{"gene":"PF3D7_1237000","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2013,"finding":"P. falciparum SUMO E1-activating enzyme (UBA2/PF3D7_1237000, as part of the E1 heterodimer) interacts with the P. falciparum E2-conjugating enzyme (Ubc9) to support sumoylation of RanGAP1 in vitro; however, in heterologous reactions, P. falciparum E1 failed to interact with human E2 (and vice versa), demonstrating organism-specific E1–E2 binding interfaces. Structural analysis and binding studies identified divergent amino acid residues at the E1–E2 interface responsible for this species specificity.","method":"In vitro sumoylation assay (reconstitution with RanGAP1 as substrate), heterologous cross-species interaction assays, structural/binding studies","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity combined with binding studies and structural analysis in a single study, single lab","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 Ubc9, combined with in silico modeling and mutagenesis of the P. falciparum E1 (UBA2/PF3D7_1237000) surface, identified specific surface residues at the E1–E2 interface that explain species-specific interactions between the P. falciparum SUMO E1 and E2 enzymes versus their human counterparts.","method":"X-ray crystallography (human E1 UFD–Ubc9 complex), in silico modeling, site-directed mutagenesis, in vitro biochemical 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, orthogonal methods","pmids":["26697886"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"A mutation introduced into SUMO-activating enzyme subunit 2 (UBA2/PF3D7_1237000) in P. falciparum conferred high-level resistance to the benzoxaborole AN13762, establishing that UBA2 is functionally involved in the parasite's response to this compound and that alterations in the sumoylation/ubiquitination cascade represent a resistance mechanism.","method":"In vitro drug resistance selection, whole-genome sequencing, introduction of specific mutation into parasites and measurement of IC50","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic introduction of mutation with phenotypic readout (IC50 shift), single lab, single method for the UBA2-specific finding","pmids":["31992618"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Biochemical and biophysical analyses showed that the Pf-SUMO (substrate of UBA2/PF3D7_1237000) can interact with human E2 (Ubc9) in a unidirectional cross-species manner, whereas human SUMO1 failed to interact with Pf-E2, revealing asymmetric species specificity in the pathway that begins with E1 (UBA2) activation of SUMO.","method":"Biochemical interaction assays, biophysical analyses, mutagenesis","journal":"Biophysical journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — findings relate primarily to PfSUMO and Pf-Ubc9, with UBA2/E1 not directly assayed; single lab, single study","pmids":["35331687"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1237000 (UBA2) encodes the large subunit of the SUMO-activating enzyme (E1) in P. falciparum; it forms a functional E1 complex that activates PfSUMO and transfers it to the E2-conjugating enzyme (Ubc9) in a species-specific manner defined by divergent surface residues at the E1–E2 interface, and loss-of-function mutations in UBA2 confer resistance to the benzoxaborole AN13762, implicating the sumoylation pathway in parasite susceptibility to this compound."},"narrative":{"mechanistic_narrative":"PF3D7_1237000 (UBA2) encodes the large subunit of the P. falciparum SUMO-activating (E1) enzyme, functioning as part of the E1 heterodimer that initiates the parasite sumoylation cascade by activating PfSUMO and transferring it to the E2-conjugating enzyme Ubc9 to support substrate sumoylation, demonstrated in vitro with RanGAP1 as substrate [PMID:23943616]. The E1–E2 interaction is species-specific: P. falciparum E1 engages P. falciparum Ubc9 but fails to productively interact with human E2, and reciprocally, a specificity traced by structural analysis and mutagenesis to divergent surface residues at the E1–E2 interface [PMID:23943616, PMID:26697886]. Functionally, a mutation engineered into UBA2 confers high-level resistance to the benzoxaborole AN13762, establishing that UBA2 activity contributes to parasite susceptibility to this compound and that alterations in the sumoylation cascade constitute a resistance mechanism [PMID:31992618]. Beyond its role as the E1 large subunit and its E1–E2 interface specificity, the endogenous substrate repertoire, regulation, and cellular localization of PF3D7_1237000 