{"gene":"PF3D7_0915100","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2013,"finding":"P. falciparum E2-conjugating enzyme (UBC9/PF3D7_0915100) interacts with the P. falciparum E1-activating enzyme to recognize and modify RanGAP1 in vitro; however, in heterologous reactions, P. falciparum UBC9 failed to interact with the human E1 enzyme to support RanGAP1 modification, demonstrating organism-specific E1-E2 binding selectivity.","method":"In vitro sumoylation assay, binding studies, structural analysis, mutagenesis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with mutagenesis and structural analysis, 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 human Ubc9 defined the E1-E2 interface; guided by this structure, in silico modeling, mutagenesis, and in vitro biochemical studies of P. falciparum SUMO E1 and UBC9 (PF3D7_0915100) identified divergent surface residues that explain species-specific E1-E2 interactions and confer selective inhibitor potential.","method":"X-ray crystallography, in silico modeling, mutagenesis, in vitro biochemical assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure of related complex with mutagenesis and in vitro biochemical validation applied to Pf UBC9, multiple orthogonal methods in single study","pmids":["26697886"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Biochemical and biophysical analyses showed that critical residues at the N-terminus of P. falciparum UBC9 (PF3D7_0915100) are responsible for diminished interaction with human SUMO1; mutating these residues to corresponding human Ubc9 residues restored electrostatic, π-π, and hydrophobic interactions and allowed efficient cross-species SUMO-UBC9 interaction, demonstrating that these surface-accessible residues act as specificity nodes.","method":"Biochemical and biophysical binding assays, site-directed mutagenesis","journal":"Biophysical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — mutagenesis with biophysical binding assays, single lab, single study","pmids":["35331687"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Knockdown/insufficiency of host cell Ubc9/E2 (the sole SUMO-conjugating enzyme in the host) promoted P. berghei exoerythrocytic form (EEF) growth in hepatocytes, while SUMO1 overexpression was detrimental to EEF growth, placing host-cell UBC9-mediated SUMOylation as a restriction factor for parasite liver-stage development.","method":"Genetic manipulation (overexpression and knockdown of host Ubc9/SUMO1) with quantitative measurement of EEF growth, transcriptomic analysis","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function with defined cellular phenotype, but this concerns the HOST cell UBC9 rather than the parasite UBC9 (PF3D7_0915100); single lab, single study — finding attributed to host Ubc9, not parasite UBC9","pmids":["28078755"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"Selection of P. falciparum for high-level resistance to benzoxaborole AN13762 yielded parasites with mutations in genes encoding ubiquitination/sumoylation cascade enzymes, including SUMO-activating enzyme subunit 2; introduction of a SUMO-activating enzyme subunit 2 mutation conferred similar high-level resistance, implicating the sumoylation pathway (upstream of UBC9) as a mechanism of resistance.","method":"In vitro resistance selection, whole-genome sequencing, introduction of specific mutations, IC50 measurement","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic evidence implicates the sumoylation pathway broadly but does not directly interrogate UBC9/PF3D7_0915100 itself; single lab","pmids":["31992618"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum UBC9 (PF3D7_0915100) is the sole SUMO E2-conjugating enzyme of the parasite sumoylation pathway; it functions together with the P. falciparum E1-activating enzyme to transfer SUMO to target proteins, but displays organism-specific selectivity at the E1-E2 binding interface — defined by divergent surface residues (particularly at the UBC9 N-terminus) — that prevents functional cross-interaction with human E1, making this interface a candidate target for parasite-specific inhibitors."