{"gene":"PF3D7_1442000","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":1996,"finding":"Recombinant P. falciparum ARF1 (PF3D7_1442000) was purified with stoichiometric amounts of bound GDP; it bound GTP with first-order kinetics (apparent rate constant k' = 0.0145 min⁻¹) and stimulated cholera-toxin-catalyzed ADP-ribosyltransferase activity in a reaction dependent on dimyristoylglycerophosphocholine and cholate, confirming it is a functional class I ARF GTPase. No intrinsic GTPase activity was detected.","method":"Recombinant protein expression in E. coli, GTP-binding assay, cholera-toxin ADP-ribosyltransferase stimulation assay","journal":"European journal of biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution with multiple functional assays (GTP binding, ADP-ribosyltransferase stimulation) in a single focused study","pmids":["8954160"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Recombinant P. falciparum ARF1 activates the unique P. falciparum PIP5K (a bifunctional phosphatidylinositol 4-phosphate 5-kinase) in vitro, whereas phosphatidic acid does not, placing PfARF1 upstream of PtdIns(4,5)P₂ synthesis in the parasite.","method":"In vitro kinase activation assay with recombinant proteins","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution assay, single lab, single method","pmids":["19171150"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"The crystal structure of P. falciparum ARF1 (PF3D7_1442000) was determined in the GDP-bound conformation at 2.5 Å resolution, revealing structural similarity to mammalian class I ARF1s.","method":"X-ray crystallography","journal":"Acta crystallographica. Section F, Structural biology and crystallization communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — atomic-resolution crystal structure with functional-state annotation (GDP-bound), single focused study","pmids":["21045287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PfARF1 localizes to a Golgi compartment in P. falciparum blood-stage parasites, consistent with its N-myristoylation. When a chimeric protein carrying the PfARF1 N-terminus plus the additional palmitoylation and lysine-cluster motifs from PfAK2 was expressed, it was retargeted to the parasite plasma membrane but was not translocated into the parasitophorous vacuole, demonstrating that N-myristoylation alone is insufficient for PVM targeting.","method":"GFP-fusion live fluorescence microscopy, chimeric protein analysis, co-localization with Golgi marker","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging with Golgi marker co-localization plus chimeric construct dissection, single lab","pmids":["25909331"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PfARF1 was co-immunoprecipitated with PfRab5b and co-localizes with PfRab5b adjacent to the ER in early erythrocytic stage parasites. Super-resolution microscopy showed PfARF1 localizes to a distinct ER subdomain from PfRab1b. Expression of an inactive PfARF1 mutant specifically inhibited trafficking of the non-PEXEL protein PfAK2 to the parasitophorous vacuole membrane and also decreased export of the PEXEL-positive protein Rifin, placing PfARF1 at an ER exit step that sorts PfAK2 into the PV pathway and cooperates with PfRab1b in Rifin export.","method":"Co-immunoprecipitation, mass spectrometry, super-resolution immunofluorescence microscopy, active/inactive GTPase mutant expression","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP + MS identification, genetic (dominant mutant) approach with defined trafficking phenotype, single lab","pmids":["33604307"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum ARF1 (PF3D7_1442000) is a GDP/GTP-binding small GTPase of the class I ARF family that localizes to a Golgi/ER-proximal compartment, where it acts at an ER exit step to sort the non-PEXEL cargo PfAK2 into the parasitophorous vacuole pathway and cooperates with PfRab1b in PEXEL-protein (Rifin) export; it also activates the parasite's unique PIP5K in vitro, linking it to PtdIns(4,5)P₂ synthesis, and its GDP-bound structure has been solved at 2.5 Å."},"narrative":{"mechanistic_narrative":"PF3D7_1442000 is a functional class I ADP-ribosylation factor (ARF1) of Plasmodium falciparum that acts as a GDP/GTP-binding small GTPase governing early secretory trafficking in blood-stage parasites [PMID:8954160, PMID:33604307]. Recombinant PfARF1 purifies with stoichiometrically bound GDP, exchanges GDP for GTP with first-order kinetics, and stimulates cholera-toxin-catalyzed ADP-ribosyltransferase activity in a phospholipid-dependent reaction, confirming its identity as a functional ARF; no intrinsic GTPase activity was detected [PMID:8954160]. Its GDP-bound crystal structure at 2.5 Å shows the fold is conserved with mammalian class I ARF1s [PMID:21045287]. Consistent with its N-myristoylation, PfARF1 localizes to a Golgi/ER-proximal compartment, occupying an ER subdomain distinct from PfRab1b and co-localizing with (and co-immunoprecipitating) PfRab5b [PMID:25909331, PMID:33604307]. At this ER exit step it sorts the non-PEXEL cargo PfAK2 into the parasitophorous-vacuole pathway and cooperates with PfRab1b in export of the PEXEL protein Rifin, since an inactive GTPase mutant blocks PfAK2 trafficking and reduces Rifin export [PMID:33604307]. In vitro, PfARF1 