have not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Established that P. falciparum UBA2, as part of the SUMO E1 heterodimer, activates and transfers SUMO to Ubc9 through a binding interface that is organism-specific rather than universal, revealing a potential selectivity handle distinguishing parasite from host sumoylation.","evidence":"In vitro reconstituted sumoylation assay with RanGAP1 substrate plus heterologous cross-species E1–E2 interaction assays and structural/binding analysis","pmids":["23943616"],"confidence":"High","gaps":["Endogenous parasite substrates beyond the RanGAP1 model reaction not identified","Relative contributions of the E1 large versus small subunit not resolved","Cellular localization and expression timing of UBA2 not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Pinpointed the specific surface residues at the UBA2-containing E1–E2 interface responsible for species-specific enzyme pairing, defining the structural basis for parasite-versus-human selectivity.","evidence":"X-ray crystallography of the human E1 UFD–Ubc9 complex combined with in silico modeling, site-directed mutagenesis of the P. falciparum E1, and in vitro biochemical assays","pmids":["26697886"],"confidence":"High","gaps":["No direct crystal structure of the P. falciparum E1–E2 complex reported","Whether interface residues are exploitable for selective inhibitor design not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Connected UBA2 function to drug response by showing that a UBA2 mutation confers resistance to the benzoxaborole AN13762, implicating the sumoylation pathway in the parasite's compound susceptibility.","evidence":"In vitro resistance selection, whole-genome sequencing, and reintroduction of the specific mutation followed by IC50 measurement","pmids":["31992618"],"confidence":"Medium","gaps":["Mechanism by which the mutation alters AN13762 susceptibility (target engagement vs. pathway flux) not defined","Whether AN13762 directly targets UBA2 not established","Single method for the UBA2-specific resistance finding"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Refined the species-specificity picture by showing asymmetric cross-species compatibility in the pathway UBA2 initiates, with Pf-SUMO able to engage human Ubc9 while human SUMO1 cannot engage Pf-Ubc9.","evidence":"Biochemical interaction and biophysical analyses with mutagenesis, focused on PfSUMO and Pf-Ubc9","pmids":["35331687"],"confidence":"Low","gaps":["UBA2/E1 itself was not directly assayed in this study, so implications for UBA2 activation step are inferential","Directionality of specificity not tested in a fully reconstituted parasite cascade","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The endogenous sumoylation substrates, in-cell regulation, and lifecycle-stage functions of PF3D7_1237000 remain undefined, as does the precise mechanistic basis linking UBA2 activity to benzoxaborole susceptibility.","evidence":"","pmids":[],"confidence":"Low","gaps":["No parasite-wide sumoylation substrate map attributed to UBA2 activity","No structure of the intact P. falciparum E1 heterodimer","No genetic essentiality or knockdown phenotype for UBA2 in the corpus"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SUMO-activating enzyme (E1) heterodimer"],"partners":["PFUBC9 (SUMO E2-CONJUGATING ENZYME)","PFSUMO","RANGAP1 (IN VITRO SUMOYLATION SUBSTRATE)"],"other_free_text":["E1–E2 interaction is species-specific, governed by divergent surface residues at the interface (P. falciparum E1 does not productively engage human E2) [#0, #1]","A UBA2 mutation confers high-level resistance to the benzoxaborole AN13762 [#2]","Cross-species compatibility in the pathway is asymmetric: Pf-SUMO engages human Ubc9 but human SUMO1 does not engage Pf-Ubc9 [#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-activating enzyme subunit 2","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":"19465059","id":"PMC_19465059","title":"A complex of three related membrane proteins is conserved on malarial merozoites.","date":"2009","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19465059","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":8074,"output_tokens":1320,"usd":0.022011,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6192,"output_tokens":2436,"usd":0.04593,"stage2_stop_reason":"end_turn"},"total_usd":0.067941,"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 (UBA2/PF3D7_1237000, as part of the E1 heterodimer) interacts with the P. falciparum E2-conjugating enzyme (Ubc9) to support sumoylation of RanGAP1 in vitro; however, in heterologous reactions, P. falciparum E1 failed to interact with human E2 (and vice versa), demonstrating organism-specific E1–E2 binding interfaces. Structural analysis and binding studies identified divergent amino acid residues at the E1–E2 interface responsible for this species specificity.