{"gene":"PF3D7_1144500","run_date":"2026-09-08T14:19:05","timeline":{"discoveries":[{"year":2013,"finding":"P. falciparum SUMO E1-activating enzyme (which includes AOS1/PF3D7_1144500 as subunit 1) interacts with the E2-conjugating enzyme (Ubc9) to form a functional complex capable of modifying RanGAP1 in vitro. However, in heterologous reactions, P. falciparum E1 failed to interact with human E2 (Ubc9), and P. falciparum E2 failed to interact with human E1, revealing species-specific divergence at the E1–E2 binding interface. Structural analysis, binding studies, and functional assays identified divergent amino acid residues at the E1–E2 interface that define organism-specific interactions.","method":"In vitro sumoylation assay using recombinant P. falciparum E1 and E2 enzymes, heterologous cross-species interaction assays, structural analysis, and binding studies","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with mutagenesis and structural analysis in a single study; single lab but multiple orthogonal methods","pmids":["23943616"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"X-ray crystallography of the human SUMO E1 ubiquitin fold domain in complex with E2 (Ubc9) defined the E1–E2 interface; guided by this structure, in silico modeling, mutagenesis, and in vitro biochemical studies of the P. falciparum SUMO E1 (containing AOS1/PF3D7_1144500) and E2 enzymes identified specific surface residues that explain species-specific interactions and the inability of P. falciparum E1/E2 to cross-react with human counterparts.","method":"X-ray crystallography (human E1 UFD–E2 complex), in silico modeling of P. falciparum E1–E2 interface, site-directed mutagenesis, in vitro biochemical interaction assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure combined with mutagenesis and in vitro functional assays; single lab but three orthogonal methods","pmids":["26697886"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Sumoylation levels (reflecting E1/AOS1-containing pathway activity) peak during mid-stages of the P. falciparum intra-erythrocyte developmental cycle, concomitant with hemoglobin consumption and elevated oxidative stress, indicating a role for the sumoylation pathway in oxidative stress response.","method":"Immunoblot analysis across intra-erythrocyte developmental stages; oxidative stress treatment experiments","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunoblot-based staging and stress assays; single lab, two orthogonal approaches but no direct manipulation of AOS1 itself","pmids":["23943616"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"A mutation in SUMO-activating enzyme subunit 2 (the partner of AOS1 in the E1 heterodimer) introduced into P. falciparum conferred high-level resistance (IC50 1.9–5.0 µM) to benzoxaborole AN13762, placing the E1 sumoylation complex (of which AOS1/PF3D7_1144500 is subunit 1) in the mechanism of action or resistance pathway of this antimalarial compound.","method":"In vitro drug resistance selection, whole-genome sequencing of resistant parasites, introduction of specific mutations by genetic engineering, IC50 determination","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic introduction of resistance mutation with phenotypic readout; finding directly implicates the E1 complex but the mutation is in the partner subunit (SAE2), not AOS1 itself; single study","pmids":["31992618"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1144500 (AOS1) encodes subunit 1 of the P. falciparum SUMO E1-activating enzyme heterodimer; the E1 complex (AOS1 + SAE2) adenylates and activates PfSUMO before transfer to the E2-conjugating enzyme Ubc9, and species-specific divergent surface residues at the E1–E2 interface—identified by crystallography, mutagenesis, and in vitro reconstitution—prevent cross-reactivity with the human SUMO machinery, making this interface a potential target for parasite-specific inhibitors."},"narrative":{"mechanistic_narrative":"PF3D7_1144500 (AOS1) encodes subunit 1 of the Plasmodium falciparum SUMO E1-activating enzyme, which together with SUMO-activating enzyme subunit 2 (SAE2) forms the heterodimeric E1 that initiates the parasite sumoylation cascade by activating PfSUMO for transfer to the E2-conjugating enzyme Ubc9; the reconstituted P. falciparum E1 (containing AOS1) and E2 modify RanGAP1 in vitro [PMID:23943616]. A defining feature of this complex is species-specific divergence at the E1–E2 binding interface: P. falciparum E1 fails to interact with human E2 and vice versa, and structure-guided modeling and mutagenesis pinpointed divergent surface residues that dictate these organism-specific interactions and preclude cross-reactivity with the human machinery [PMID:23943616, PMID:26697886]. At the pathway level, sumoylation activity peaks during mid intra-erythrocytic stages coincident with hemoglobin consumption and oxidative stress, linking the AOS1-containing E1 pathway to the parasite oxidative stress response [PMID:23943616], and a resistance mutation in the partner subunit SAE2 confers benzoxaborole resistance, implicating the E1 sumoylation complex in an antimalarial mechanism-of-action pathway [PMID:31992618]. Beyond its role as an E1 subunit in this heterodimer, no AOS1-specific catalytic or regulatory detail distinct from the complex has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Established that AOS1, as subunit 1 of the P. falciparum SUMO E1, forms a functional activating complex that hands SUMO to the E2 Ubc9, and that this E1–E2 pairing is species-specific rather than interchangeable with human enzymes.","evidence":"In vitro