activates the parasite's unique bifunctional PIP5K, linking it to PtdIns(4,5)P₂ synthesis [PMID:19171150]. Beyond these secretory and lipid-signaling roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":1996,"claim":"Establishing whether the P. falciparum ARF1 gene product is a bona fide functional GTPase was the first step in assigning it to the class I ARF family.","evidence":"Recombinant expression in E. coli with GTP-binding kinetics and cholera-toxin ADP-ribosyltransferase stimulation assays","pmids":["8954160"],"confidence":"High","gaps":["No intrinsic GTPase activity detected, so the GAP/GEF regulators are unidentified","No cellular localization or trafficking role addressed in vitro"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Testing whether PfARF1 feeds into parasite lipid signaling revealed it as an upstream activator of the unique PfPIP5K, connecting the GTPase to PtdIns(4,5)P2 synthesis.","evidence":"In vitro kinase activation assay with recombinant PfARF1 and PfPIP5K","pmids":["19171150"],"confidence":"Medium","gaps":["Single lab, single in vitro method; not confirmed in cellular context","Physiological consequence of PtdIns(4,5)P2 output not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Solving the GDP-bound structure provided an atomic framework confirming conservation of the class I ARF fold in the parasite.","evidence":"X-ray crystallography of PfARF1 at 2.5 Å","pmids":["21045287"],"confidence":"High","gaps":["Only the GDP-bound (inactive) state captured; no GTP-bound/active conformation","No structure of complexes with effectors or regulators"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Localizing PfARF1 to a Golgi compartment and dissecting membrane-targeting signals clarified which motifs govern its subcellular positioning and distinguished it from cargo it traffics.","evidence":"GFP-fusion live microscopy, Golgi-marker co-localization, and PfARF1/PfAK2 chimeric construct analysis","pmids":["25909331"],"confidence":"Medium","gaps":["Single lab imaging study","N-myristoylation shown insufficient for PVM targeting, but the sufficient signal set unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Placing PfARF1 at an ER exit step and defining its trafficking partners established its role in sorting non-PEXEL cargo and cooperating in PEXEL-protein export.","evidence":"Reciprocal Co-IP/MS with PfRab5b, super-resolution microscopy versus PfRab1b, and inactive-GTPase-mutant trafficking phenotypes for PfAK2 and Rifin","pmids":["33604307"],"confidence":"Medium","gaps":["Single lab; dominant-mutant approach rather than direct loss-of-function","Mechanistic basis of cargo selectivity between PV and export pathways unresolved","Functional significance of the PfRab5b interaction not dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PfARF1 nucleotide cycling is regulated in vivo, and how its GTPase, lipid-kinase-activating, and cargo-sorting activities are integrated, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No GEF/GAP identified for PfARF1","No GTP-bound structure or effector-bound structure","Direct essentiality and loss-of-function phenotype not established in the corpus"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPIP5K (ACTIVATED IN VITRO) [#1]","PFRAB5B (CO-IP, CO-LOCALIZATION) [#4]","PFRAB1B (DISTINCT ER SUBDOMAIN; COOPERATES IN RIFIN EXPORT) [#4]"],"other_free_text":["N-myristoylated; N-myristoylation alone insufficient for PVM targeting [#3]","Inactive GTPase mutant blocks PfAK2 (non-PEXEL cargo) trafficking to the PVM and reduces export of the PEXEL protein Rifin [#4]","No intrinsic GTPase activity detected in vitro; binds GTP with first-order kinetics [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"8954160","id":"PMC_8954160","title":"Isolation, expression and characterization of the gene for an ADP-ribosylation factor from the human malaria parasite, Plasmodium falciparum.","date":"1996","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8954160","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP-ribosylation factor","ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19171150","id":"PMC_19171150","title":"A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP-ribosylation factor in Plasmodium falciparum.","date":"2009","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19171150","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP-ribosylation factor","ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25909331","id":"PMC_25909331","title":"Alternative Protein Secretion in the Malaria Parasite Plasmodium falciparum.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25909331","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP-ribosylation factor","ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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-ribosylation factor","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-ribosylation factor","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-ribosylation factor","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-ribosylation factor","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":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"33604307","id":"PMC_33604307","title":"Rab5b-Associated Arf1 GTPase Regulates Export of N-Myristoylated Adenylate Kinase 2 From the Endoplasmic Reticulum in Plasmodium falciparum.