{"gene":"PF3D7_0526200","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2011,"finding":"The crystal structure of the catalytic domain of P. falciparum ARFGAP (PF3D7_0526200) was determined at 2.4 Å resolution by MAD phasing using the Zn2+ ion bound at the zinc-finger domain. The overall fold is similar to mammalian ARFGAPs, but several residues in the ARF1-interaction interface and at the crystal dimer interface are unique to the P. falciparum protein.","method":"X-ray crystallography (MAD phasing, 2.4 Å resolution)","journal":"Acta crystallographica. Section F, Structural biology and crystallization communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with experimental phasing; single study but direct structural determination with functional annotation of active-site residues","pmids":["22102228"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"The GAP domains of both P. falciparum ArfGAPs (including the one corresponding to PF3D7_0526200) stimulate GTP hydrolysis by PfArf1 in vitro with activity equivalent to that of human ArfGAP1, but are insensitive to the human ArfGAP inhibitor QS11. A novel compound inhibited one of the P. falciparum GAP domains with IC50 4.7 µM, demonstrating selectivity between the two parasite ArfGAPs.","method":"In vitro colorimetric microtiter plate-based GTPase activity assay; compound inhibition profiling","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay establishing catalytic activity, but the paper studies two P. falciparum ArfGAPs and does not always distinguish which GAP domain corresponds to PF3D7_0526200; single lab, single method","pmids":["32144363"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0526200 (ARFGAP2) encodes a P. falciparum ADP-ribosylation factor GTPase-activating protein whose catalytic domain adopts a zinc-finger-dependent fold similar to mammalian ARFGAPs but with distinctive residues at the ARF1-interaction interface; in vitro, its GAP domain stimulates GTP hydrolysis by PfArf1 with efficiency comparable to human ArfGAP1 yet insensitive to the human inhibitor QS11, placing it as a deactivator of PfArf1 in the parasite vesicular trafficking pathway."},"narrative":{"mechanistic_narrative":"PF3D7_0526200 (ARFGAP2) encodes a Plasmodium falciparum ADP-ribosylation factor GTPase-activating protein that functions as a deactivator of the parasite small GTPase PfArf1. Its catalytic domain adopts a fold similar to mammalian ARFGAPs and depends on a Zn2+ ion coordinated at a zinc-finger domain, but carries residues unique to the P. falciparum protein at the ARF1-interaction interface and at the crystal dimer interface [PMID:22102228]. In vitro, the GAP domain stimulates GTP hydrolysis by PfArf1 with efficiency equivalent to human ArfGAP1 yet is insensitive to the human ArfGAP inhibitor QS11, and a distinct compound distinguishes it enzymatically from the parasite's other ArfGAP [PMID:32144363]. Beyond this structural and in vitro catalytic characterization, the cellular role, trafficking context, and in vivo function of PF3D7_0526200 have not been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Whether the parasite ARFGAP encoded by PF3D7_0526200 shares the architecture of mammalian ARFGAPs was unknown; solving its catalytic-domain structure established a zinc-finger-dependent fold with parasite-specific interface residues.","evidence":"X-ray crystallography of the catalytic domain by MAD phasing at 2.4 Å using the bound Zn2+ ion","pmids":["22102228"],"confidence":"High","gaps":["Structure is of the isolated catalytic domain, not the full-length protein","No co-structure with PfArf1 to define the interaction interface experimentally","Functional consequence of the parasite-unique residues not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether the PF3D7_0526200 GAP domain is catalytically active and pharmacologically distinct was unknown; in vitro assays showed it stimulates PfArf1 GTP hydrolysis at human-ArfGAP1-equivalent efficiency but is insensitive to QS11, and compound profiling demonstrated selectivity between the two parasite ArfGAPs.","evidence":"In vitro colorimetric microtiter GTPase activity assay and compound inhibition profiling","pmids":["32144363"],"confidence":"Medium","gaps":["The study analyzes two P. falciparum ArfGAPs and does not always resolve which GAP domain corresponds to PF3D7_0526200","Activity shown in vitro only, not in parasites","The identity of the selectively inhibited GAP domain relative to PF3D7_0526200 is not fully established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The cellular localization, trafficking pathway membership, in vivo function, and essentiality of PF3D7_0526200 in the parasite remain unaddressed