"recombinant overexpression, purification, CD spectroscopy, RT-PCR and immunofluorescence in P. falciparum","pmids":["17182255"],"confidence":"Medium","gaps":["no molecular activity or biochemical function demonstrated","no interacting partners or substrates identified","stage-specific role of cytosolic localization not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Whether PfARP responds to death-inducing stimuli was tested by monitoring its expression under oxidative stress, connecting the protein to a candidate parasite cell-death pathway.","evidence":"expression analysis under bilirubin treatment alongside caspase-like protease and mitochondrial membrane potential assays in P. falciparum","pmids":["18070610"],"confidence":"Low","gaps":["only expression up-regulation observed, with no direct functional or loss-of-function experiment on PfARP itself","causal role of PfARP in the caspase-like/mitochondrial cascade not established","no evidence PfARP acts within, rather than merely correlates with, the death response"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular activity of PfARP and its mechanistic position in parasite cell-death signaling remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["no biochemical activity, substrate, or binding partner identified","no genetic loss-of-function or rescue linking PfARP to a phenotype","no structural model beyond secondary-structure composition"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["~24 kDa recombinant subunit; 61% alpha-helix, 15% beta-sheet by CD [#0]","Expressed at ring and trophozoite stages, peaking at trophozoite stage, minimal in schizonts [#0]","Expression up-regulated by bilirubin-induced oxidative stress, concurrent with caspase-like protease activation and loss of mitochondrial membrane potential [#1]","Precise molecular function of PF3D7_0909300 remains uncharacterized in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18070610","id":"PMC_18070610","title":"Bilirubin inhibits Plasmodium falciparum growth through the generation of reactive oxygen species.","date":"2007","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/18070610","citation_count":60,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PFI0450c","apoptosis-related protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2421257","id":"PMC_2421257","title":"An asparagine-rich protein from blood stages of Plasmodium falciparum shares determinants with sporozoites.","date":"1986","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2421257","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28454546","id":"PMC_28454546","title":"Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/28454546","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26348884","id":"PMC_26348884","title":"In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.","date":"2015","source":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/26348884","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17182255","id":"PMC_17182255","title":"Overexpression, purification and localization of apoptosis related protein from Plasmodium falciparum.","date":"2006","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/17182255","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PFI0450c","apoptosis-related protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23688042","id":"PMC_23688042","title":"Characterizing PvARP, a novel Plasmodium vivax antigen.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/23688042","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41128014","id":"PMC_41128014","title":"Extreme Genetic Diversity and Signatures of Balancing Selection in Plasmodium vivax Blood-Stage Antigens.","date":"2026","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/41128014","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6275,"output_tokens":745,"usd":0.015,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5351,"output_tokens":1519,"usd":0.032365,"stage2_stop_reason":"end_turn"},"total_usd":0.047365,"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\": 2006,\n      \"finding\": \"PfARP (PF3D7_0909300 / Gene ID PFI0450c) was cloned, overexpressed, and purified as a recombinant protein with a minimum subunit MW of ~24 kDa. CD analysis revealed secondary structure composition of 61% alpha-helix and 15% beta-sheet. Semiquantitative RT-PCR showed expression at both ring and trophozoite stages, with immunofluorescence microscopy demonstrating highest expression at trophozoite stage and very little in schizont stage. Subcellular fractionation/immunofluorescence established that PfARP is a cytosolic protein.\",\n      \"method\": \"RT-PCR, recombinant protein overexpression and purification, SDS-PAGE, CD spectroscopy, immunofluorescence microscopy\",\n      \"journal\": \"Protein expression and purification\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal methods (RT-PCR, immunofluorescence, CD) in a single lab; localization established but no functional consequence demonstrated\",\n      \"pmids\": [\"17182255\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Bilirubin-induced oxidative stress in P. falciparum up-regulated the expression of apoptosis-related protein PfARP (Gene ID PFI0450c), concurrent with induction of caspase-like protease activity and reduction of mitochondrial membrane potential, suggesting PfARP is responsive to pro-apoptotic stimuli in the parasite.\",\n      \"method\": \"RT-PCR/expression analysis under bilirubin treatment, measurement of lipid peroxide, glutathione, H2O2, hydroxyl radical, mitochondrial membrane potential assay, caspase-like protease activity assay\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method for PfARP expression (upregulation observed but no direct functional experiment on PfARP itself)\",\n      \"pmids\": [\"18070610\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfARP (PF3D7_0909300) is a cytosolic ~24 kDa protein expressed predominantly at the trophozoite stage of P. falciparum, with alpha-helical secondary structure, whose expression is upregulated in response to bilirubin-induced oxidative stress alongside caspase-like protease activation and loss of mitochondrial membrane potential, implicating it in parasite cell death signaling; its precise molecular function remains unknown.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfARP (PF3D7_0909300), designated an apoptosis-related protein of P. falciparum, is a cytosolic protein of ~24 kDa subunit mass with a predominantly alpha-helical secondary structure (61% alpha-helix, 15% beta-sheet by CD), expressed at ring and trophozoite stages with highest abundance at the trophozoite stage and minimal expression in schizonts [#0]. Its expression is up-regulated by bilirubin-induced oxidative stress, concurrent with induction of caspase-like protease activity and loss of mitochondrial membrane potential, linking it to pro-apoptotic stress responses in the parasite [#1]. Beyond this stress-responsive expression profile and its cytosolic localization, no direct molecular function, binding partner, or substrate of PfARP has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing whether PfARP is a real, folded protein and where it resides addressed the basic question of its physical identity and cellular compartment, prerequisites for any functional model.\",\n      \"evidence\": \"recombinant overexpression, purification, CD spectroscopy, RT-PCR and immunofluorescence in P. falciparum\",\n      \"pmids\": [\n        \"17182255\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no molecular activity or biochemical function demonstrated\",\n        \"no interacting partners or substrates identified\",\n        \"stage-specific role of cytosolic localization not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Whether PfARP responds to death-inducing stimuli was tested by monitoring its expression under oxidative stress, connecting the protein to a candidate parasite cell-death pathway.\",\n      \"evidence\": \"expression analysis under bilirubin treatment alongside caspase-like protease and mitochondrial membrane potential assays in P. falciparum\",\n      \"pmids\": [\n        \"18070610\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"only expression up-regulation observed, with no direct functional or loss-of-function experiment on PfARP itself\",\n        \"causal role of PfARP in the caspase-like/mitochondrial cascade not established\",\n        \"no evidence PfARP acts within, rather than merely correlates with, the death response\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of PfARP and its mechanistic position in parasite cell-death signaling remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no biochemical activity, substrate, or binding partner identified\",\n        \"no genetic loss-of-function or rescue linking PfARP to a phenotype\",\n        \"no structural model beyond secondary-structure composition\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005829\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006915\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0006979\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"~24 kDa recombinant subunit; 61% alpha-helix, 15% beta-sheet by CD [#0]\",\n      \"Expressed at ring and trophozoite stages, peaking at trophozoite stage, minimal in schizonts [#0]\",\n      \"Expression up-regulated by bilirubin-induced oxidative stress, concurrent with caspase-like protease activation and loss of mitochondrial membrane potential [#1]\",\n      \"Precise molecular function of PF3D7_0909300 remains uncharacterized in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0909300","name":null,"product":"apoptosis-related protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0810500","name":null,"product":"apoptosis-related protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ARP","evaluation":null}