sumoylation of RanGAP1 with recombinant P. falciparum E1 and E2, plus heterologous cross-species interaction assays and structural/binding analysis","pmids":["23943616"],"confidence":"High","gaps":["Does not isolate AOS1's individual contribution to adenylation versus that of SAE2","No in vivo confirmation of the cascade in parasites","Full set of physiological SUMO substrates beyond RanGAP1 unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Placed the AOS1-containing sumoylation pathway in a physiological context by showing its activity peaks at mid intra-erythrocytic stages alongside oxidative stress, implicating it in the stress response.","evidence":"Immunoblot staging of sumoylation across the intra-erythrocyte cycle and oxidative stress treatment experiments","pmids":["23943616"],"confidence":"Medium","gaps":["AOS1 itself was not directly manipulated—readout is global sumoylation","Causal role of AOS1 in stress protection not tested","Downstream sumoylated targets during stress not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Resolved the molecular basis of species specificity by using a human E1 UFD–E2 crystal structure to guide modeling and mutagenesis of the P. falciparum E1–E2 interface, identifying surface residues that define parasite-specific interactions and non-cross-reactivity.","evidence":"X-ray crystallography of the human E1 UFD–E2 complex, in silico modeling of the P. falciparum interface, site-directed mutagenesis, and in vitro interaction assays","pmids":["26697886"],"confidence":"High","gaps":["No experimental crystal structure of the P. falciparum E1 (AOS1) itself","Which residues reside on AOS1 versus SAE2 not fully partitioned","Interface residues not yet validated as druggable in cellular assays"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Connected the E1 sumoylation complex to antimalarial pharmacology by showing that a mutation in the partner subunit SAE2 confers high-level benzoxaborole resistance.","evidence":"In vitro resistance selection, whole-genome sequencing, engineered introduction of the SAE2 mutation, and IC50 determination","pmids":["31992618"],"confidence":"Medium","gaps":["Resistance mutation is in SAE2, not AOS1—AOS1's own role in drug action untested","Mechanism by which the mutation confers resistance not defined","Whether the compound directly targets the E1 complex not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what distinguishes AOS1's catalytic and regulatory contribution from the E1 heterodimer as a whole, and whether AOS1 is genetically essential or directly druggable in the parasite.","evidence":"","pmids":[],"confidence":"Low","gaps":["No AOS1-specific loss-of-function or essentiality data","No standalone structure of AOS1","Full SUMO substrate repertoire unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SUMO-activating enzyme E1 heterodimer (AOS1 + SAE2)"],"partners":["SUMO-ACTIVATING ENZYME SUBUNIT 2 (SAE2)","SUMO-CONJUGATING ENZYME E2 (UBC9)","PFSUMO","RANGAP1 (IN VITRO SUBSTRATE)"],"other_free_text":["AOS1 is subunit 1 of the P. falciparum SUMO E1; the corpus characterizes it primarily through the E1 heterodimer and E1–E2 complex rather than as an independently dissected protein.","Species-specific divergent residues at the E1–E2 interface prevent cross-reactivity with the human SUMO machinery, proposed as a parasite-selective inhibitor target [#0, #1].","The SAE2-linked benzoxaborole resistance finding implicates the E1 complex in antimalarial mechanism-of-action, but the resistance mutation lies in the partner subunit, not AOS1 [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21930698","id":"PMC_21930698","title":"Unraveling the ubiquitome of the human malaria parasite.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21930698","citation_count":67,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18547337","id":"PMC_18547337","title":"Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments.","date":"2008","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18547337","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO","PfSUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21700207","id":"PMC_21700207","title":"Functional characterization of a SUMO deconjugating protease of Plasmodium falciparum using newly identified small molecule inhibitors.","date":"2011","source":"Chemistry & biology","url":"https://pubmed.ncbi.nlm.nih.gov/21700207","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31992618","id":"PMC_31992618","title":"Plasmodium falciparum Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/31992618","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23943616","id":"PMC_23943616","title":"Identification of biochemically distinct properties of the small ubiquitin-related modifier (SUMO) conjugation pathway in Plasmodium falciparum.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23943616","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26697886","id":"PMC_26697886","title":"Characterization and Structural Insights into Selective E1-E2 Interactions in the Human and Plasmodium falciparum SUMO Conjugation Systems.