in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No cellular localization data for PF3D7_0526200","No genetic knockout or knockdown phenotype","No demonstration of PfArf1 regulation in living parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFARF1 (TARGET GTPASE WHOSE GTP HYDROLYSIS IS STIMULATED BY THE PF3D7_0526200 GAP DOMAIN) [#1]"],"other_free_text":["Catalytic domain adopts a zinc-finger-dependent fold similar to mammalian ARFGAPs, with parasite-unique residues at the ARF1-interaction interface [#0]","GAP activity is insensitive to the human ArfGAP inhibitor QS11 [#1]","A compound inhibits one of the two P. falciparum ArfGAP domains with IC50 4.7 µM, demonstrating selectivity between the two parasite ArfGAPs [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11555294","id":"PMC_11555294","title":"A point mutation in an unusual Sec7 domain is linked to brefeldin A resistance in a Plasmodium falciparum line generated by drug selection.","date":"2001","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11555294","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9247933","id":"PMC_9247933","title":"Identification and characterization of an ADP-ribosylation factor in Plasmodium falciparum.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9247933","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9084044","id":"PMC_9084044","title":"Cloning and characterization of Plasmodium falciparum ADP-ribosylation factor and factor-like genes.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9084044","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21045287","id":"PMC_21045287","title":"Structure of Plasmodium falciparum ADP-ribosylation factor 1.","date":"2010","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/21045287","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15500915","id":"PMC_15500915","title":"Double cross-over gene replacement within the sec 7 domain of a GDP-GTP exchange factor from Plasmodium falciparum allows the generation of a transgenic brefeldin A-resistant parasite line.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15500915","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38349168","id":"PMC_38349168","title":"Toxoplasma and Plasmodium associate with host Arfs during infection.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/38349168","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"32144363","id":"PMC_32144363","title":"Detection of the in vitro modulation of Plasmodium falciparum Arf1 by Sec7 and ArfGAP domains using a colorimetric plate-based assay.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32144363","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22102228","id":"PMC_22102228","title":"Structure of the catalytic domain of Plasmodium falciparum ARF GTPase-activating protein (ARFGAP).","date":"2011","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/22102228","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5814,"output_tokens":766,"usd":0.014466,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5442,"output_tokens":1697,"usd":0.034818,"stage2_stop_reason":"end_turn"},"total_usd":0.049284,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"The crystal structure of the catalytic domain of P. falciparum ARFGAP (PF3D7_0526200) was determined at 2.4 Å resolution by MAD phasing using the Zn2+ ion bound at the zinc-finger domain. The overall fold is similar to mammalian ARFGAPs, but several residues in the ARF1-interaction interface and at the crystal dimer interface are unique to the P. falciparum protein.\",\n      \"method\": \"X-ray crystallography (MAD phasing, 2.4 Å resolution)\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology and crystallization communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with experimental phasing; single study but direct structural determination with functional annotation of active-site residues\",\n      \"pmids\": [\"22102228\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The GAP domains of both P. falciparum ArfGAPs (including the one corresponding to PF3D7_0526200) stimulate GTP hydrolysis by PfArf1 in vitro with activity equivalent to that of human ArfGAP1, but are insensitive to the human ArfGAP inhibitor QS11. A novel compound inhibited one of the P. falciparum GAP domains with IC50 4.7 µM, demonstrating selectivity between the two parasite ArfGAPs.