\",\n      \"method\": \"In vitro sumoylation assay (reconstitution with RanGAP1 as substrate), heterologous cross-species interaction assays, structural/binding studies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity combined with binding studies and structural analysis in a single study, single lab\",\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 Ubc9, combined with in silico modeling and mutagenesis of the P. falciparum E1 (UBA2/PF3D7_1237000) surface, identified specific surface residues at the E1–E2 interface that explain species-specific interactions between the P. falciparum SUMO E1 and E2 enzymes versus their human counterparts.\",\n      \"method\": \"X-ray crystallography (human E1 UFD–Ubc9 complex), in silico modeling, site-directed mutagenesis, in vitro biochemical 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, orthogonal methods\",\n      \"pmids\": [\"26697886\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A mutation introduced into SUMO-activating enzyme subunit 2 (UBA2/PF3D7_1237000) in P. falciparum conferred high-level resistance to the benzoxaborole AN13762, establishing that UBA2 is functionally involved in the parasite's response to this compound and that alterations in the sumoylation/ubiquitination cascade represent a resistance mechanism.\",\n      \"method\": \"In vitro drug resistance selection, whole-genome sequencing, introduction of specific mutation into parasites and measurement of IC50\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic introduction of mutation with phenotypic readout (IC50 shift), single lab, single method for the UBA2-specific finding\",\n      \"pmids\": [\"31992618\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Biochemical and biophysical analyses showed that the Pf-SUMO (substrate of UBA2/PF3D7_1237000) can interact with human E2 (Ubc9) in a unidirectional cross-species manner, whereas human SUMO1 failed to interact with Pf-E2, revealing asymmetric species specificity in the pathway that begins with E1 (UBA2) activation of SUMO.\",\n      \"method\": \"Biochemical interaction assays, biophysical analyses, mutagenesis\",\n      \"journal\": \"Biophysical journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — findings relate primarily to PfSUMO and Pf-Ubc9, with UBA2/E1 not directly assayed; single lab, single study\",\n      \"pmids\": [\"35331687\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1237000 (UBA2) encodes the large subunit of the SUMO-activating enzyme (E1) in P. falciparum; it forms a functional E1 complex that activates PfSUMO and transfers it to the E2-conjugating enzyme (Ubc9) in a species-specific manner defined by divergent surface residues at the E1–E2 interface, and loss-of-function mutations in UBA2 confer resistance to the benzoxaborole AN13762, implicating the sumoylation pathway in parasite susceptibility to this compound.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1237000 (UBA2) encodes the large subunit of the P. falciparum SUMO-activating (E1) enzyme, functioning as part of the E1 heterodimer that initiates the parasite sumoylation cascade by activating PfSUMO and transferring it to the E2-conjugating enzyme Ubc9 to support substrate sumoylation, demonstrated in vitro with RanGAP1 as substrate [#0]. The E1\\u2013E2 interaction is species-specific: P. falciparum E1 engages P. falciparum Ubc9 but fails to productively interact with human E2, and reciprocally, a specificity traced by structural analysis and mutagenesis to divergent surface residues at the E1\\u2013E2 interface [#0, #1]. Functionally, a mutation engineered into UBA2 confers high-level resistance to the benzoxaborole AN13762, establishing that UBA2 activity contributes to parasite susceptibility to this compound and that alterations in the sumoylation cascade constitute a resistance mechanism [#2]. Beyond its role as the E1 large subunit and its E1\\u2013E2 interface specificity, the endogenous substrate repertoire, regulation, and cellular localization of PF3D7_1237000 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that P. falciparum UBA2, as part of the SUMO E1 heterodimer, activates and transfers SUMO to Ubc9 through a binding interface that is organism-specific rather than universal, revealing a potential selectivity handle distinguishing parasite from host sumoylation.