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26697886","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34178724","id":"PMC_34178724","title":"Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34178724","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO","PfSUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27631812","id":"PMC_27631812","title":"Detection of SUMOylation in Plasmodium falciparum.","date":"2016","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/27631812","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO","PfSUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27699617","id":"PMC_27699617","title":"Backbone and side-chain resonance assignments of Plasmodium falciparum SUMO.","date":"2016","source":"Biomolecular NMR assignments","url":"https://pubmed.ncbi.nlm.nih.gov/27699617","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO","PfSUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35331687","id":"PMC_35331687","title":"Implications of critical node-dependent unidirectional cross-talk of Plasmodium SUMO pathway proteins.","date":"2022","source":"Biophysical journal","url":"https://pubmed.ncbi.nlm.nih.gov/35331687","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SUMO","PfSUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7750,"output_tokens":1403,"usd":0.022148,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6344,"output_tokens":2522,"usd":0.047385,"stage2_stop_reason":"end_turn"},"total_usd":0.069533,"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\": 2013,\n      \"finding\": \"P. falciparum SUMO E1-activating enzyme (which includes AOS1/PF3D7_1144500 as subunit 1) interacts with the E2-conjugating enzyme (Ubc9) to form a functional complex capable of modifying RanGAP1 in vitro. However, in heterologous reactions, P. falciparum E1 failed to interact with human E2 (Ubc9), and P. falciparum E2 failed to interact with human E1, revealing species-specific divergence at the E1–E2 binding interface. Structural analysis, binding studies, and functional assays identified divergent amino acid residues at the E1–E2 interface that define organism-specific interactions.\",\n      \"method\": \"In vitro sumoylation assay using recombinant P. falciparum E1 and E2 enzymes, heterologous cross-species interaction assays, structural analysis, and binding studies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with mutagenesis and structural analysis in a single study; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"23943616\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"X-ray crystallography of the human SUMO E1 ubiquitin fold domain in complex with E2 (Ubc9) defined the E1–E2 interface; guided by this structure, in silico modeling, mutagenesis, and in vitro biochemical studies of the P. falciparum SUMO E1 (containing AOS1/PF3D7_1144500) and E2 enzymes identified specific surface residues that explain species-specific interactions and the inability of P. falciparum E1/E2 to cross-react with human counterparts.\",\n      \"method\": \"X-ray crystallography (human E1 UFD–E2 complex), in silico modeling of P. falciparum E1–E2 interface, site-directed mutagenesis, in vitro biochemical interaction assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure combined with mutagenesis and in vitro functional assays; single lab but three orthogonal methods\",\n      \"pmids\": [\"26697886\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Sumoylation levels (reflecting E1/AOS1-containing pathway activity) peak during mid-stages of the P. falciparum intra-erythrocyte developmental cycle, concomitant with hemoglobin consumption and elevated oxidative stress, indicating a role for the sumoylation pathway in oxidative stress response.\",\n      \"method\": \"Immunoblot analysis across intra-erythrocyte developmental stages; oxidative stress treatment experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunoblot-based staging and stress assays; single lab, two orthogonal approaches but no direct manipulation of AOS1 itself\",\n      \"pmids\": [\"23943616\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A mutation in SUMO-activating enzyme subunit 2 (the partner of AOS1 in the E1 heterodimer) introduced into P. falciparum conferred high-level resistance (IC50 1.9–5.0 µM) to benzoxaborole AN13762, placing the E1 sumoylation complex (of which AOS1/PF3D7_1144500 is subunit 1) in the mechanism of action or resistance pathway of this antimalarial compound.\",\n      \"method\": \"In vitro drug resistance selection, whole-genome sequencing of resistant parasites, introduction of specific mutations by genetic engineering, IC50 determination\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic introduction of resistance mutation with phenotypic readout; finding directly implicates the E1 complex but the mutation is in the partner subunit (SAE2), not AOS1 itself; single study\",\n      \"pmids\": [\"31992618\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1144500 (AOS1) encodes subunit 1 of the P. falciparum SUMO E1-activating enzyme heterodimer; the E1 complex (AOS1 + SAE2) adenylates and activates PfSUMO before transfer to the E2-conjugating enzyme Ubc9, and species-specific divergent surface residues at the E1–E2 interface—identified by crystallography, mutagenesis, and in vitro reconstitution—prevent cross-reactivity with the human SUMO machinery, making this interface a potential target for parasite-specific inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1144500 (AOS1) encodes subunit 1 of the Plasmodium falciparum SUMO E1-activating enzyme, which together with SUMO-activating enzyme subunit 2 (SAE2) forms the heterodimeric E1 that initiates the parasite sumoylation cascade by activating PfSUMO for transfer to the E2-conjugating enzyme Ubc9; the reconstituted P. falciparum E1 (containing AOS1) and E2 modify RanGAP1 in vitro [#0]. A defining feature of this complex is species-specific divergence at the E1–E2 binding interface: P. falciparum E1 fails to interact with human E2 and vice versa, and structure-guided modeling and mutagenesis pinpointed divergent