\",\n      \"method\": \"In vitro colorimetric microtiter plate-based GTPase activity assay; compound inhibition profiling\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay establishing catalytic activity, but the paper studies two P. falciparum ArfGAPs and does not always distinguish which GAP domain corresponds to PF3D7_0526200; single lab, single method\",\n      \"pmids\": [\"32144363\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0526200 (ARFGAP2) encodes a P. falciparum ADP-ribosylation factor GTPase-activating protein whose catalytic domain adopts a zinc-finger-dependent fold similar to mammalian ARFGAPs but with distinctive residues at the ARF1-interaction interface; in vitro, its GAP domain stimulates GTP hydrolysis by PfArf1 with efficiency comparable to human ArfGAP1 yet insensitive to the human inhibitor QS11, placing it as a deactivator of PfArf1 in the parasite vesicular trafficking pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0526200 (ARFGAP2) encodes a Plasmodium falciparum ADP-ribosylation factor GTPase-activating protein that functions as a deactivator of the parasite small GTPase PfArf1. Its catalytic domain adopts a fold similar to mammalian ARFGAPs and depends on a Zn2+ ion coordinated at a zinc-finger domain, but carries residues unique to the P. falciparum protein at the ARF1-interaction interface and at the crystal dimer interface [#0]. In vitro, the GAP domain stimulates GTP hydrolysis by PfArf1 with efficiency equivalent to human ArfGAP1 yet is insensitive to the human ArfGAP inhibitor QS11, and a distinct compound distinguishes it enzymatically from the parasite's other ArfGAP [#1]. Beyond this structural and in vitro catalytic characterization, the cellular role, trafficking context, and in vivo function of PF3D7_0526200 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether the parasite ARFGAP encoded by PF3D7_0526200 shares the architecture of mammalian ARFGAPs was unknown; solving its catalytic-domain structure established a zinc-finger-dependent fold with parasite-specific interface residues.\",\n      \"evidence\": \"X-ray crystallography of the catalytic domain by MAD phasing at 2.4 Å using the bound Zn2+ ion\",\n      \"pmids\": [\"22102228\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure is of the isolated catalytic domain, not the full-length protein\",\n        \"No co-structure with PfArf1 to define the interaction interface experimentally\",\n        \"Functional consequence of the parasite-unique residues not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether the PF3D7_0526200 GAP domain is catalytically active and pharmacologically distinct was unknown; in vitro assays showed it stimulates PfArf1 GTP hydrolysis at human-ArfGAP1-equivalent efficiency but is insensitive to QS11, and compound profiling demonstrated selectivity between the two parasite ArfGAPs.\",\n      \"evidence\": \"In vitro colorimetric microtiter GTPase activity assay and compound inhibition profiling\",\n      \"pmids\": [\"32144363\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The study analyzes two P. falciparum ArfGAPs and does not always resolve which GAP domain corresponds to PF3D7_0526200\",\n        \"Activity shown in vitro only, not in parasites\",\n        \"The identity of the selectively inhibited GAP domain relative to PF3D7_0526200 is not fully established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cellular localization, trafficking pathway membership, in vivo function, and essentiality of PF3D7_0526200 in the parasite remain unaddressed in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No cellular localization data for PF3D7_0526200\",\n        \"No genetic knockout or knockdown phenotype\",\n        \"No demonstration of PfArf1 regulation in living parasites\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005096\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfArf1 (target GTPase whose GTP hydrolysis is stimulated by the PF3D7_0526200 GAP domain) [#1]\"],\n    \"other_free_text\": [\n      \"Catalytic domain adopts a zinc-finger-dependent fold similar to mammalian ARFGAPs, with parasite-unique residues at the ARF1-interaction interface [#0]\",\n      \"GAP activity is insensitive to the human ArfGAP inhibitor QS11 [#1]\",\n      \"A compound inhibits one of the two P. falciparum ArfGAP domains with IC50 4.7 µM, demonstrating selectivity between the two parasite ArfGAPs [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0526200","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_1020900, PF3D7_1244600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0526200","name":null,"product":"ADP-ribosylation factor GTPase-activating protein 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1241000","name":null,"product":"ADP-ribosylation factor GTPase-activating protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1006600","name":null,"product":"ADP-ribosylation factor GTPase-activating protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ARFGAP2","evaluation":null}