\",\n      \"evidence\": \"In vitro reconstituted sumoylation assay with RanGAP1 substrate plus heterologous cross-species E1\\u2013E2 interaction assays and structural/binding analysis\",\n      \"pmids\": [\"23943616\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Endogenous parasite substrates beyond the RanGAP1 model reaction not identified\",\n        \"Relative contributions of the E1 large versus small subunit not resolved\",\n        \"Cellular localization and expression timing of UBA2 not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Pinpointed the specific surface residues at the UBA2-containing E1\\u2013E2 interface responsible for species-specific enzyme pairing, defining the structural basis for parasite-versus-human selectivity.\",\n      \"evidence\": \"X-ray crystallography of the human E1 UFD\\u2013Ubc9 complex combined with in silico modeling, site-directed mutagenesis of the P. falciparum E1, and in vitro biochemical assays\",\n      \"pmids\": [\"26697886\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No direct crystal structure of the P. falciparum E1\\u2013E2 complex reported\",\n        \"Whether interface residues are exploitable for selective inhibitor design not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected UBA2 function to drug response by showing that a UBA2 mutation confers resistance to the benzoxaborole AN13762, implicating the sumoylation pathway in the parasite's compound susceptibility.\",\n      \"evidence\": \"In vitro resistance selection, whole-genome sequencing, and reintroduction of the specific mutation followed by IC50 measurement\",\n      \"pmids\": [\"31992618\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which the mutation alters AN13762 susceptibility (target engagement vs. pathway flux) not defined\",\n        \"Whether AN13762 directly targets UBA2 not established\",\n        \"Single method for the UBA2-specific resistance finding\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Refined the species-specificity picture by showing asymmetric cross-species compatibility in the pathway UBA2 initiates, with Pf-SUMO able to engage human Ubc9 while human SUMO1 cannot engage Pf-Ubc9.\",\n      \"evidence\": \"Biochemical interaction and biophysical analyses with mutagenesis, focused on PfSUMO and Pf-Ubc9\",\n      \"pmids\": [\"35331687\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"UBA2/E1 itself was not directly assayed in this study, so implications for UBA2 activation step are inferential\",\n        \"Directionality of specificity not tested in a fully reconstituted parasite cascade\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous sumoylation substrates, in-cell regulation, and lifecycle-stage functions of PF3D7_1237000 remain undefined, as does the precise mechanistic basis linking UBA2 activity to benzoxaborole susceptibility.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No parasite-wide sumoylation substrate map attributed to UBA2 activity\",\n        \"No structure of the intact P. falciparum E1 heterodimer\",\n        \"No genetic essentiality or knockdown phenotype for UBA2 in the corpus\"\n      ],\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:0016874\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016925\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"complexes\": [\n      \"SUMO-activating enzyme (E1) heterodimer\"\n    ],\n    \"partners\": [\n      \"PfUbc9 (SUMO E2-conjugating enzyme)\",\n      \"PfSUMO\",\n      \"RanGAP1 (in vitro sumoylation substrate)\"\n    ],\n    \"other_free_text\": [\n      \"E1\\u2013E2 interaction is species-specific, governed by divergent surface residues at the interface (P. falciparum E1 does not productively engage human E2) [#0, #1]\",\n      \"A UBA2 mutation confers high-level resistance to the benzoxaborole AN13762 [#2]\",\n      \"Cross-species compatibility in the pathway is asymmetric: Pf-SUMO engages human Ubc9 but human SUMO1 does not engage Pf-Ubc9 [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1237000","name":null,"product":"SUMO-activating enzyme subunit 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1451600","name":null,"product":"SUMO-activating enzyme subunit 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1456700","name":null,"product":"SUMO-activating enzyme subunit 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"UBA2","evaluation":null}