surface residues that dictate these organism-specific interactions and preclude cross-reactivity with the human machinery [#0, #1]. At the pathway level, sumoylation activity peaks during mid intra-erythrocytic stages coincident with hemoglobin consumption and oxidative stress, linking the AOS1-containing E1 pathway to the parasite oxidative stress response [#2], and a resistance mutation in the partner subunit SAE2 confers benzoxaborole resistance, implicating the E1 sumoylation complex in an antimalarial mechanism-of-action pathway [#3]. Beyond its role as an E1 subunit in this heterodimer, no AOS1-specific catalytic or regulatory detail distinct from the complex has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that AOS1, as subunit 1 of the P. falciparum SUMO E1, forms a functional activating complex that hands SUMO to the E2 Ubc9, and that this E1–E2 pairing is species-specific rather than interchangeable with human enzymes.\",\n      \"evidence\": \"In vitro sumoylation of RanGAP1 with recombinant P. falciparum E1 and E2, plus heterologous cross-species interaction assays and structural/binding analysis\",\n      \"pmids\": [\"23943616\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not isolate AOS1's individual contribution to adenylation versus that of SAE2\", \"No in vivo confirmation of the cascade in parasites\", \"Full set of physiological SUMO substrates beyond RanGAP1 unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed the AOS1-containing sumoylation pathway in a physiological context by showing its activity peaks at mid intra-erythrocytic stages alongside oxidative stress, implicating it in the stress response.\",\n      \"evidence\": \"Immunoblot staging of sumoylation across the intra-erythrocyte cycle and oxidative stress treatment experiments\",\n      \"pmids\": [\"23943616\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"AOS1 itself was not directly manipulated—readout is global sumoylation\", \"Causal role of AOS1 in stress protection not tested\", \"Downstream sumoylated targets during stress not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Resolved the molecular basis of species specificity by using a human E1 UFD–E2 crystal structure to guide modeling and mutagenesis of the P. falciparum E1–E2 interface, identifying surface residues that define parasite-specific interactions and non-cross-reactivity.\",\n      \"evidence\": \"X-ray crystallography of the human E1 UFD–E2 complex, in silico modeling of the P. falciparum interface, site-directed mutagenesis, and in vitro interaction assays\",\n      \"pmids\": [\"26697886\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No experimental crystal structure of the P. falciparum E1 (AOS1) itself\", \"Which residues reside on AOS1 versus SAE2 not fully partitioned\", \"Interface residues not yet validated as druggable in cellular assays\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected the E1 sumoylation complex to antimalarial pharmacology by showing that a mutation in the partner subunit SAE2 confers high-level benzoxaborole resistance.\",\n      \"evidence\": \"In vitro resistance selection, whole-genome sequencing, engineered introduction of the SAE2 mutation, and IC50 determination\",\n      \"pmids\": [\"31992618\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Resistance mutation is in SAE2, not AOS1—AOS1's own role in drug action untested\", \"Mechanism by which the mutation confers resistance not defined\", \"Whether the compound directly targets the E1 complex not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what distinguishes AOS1's catalytic and regulatory contribution from the E1 heterodimer as a whole, and whether AOS1 is genetically essential or directly druggable in the parasite.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No AOS1-specific loss-of-function or essentiality data\", \"No standalone structure of AOS1\", \"Full SUMO substrate repertoire unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019948\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008641\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016925\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0006979\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"SUMO-activating enzyme E1 heterodimer (AOS1 + SAE2)\"],\n    \"partners\": [\"SUMO-activating enzyme subunit 2 (SAE2)\", \"SUMO-conjugating enzyme E2 (Ubc9)\", \"PfSUMO\", \"RanGAP1 (in vitro substrate)\"],\n    \"other_free_text\": [\n      \"AOS1 is subunit 1 of the P. falciparum SUMO E1; the corpus characterizes it primarily through the E1 heterodimer and E1–E2 complex rather than as an independently dissected protein.\",\n      \"Species-specific divergent residues at the E1–E2 interface prevent cross-reactivity with the human SUMO machinery, proposed as a parasite-selective inhibitor target [#0, #1].\",\n      \"The SAE2-linked benzoxaborole resistance finding implicates the E1 complex in antimalarial mechanism-of-action, but the resistance mutation lies in the partner subunit, not AOS1 [#3].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1144500","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_0505800, PF3D7_0709700, PF3D7_1438500). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1144500","name":null,"product":"SUMO-activating enzyme subunit 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0904500","name":null,"product":"SUMO-activating enzyme subunit 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0942400","name":null,"product":"SUMO-activating enzyme subunit 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AOS1","evaluation":null}