},"narrative":{"mechanistic_narrative":"PF3D7_0915100 (UBC9) is the P. falciparum SUMO E2-conjugating enzyme of the parasite sumoylation pathway, acting together with the parasite SUMO E1-activating enzyme to recognize and transfer SUMO to substrate proteins, as demonstrated by in vitro sumoylation of RanGAP1 [PMID:23943616]. A defining feature of the parasite enzyme is organism-specific selectivity at protein-protein interfaces: P. falciparum UBC9 fails to interact functionally with the human E1 enzyme, and structure-guided modeling and mutagenesis localized this specificity to divergent surface residues at the E1-E2 interface [PMID:23943616, PMID:26697886]. Critical residues at the UBC9 N-terminus similarly govern its interaction with SUMO1, and substituting these for the corresponding human Ubc9 residues restored electrostatic, π-π, and hydrophobic contacts and enabled efficient cross-species SUMO-UBC9 binding, establishing these surface-accessible residues as specificity nodes and candidate parasite-selective inhibitor sites [PMID:35331687]. Beyond its role as the E2 enzyme and the mapping of its interaction interfaces, the parasite substrate repertoire and cellular functions of PF3D7_0915100 have not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing whether P. falciparum encodes a functional SUMO E2 enzyme and whether it could engage host machinery answered a basic question about the parasite sumoylation pathway and its druggability.","evidence":"in vitro sumoylation and binding assays with structural analysis and mutagenesis, using P. falciparum E1, UBC9, and RanGAP1 substrate","pmids":["23943616"],"confidence":"High","gaps":["Full parasite substrate repertoire beyond RanGAP1 not defined","No in vivo demonstration of UBC9 function in the parasite","Structural basis of E1-E2 selectivity not yet resolved at atomic level"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Defining the E1-E2 interface at structural resolution answered why the parasite and human enzymes do not cross-react and pinpointed exploitable divergent residues.","evidence":"X-ray crystallography of human SUMO E1 UFD-Ubc9 complex, guiding in silico modeling, mutagenesis, and in vitro biochemistry of P. falciparum SUMO E1 and UBC9","pmids":["26697886"],"confidence":"High","gaps":["Interface residues mapped by modeling rather than a parasite-specific crystal structure","Inhibitor selectivity claim not experimentally validated with actual compounds"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Identifying the N-terminal residues that weaken UBC9-SUMO1 binding answered which specific surface nodes drive species-specificity and confirmed they are engineerable.","evidence":"biochemical and biophysical binding assays with site-directed mutagenesis converting P. falciparum UBC9 residues to human equivalents","pmids":["35331687"],"confidence":"Medium","gaps":["Single lab, single study without independent confirmation","Consequences of these residues for downstream substrate modification in vivo untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Resistance selection against a benzoxaborole implicated the sumoylation cascade in drug response, but the evidence points to the SUMO-activating enzyme upstream rather than UBC9 itself.","evidence":"in vitro resistance selection, whole-genome sequencing, and mutation reintroduction with IC50 measurement in P. falciparum","pmids":["31992618"],"confidence":"Low","gaps":["Does not directly interrogate UBC9/PF3D7_0915100","Mechanistic link between sumoylation pathway and drug action unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The full parasite substrate set, in-cell function across the life cycle, and validated parasite-selective inhibition of PF3D7_0915100 remain unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic characterization of UBC9 in P. falciparum stages","No parasite substrate atlas beyond RanGAP1","No confirmed inhibitor exploiting the divergent interface"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["P. FALCIPARUM SUMO E1-ACTIVATING ENZYME","SUMO1","RANGAP1 (SUBSTRATE)"],"other_free_text":["PF3D7_0915100 is the P. falciparum SUMO E2-conjugating enzyme acting downstream of the parasite E1-activating enzyme [#0].","Species-specific E1-E2 and SUMO-UBC9 interaction selectivity is governed by divergent surface residues, particularly at the UBC9 N-terminus, and is proposed as a parasite-selective inhibitor target [#1, #2].","Discovery #3 concerns HOST-cell Ubc9 in P. berghei liver-stage restriction and does not describe parasite PF3D7_0915100.","Discovery #4 implicates the sumoylation pathway (SUMO-activating enzyme subunit 2) in benzoxaborole resistance but does not directly interrogate UBC9."]}},"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":["UBC9","SUMO"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28078755","id":"PMC_28078755","title":"Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii.","date":"2017","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28078755","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["UBC9"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","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":"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":["UBC9","SUMO","PfSUMO","PfUBC9"],"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8164,"output_tokens":1558,"usd":0.023931,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6591,"output_tokens":2263,"usd":0.044765,"stage2_stop_reason":"end_turn"},"total_usd":0.068696,"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\": 2013,\n      \"finding\": \"P. falciparum E2-conjugating enzyme (UBC9/PF3D7_0915100) interacts with the P. falciparum E1-activating enzyme to recognize and modify RanGAP1 in vitro; however, in heterologous reactions, P. falciparum UBC9 failed to interact with the human E1 enzyme to support RanGAP1 modification, demonstrating organism-specific E1-E2 binding selectivity.