{"gene":"PF3D7_1348800","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2022,"finding":"PF3D7_1348800 (Pf-E2/Pf-Ubc9) shows unidirectional cross-species interaction: Pf-SUMO interacts with human E2, but human SUMO1 (Hs-SUMO1) fails to interact with Pf-E2. Critical residues at the N-terminus of Pf-E2 are responsible for the diminished Hs-SUMO1/Pf-E2 interaction; mutating these residues to corresponding human Ubc9 residues restores electrostatic, π-π, and hydrophobic interactions and enables efficient cross-species interaction.","method":"Biochemical and biophysical analyses (binding assays, mutagenesis of N-terminal residues)","journal":"Biophysical journal","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — mutagenesis with functional validation of binding, but single lab and single study with abstract-level detail only","pmids":["35331687"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1348800 (Pf-E2/Pf-Ubc9) functions as the E2 SUMO-conjugating enzyme in the P. falciparum SUMOylation pathway, whose N-terminal residues determine species-specific interaction with SUMO proteins, preventing human SUMO1 from engaging Pf-E2 while allowing Pf-SUMO to interact with human E2."},"narrative":{"mechanistic_narrative":"PF3D7_1348800 (referred to here as Pf-E2) functions as the E2 SUMO-conjugating enzyme of the Plasmodium falciparum SUMOylation pathway, where its interaction with SUMO proteins is governed by species-specific determinants at its N-terminus [PMID:35331687]. The cross-species interaction is unidirectional: Pf-SUMO engages human E2, but human SUMO1 fails to interact with Pf-E2, and critical N-terminal residues of Pf-E2 are responsible for this diminished interaction — mutating them to the corresponding human Ubc9 residues restores electrostatic, π-π, and hydrophobic contacts and enables efficient cross-species binding [PMID:35331687]. Beyond this determinant of SUMO recognition [PMID:35331687], no further mechanistic detail on Pf-E2 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"It was unknown why the parasite and human SUMOylation machineries fail to cross-react; this work showed that N-terminal residues of Pf-E2 dictate species-specific SUMO recognition, establishing a molecular basis for a divergent parasite SUMO-conjugating enzyme.","evidence":"Biochemical and biophysical binding assays with N-terminal mutagenesis in P. falciparum Pf-E2","pmids":["35331687"],"confidence":"Medium","gaps":["Single lab, single study with abstract-level detail only","Catalytic SUMO-conjugating activity of Pf-E2 on substrates not directly demonstrated","No structural model or in vivo functional consequence established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether Pf-E2 catalyzes SUMO transfer to specific parasite substrates, its interacting partners in the full SUMOylation cascade, and its role in parasite biology remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No SUMO substrate identified for Pf-E2","E3 ligase or upstream E1 partners not defined in this corpus","Cellular localization and essentiality not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PF-SUMO"],"other_free_text":["N-terminal residues of Pf-E2 confer species-specific SUMO recognition; human SUMO1 fails to interact with Pf-E2 while Pf-SUMO can engage human E2 [#0].","Mutation of Pf-E2 N-terminal residues to human Ubc9 counterparts restores electrostatic, π-π, and hydrophobic interactions and enables cross-species binding [#0]."]}},"prefetch_data":{},"corpus_meta":[{"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":["PfE2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3325,"output_tokens":453,"usd":0.008385,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4947,"output_tokens":1178,"usd":0.027092,"stage2_stop_reason":"end_turn"},"total_usd":0.035477,"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\": 2022,\n      \"finding\": \"PF3D7_1348800 (Pf-E2/Pf-Ubc9) shows unidirectional cross-species interaction: Pf-SUMO interacts with human E2, but human SUMO1 (Hs-SUMO1) fails to interact with Pf-E2. Critical residues at the N-terminus of Pf-E2 are responsible for the diminished Hs-SUMO1/Pf-E2 interaction; mutating these residues to corresponding human Ubc9 residues restores electrostatic, π-π, and hydrophobic interactions and enables efficient cross-species interaction.\",\n      \"method\": \"Biochemical and biophysical analyses (binding assays, mutagenesis of N-terminal residues)\",\n      \"journal\": \"Biophysical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — mutagenesis with functional validation of binding, but single lab and single study with abstract-level detail only\",\n      \"pmids\": [\"35331687\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1348800 (Pf-E2/Pf-Ubc9) functions as the E2 SUMO-conjugating enzyme in the P. falciparum SUMOylation pathway, whose N-terminal residues determine species-specific interaction with SUMO proteins, preventing human SUMO1 from engaging Pf-E2 while allowing Pf-SUMO to interact with human E2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1348800 (referred to here as Pf-E2) functions as the E2 SUMO-conjugating enzyme of the Plasmodium falciparum SUMOylation pathway, where its interaction with SUMO proteins is governed by species-specific determinants at its N-terminus [#0]. The cross-species interaction is unidirectional: Pf-SUMO engages human E2, but human SUMO1 fails to interact with Pf-E2, and critical N-terminal residues of Pf-E2 are responsible for this diminished interaction — mutating them to the corresponding human Ubc9 residues restores electrostatic, π-π, and hydrophobic contacts and enables efficient cross-species binding [#0]. Beyond this determinant of SUMO recognition [#0], no further mechanistic detail on Pf-E2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"It was unknown why the parasite and human SUMOylation machineries fail to cross-react; this work showed that N-terminal residues of Pf-E2 dictate species-specific SUMO recognition, establishing a molecular basis for a divergent parasite SUMO-conjugating enzyme.\",\n      \"evidence\": \"Biochemical and biophysical binding assays with N-terminal mutagenesis in P. falciparum Pf-E2\",\n      \"pmids\": [\"35331687\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study with abstract-level detail only\",\n        \"Catalytic SUMO-conjugating activity of Pf-E2 on substrates not directly demonstrated\",\n        \"No structural model or in vivo functional consequence established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether Pf-E2 catalyzes SUMO transfer to specific parasite substrates, its interacting partners in the full SUMOylation cascade, and its role in parasite biology remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No SUMO substrate identified for Pf-E2\",\n        \"E3 ligase or upstream E1 partners not defined in this corpus\",\n        \"Cellular localization and essentiality not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061656\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016925\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Pf-SUMO\"],\n    \"other_free_text\": [\n      \"N-terminal residues of Pf-E2 confer species-specific SUMO recognition; human SUMO1 fails to interact with Pf-E2 while Pf-SUMO can engage human E2 [#0].\",\n      \"Mutation of Pf-E2 N-terminal residues to human Ubc9 counterparts restores electrostatic, π-π, and hydrophobic interactions and enables cross-species binding [#0].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1348800","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0505800, PF3D7_0915100). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1348800","name":null,"product":"E1-E2 ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1361600","name":null,"product":"E1-E2 ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1252100","name":null,"product":"E1-E2 ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}