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33604307","citation_count":7,"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-ribosylation factor","ADP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7681,"output_tokens":1601,"usd":0.023529,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6527,"output_tokens":2706,"usd":0.050142,"stage2_stop_reason":"end_turn"},"total_usd":0.073671,"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\": 1996,\n      \"finding\": \"Recombinant P. falciparum ARF1 (PF3D7_1442000) was purified with stoichiometric amounts of bound GDP; it bound GTP with first-order kinetics (apparent rate constant k' = 0.0145 min⁻¹) and stimulated cholera-toxin-catalyzed ADP-ribosyltransferase activity in a reaction dependent on dimyristoylglycerophosphocholine and cholate, confirming it is a functional class I ARF GTPase. No intrinsic GTPase activity was detected.\",\n      \"method\": \"Recombinant protein expression in E. coli, GTP-binding assay, cholera-toxin ADP-ribosyltransferase stimulation assay\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution with multiple functional assays (GTP binding, ADP-ribosyltransferase stimulation) in a single focused study\",\n      \"pmids\": [\"8954160\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Recombinant P. falciparum ARF1 activates the unique P. falciparum PIP5K (a bifunctional phosphatidylinositol 4-phosphate 5-kinase) in vitro, whereas phosphatidic acid does not, placing PfARF1 upstream of PtdIns(4,5)P₂ synthesis in the parasite.\",\n      \"method\": \"In vitro kinase activation assay with recombinant proteins\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution assay, single lab, single method\",\n      \"pmids\": [\"19171150\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The crystal structure of P. falciparum ARF1 (PF3D7_1442000) was determined in the GDP-bound conformation at 2.5 Å resolution, revealing structural similarity to mammalian class I ARF1s.\",\n      \"method\": \"X-ray crystallography\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology and crystallization communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — atomic-resolution crystal structure with functional-state annotation (GDP-bound), single focused study\",\n      \"pmids\": [\"21045287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PfARF1 localizes to a Golgi compartment in P. falciparum blood-stage parasites, consistent with its N-myristoylation. When a chimeric protein carrying the PfARF1 N-terminus plus the additional palmitoylation and lysine-cluster motifs from PfAK2 was expressed, it was retargeted to the parasite plasma membrane but was not translocated into the parasitophorous vacuole, demonstrating that N-myristoylation alone is insufficient for PVM targeting.\",\n      \"method\": \"GFP-fusion live fluorescence microscopy, chimeric protein analysis, co-localization with Golgi marker\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging with Golgi marker co-localization plus chimeric construct dissection, single lab\",\n      \"pmids\": [\"25909331\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfARF1 was co-immunoprecipitated with PfRab5b and co-localizes with PfRab5b adjacent to the ER in early erythrocytic stage parasites. Super-resolution microscopy showed PfARF1 localizes to a distinct ER subdomain from PfRab1b. Expression of an inactive PfARF1 mutant specifically inhibited trafficking of the non-PEXEL protein PfAK2 to the parasitophorous vacuole membrane and also decreased export of the PEXEL-positive protein Rifin, placing PfARF1 at an ER exit step that sorts PfAK2 into the PV pathway and cooperates with PfRab1b in Rifin export.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, super-resolution immunofluorescence microscopy, active/inactive GTPase mutant expression\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP + MS identification, genetic (dominant mutant) approach with defined trafficking phenotype, single lab\",\n      \"pmids\": [\"33604307\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum ARF1 (PF3D7_1442000) is a GDP/GTP-binding small GTPase of the class I ARF family that localizes to a Golgi/ER-proximal compartment, where it acts at an ER exit step to sort the non-PEXEL cargo PfAK2 into the parasitophorous vacuole pathway and cooperates with PfRab1b in PEXEL-protein (Rifin) export; it also activates the parasite's unique PIP5K in vitro, linking it to PtdIns(4,5)P₂ synthesis, and its GDP-bound structure has been solved at 2.5 Å.