\",\n      \"method\": \"In vitro sumoylation assay, binding studies, structural analysis, mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with mutagenesis and structural analysis, 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 human Ubc9 defined the E1-E2 interface; guided by this structure, in silico modeling, mutagenesis, and in vitro biochemical studies of P. falciparum SUMO E1 and UBC9 (PF3D7_0915100) identified divergent surface residues that explain species-specific E1-E2 interactions and confer selective inhibitor potential.\",\n      \"method\": \"X-ray crystallography, in silico modeling, mutagenesis, in vitro biochemical assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure of related complex with mutagenesis and in vitro biochemical validation applied to Pf UBC9, multiple orthogonal methods in single study\",\n      \"pmids\": [\"26697886\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Biochemical and biophysical analyses showed that critical residues at the N-terminus of P. falciparum UBC9 (PF3D7_0915100) are responsible for diminished interaction with human SUMO1; mutating these residues to corresponding human Ubc9 residues restored electrostatic, π-π, and hydrophobic interactions and allowed efficient cross-species SUMO-UBC9 interaction, demonstrating that these surface-accessible residues act as specificity nodes.\",\n      \"method\": \"Biochemical and biophysical binding assays, site-directed mutagenesis\",\n      \"journal\": \"Biophysical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — mutagenesis with biophysical binding assays, single lab, single study\",\n      \"pmids\": [\"35331687\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Knockdown/insufficiency of host cell Ubc9/E2 (the sole SUMO-conjugating enzyme in the host) promoted P. berghei exoerythrocytic form (EEF) growth in hepatocytes, while SUMO1 overexpression was detrimental to EEF growth, placing host-cell UBC9-mediated SUMOylation as a restriction factor for parasite liver-stage development.\",\n      \"method\": \"Genetic manipulation (overexpression and knockdown of host Ubc9/SUMO1) with quantitative measurement of EEF growth, transcriptomic analysis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function with defined cellular phenotype, but this concerns the HOST cell UBC9 rather than the parasite UBC9 (PF3D7_0915100); single lab, single study — finding attributed to host Ubc9, not parasite UBC9\",\n      \"pmids\": [\"28078755\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Selection of P. falciparum for high-level resistance to benzoxaborole AN13762 yielded parasites with mutations in genes encoding ubiquitination/sumoylation cascade enzymes, including SUMO-activating enzyme subunit 2; introduction of a SUMO-activating enzyme subunit 2 mutation conferred similar high-level resistance, implicating the sumoylation pathway (upstream of UBC9) as a mechanism of resistance.\",\n      \"method\": \"In vitro resistance selection, whole-genome sequencing, introduction of specific mutations, IC50 measurement\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic evidence implicates the sumoylation pathway broadly but does not directly interrogate UBC9/PF3D7_0915100 itself; single lab\",\n      \"pmids\": [\"31992618\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum UBC9 (PF3D7_0915100) is the sole SUMO E2-conjugating enzyme of the parasite sumoylation pathway; it functions together with the P. falciparum E1-activating enzyme to transfer SUMO to target proteins, but displays organism-specific selectivity at the E1-E2 binding interface — defined by divergent surface residues (particularly at the UBC9 N-terminus) — that prevents functional cross-interaction with human E1, making this interface a candidate target for parasite-specific inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0915100 (UBC9) is the P. falciparum SUMO E2-conjugating enzyme of the parasite sumoylation pathway, acting together with the parasite SUMO E1-activating enzyme to recognize and transfer SUMO to substrate proteins, as demonstrated by in vitro sumoylation of RanGAP1 [#0]. A defining feature of the parasite enzyme is organism-specific selectivity at protein-protein interfaces: P. falciparum UBC9 fails to interact functionally with the human E1 enzyme, and structure-guided modeling and mutagenesis localized this specificity