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1442000 is a functional class I ADP-ribosylation factor (ARF1) of Plasmodium falciparum that acts as a GDP/GTP-binding small GTPase governing early secretory trafficking in blood-stage parasites [#0, #4]. Recombinant PfARF1 purifies with stoichiometrically bound GDP, exchanges GDP for GTP with first-order kinetics, and stimulates cholera-toxin-catalyzed ADP-ribosyltransferase activity in a phospholipid-dependent reaction, confirming its identity as a functional ARF; no intrinsic GTPase activity was detected [#0]. Its GDP-bound crystal structure at 2.5 \\u00c5 shows the fold is conserved with mammalian class I ARF1s [#2]. Consistent with its N-myristoylation, PfARF1 localizes to a Golgi/ER-proximal compartment, occupying an ER subdomain distinct from PfRab1b and co-localizing with (and co-immunoprecipitating) PfRab5b [#3, #4]. At this ER exit step it sorts the non-PEXEL cargo PfAK2 into the parasitophorous-vacuole pathway and cooperates with PfRab1b in export of the PEXEL protein Rifin, since an inactive GTPase mutant blocks PfAK2 trafficking and reduces Rifin export [#4]. In vitro, PfARF1 activates the parasite's unique bifunctional PIP5K, linking it to PtdIns(4,5)P\\u2082 synthesis [#1]. Beyond these secretory and lipid-signaling roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Establishing whether the P. falciparum ARF1 gene product is a bona fide functional GTPase was the first step in assigning it to the class I ARF family.\",\n      \"evidence\": \"Recombinant expression in E. coli with GTP-binding kinetics and cholera-toxin ADP-ribosyltransferase stimulation assays\",\n      \"pmids\": [\"8954160\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No intrinsic GTPase activity detected, so the GAP/GEF regulators are unidentified\",\n        \"No cellular localization or trafficking role addressed in vitro\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Testing whether PfARF1 feeds into parasite lipid signaling revealed it as an upstream activator of the unique PfPIP5K, connecting the GTPase to PtdIns(4,5)P2 synthesis.\",\n      \"evidence\": \"In vitro kinase activation assay with recombinant PfARF1 and PfPIP5K\",\n      \"pmids\": [\"19171150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single in vitro method; not confirmed in cellular context\",\n        \"Physiological consequence of PtdIns(4,5)P2 output not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Solving the GDP-bound structure provided an atomic framework confirming conservation of the class I ARF fold in the parasite.\",\n      \"evidence\": \"X-ray crystallography of PfARF1 at 2.5 \\u00c5\",\n      \"pmids\": [\"21045287\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Only the GDP-bound (inactive) state captured; no GTP-bound/active conformation\",\n        \"No structure of complexes with effectors or regulators\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Localizing PfARF1 to a Golgi compartment and dissecting membrane-targeting signals clarified which motifs govern its subcellular positioning and distinguished it from cargo it traffics.\",\n      \"evidence\": \"GFP-fusion live microscopy, Golgi-marker co-localization, and PfARF1/PfAK2 chimeric construct analysis\",\n      \"pmids\": [\"25909331\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab imaging study\",\n        \"N-myristoylation shown insufficient for PVM targeting, but the sufficient signal set unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Placing PfARF1 at an ER exit step and defining its trafficking partners established its role in sorting non-PEXEL cargo and cooperating in PEXEL-protein export.\",\n      \"evidence\": \"Reciprocal Co-IP/MS with PfRab5b, super-resolution microscopy versus PfRab1b, and inactive-GTPase-mutant trafficking phenotypes for PfAK2 and Rifin\",\n      \"pmids\": [\"33604307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab; dominant-mutant approach rather than direct loss-of-function\",\n        \"Mechanistic basis of cargo selectivity between PV and export pathways unresolved\",\n        \"Functional significance of the PfRab5b interaction not dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfARF1 nucleotide cycling is regulated in vivo, and how its GTPase, lipid-kinase-activating, and cargo-sorting activities are integrated, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No GEF/GAP identified for PfARF1\",\n        \"No GTP-bound structure or effector-bound structure\",\n        \"Direct essentiality and loss-of-function phenotype not established in the corpus\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005525\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005096\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0005789\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0046488\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfPIP5K (activated in vitro) [#1]\",\n      \"PfRab5b (co-IP, co-localization) [#4]\",\n      \"PfRab1b (distinct ER subdomain; cooperates in Rifin export) [#4]\"\n    ],\n    \"other_free_text\": [\n      \"N-myristoylated; N-myristoylation alone insufficient for PVM targeting [#3]\",\n      \"Inactive GTPase mutant blocks PfAK2 (non-PEXEL cargo) trafficking to the PVM and reduces export of the PEXEL protein Rifin [#4]\",\n      \"No intrinsic GTPase activity detected in vitro; binds GTP with first-order kinetics [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1442000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 5 of 5 cited papers name other catalogue genes (PF3D7_1020900, PF3D7_0816900, PF3D7_0110600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1442000","name":null,"product":"ADP-ribosylation factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1305900","name":null,"product":"ADP-ribosylation factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1240300","name":null,"product":"ADP-ribosylation factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}