to divergent surface residues at the E1-E2 interface [#0, #1]. Critical residues at the UBC9 N-terminus similarly govern its interaction with SUMO1, and substituting these for the corresponding human Ubc9 residues restored electrostatic, π-π, and hydrophobic contacts and enabled efficient cross-species SUMO-UBC9 binding, establishing these surface-accessible residues as specificity nodes and candidate parasite-selective inhibitor sites [#2]. Beyond its role as the E2 enzyme and the mapping of its interaction interfaces, the parasite substrate repertoire and cellular functions of PF3D7_0915100 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether P. falciparum encodes a functional SUMO E2 enzyme and whether it could engage host machinery answered a basic question about the parasite sumoylation pathway and its druggability.\",\n      \"evidence\": \"in vitro sumoylation and binding assays with structural analysis and mutagenesis, using P. falciparum E1, UBC9, and RanGAP1 substrate\",\n      \"pmids\": [\"23943616\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full parasite substrate repertoire beyond RanGAP1 not defined\", \"No in vivo demonstration of UBC9 function in the parasite\", \"Structural basis of E1-E2 selectivity not yet resolved at atomic level\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defining the E1-E2 interface at structural resolution answered why the parasite and human enzymes do not cross-react and pinpointed exploitable divergent residues.\",\n      \"evidence\": \"X-ray crystallography of human SUMO E1 UFD-Ubc9 complex, guiding in silico modeling, mutagenesis, and in vitro biochemistry of P. falciparum SUMO E1 and UBC9\",\n      \"pmids\": [\"26697886\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Interface residues mapped by modeling rather than a parasite-specific crystal structure\", \"Inhibitor selectivity claim not experimentally validated with actual compounds\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identifying the N-terminal residues that weaken UBC9-SUMO1 binding answered which specific surface nodes drive species-specificity and confirmed they are engineerable.\",\n      \"evidence\": \"biochemical and biophysical binding assays with site-directed mutagenesis converting P. falciparum UBC9 residues to human equivalents\",\n      \"pmids\": [\"35331687\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single study without independent confirmation\", \"Consequences of these residues for downstream substrate modification in vivo untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resistance selection against a benzoxaborole implicated the sumoylation cascade in drug response, but the evidence points to the SUMO-activating enzyme upstream rather than UBC9 itself.\",\n      \"evidence\": \"in vitro resistance selection, whole-genome sequencing, and mutation reintroduction with IC50 measurement in P. falciparum\",\n      \"pmids\": [\"31992618\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Does not directly interrogate UBC9/PF3D7_0915100\", \"Mechanistic link between sumoylation pathway and drug action unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The full parasite substrate set, in-cell function across the life cycle, and validated parasite-selective inhibition of PF3D7_0915100 remain unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genetic characterization of UBC9 in P. falciparum stages\", \"No parasite substrate atlas beyond RanGAP1\", \"No confirmed inhibitor exploiting the divergent interface\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061656\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019789\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016925\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"P. falciparum SUMO E1-activating enzyme\", \"SUMO1\", \"RanGAP1 (substrate)\"],\n    \"other_free_text\": [\n      \"PF3D7_0915100 is the P. falciparum SUMO E2-conjugating enzyme acting downstream of the parasite E1-activating enzyme [#0].\",\n      \"Species-specific E1-E2 and SUMO-UBC9 interaction selectivity is governed by divergent surface residues, particularly at the UBC9 N-terminus, and is proposed as a parasite-selective inhibitor target [#1, #2].\",\n      \"Discovery #3 concerns HOST-cell Ubc9 in P. berghei liver-stage restriction and does not describe parasite PF3D7_0915100.\",\n      \"Discovery #4 implicates the sumoylation pathway (SUMO-activating enzyme subunit 2) in benzoxaborole resistance but does not directly interrogate UBC9.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0915100","name":null,"product":"SUMO-conjugating enzyme UBC9","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0816100","name":null,"product":"SUMO-conjugating enzyme UBC9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"UBC9","evaluation":null}