{"gene":"PF3D7_1141700","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2017,"finding":"PfOTU (PF3D7_1141700) localizes to vesicular compartments and associates with the apicoplast, as determined by C-terminal regulatable fluorescent affinity tagging of the native protein.","method":"Endogenous C-terminal fluorescent affinity tagging / live imaging / fractionation","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence shown in single lab using fluorescent tagging and knockdown","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Knockdown of PfOTU (PF3D7_1141700) via degradation-tag-mediated conditional depletion causes abnormal apicoplast development, blocks parasite development beyond early-schizont stages, and hinders apicoplast protein import, establishing PfOTU as essential for apicoplast homeostasis.","method":"Degradation-tag-mediated knockdown; apicoplast morphology and protein import assays; isoprenoid precursor rescue experiment","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional KD with multiple orthogonal functional readouts (morphology, protein import, isoprenoid rescue) in a single rigorous study","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PfOTU (PF3D7_1141700) is implicated in membrane deconjugation of Atg8 (lipid-modified Atg8-PE cleavage), suggesting a cysteine protease activity that may be linked to apicoplast protein import.","method":"Knockdown combined with Atg8 membrane association assay; indirect functional evidence","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single indirect assay; deconjugation activity inferred from knockdown phenotype rather than direct in vitro reconstitution","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In P. berghei, Otu (ortholog of PF3D7_1141700) localizes to the apicoplast; individual Otu gene disruption yields no visible blood-stage or mosquito-stage developmental defects, and all mice infected with Otu KO sporozoites became patent, indicating Otu is individually dispensable for these stages.","method":"Genetic knockout; phenotypic analysis across blood, mosquito, and liver stages; fluorescence localization","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with multi-stage phenotypic analysis confirming apicoplast localization; single lab but comprehensive stage coverage","pmids":["37910326"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"In P. berghei, simultaneous deletion of Otu and Atg4 is refractory (lethal), whereas individual deletions are viable, demonstrating that Otu and Atg4 together are essential for parasite survival and that they share redundant Atg8 deconjugation function.","method":"Genetic epistasis — attempted double KO; refractory deletion as synthetic lethality evidence","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via double-KO attempt (synthetic lethality), single lab","pmids":["37910326"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"In P. berghei, Otu cannot fully replace Atg4 function in Atg8 recycling because it cleaves the peptide bond at the N-terminal side of the glycine residue, irreversibly inactivating Atg8 rather than allowing its recycling.","method":"In vitro deconjugation assay combined with analysis of Atg8 cleavage site; comparison of Atg4 KO and Otu KO phenotypes","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro cleavage site determination plus genetic KO comparison; single lab","pmids":["37910326"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"finding":"Plasmodium OTU (including PF3D7_1141700 ortholog) exhibits ubiquitin and ISG15 deconjugation (deubiquitinase) enzymatic activity, demonstrated by reduction of intracellular ubiquitinated protein content in cellular assays.","method":"Deconjugation assay; western blot and flow cytometry for intracellular ubiquitinated proteins; structural modeling of catalytic residues","journal":"The Biochemical journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — deconjugation activity assessed by indirect intracellular content assay rather than direct in vitro reconstitution; single lab; structural modeling computational","pmids":["34486667"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium vivax","strain":""},{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"PF3D7_1141700 (PfOTU) is an apicoplast-associated OTU-domain cysteine protease essential for apicoplast homeostasis and protein import in P. falciparum; it performs Atg8 membrane deconjugation (and has ubiquitin/ISG15 deconjugase activity), but in P. berghei its Atg8-deconjugation function is redundant with Atg4 (the two are synthetically lethal when both deleted), and Otu irreversibly inactivates Atg8 by cleaving N-terminal to glycine rather than releasing it for recycling."},"narrative":{"mechanistic_narrative":"PF3D7_1141700 (PfOTU) is an OTU-domain cysteine protease that localizes to vesicular compartments and associates with the apicoplast in P. falciparum, where it is essential for apicoplast homeostasis [PMID:28423214]. Conditional depletion causes abnormal apicoplast development, arrests parasites beyond the early-schizont stage, and impairs apicoplast protein import, phenotypes consistent with a role in the trafficking machinery that supplies the organelle [PMID:28423214]. Its mechanistic activity centers on Atg8: PfOTU is implicated in deconjugating membrane-bound Atg8 (Atg8-PE cleavage) [PMID:28423214], and across Plasmodium species the enzyme also displays ubiquitin/ISG15 deconjugase activity attributed to its OTU catalytic residues [PMID:34486667]. Species comparison refines this picture: the P. berghei ortholog is individually dispensable at blood, mosquito, and liver stages but is synthetically lethal with Atg4, showing that the two enzymes share a redundant Atg8-deconjugation function; unlike Atg4, Otu cleaves N-terminal to the Atg8 glycine, irreversibly inactivating Atg8 rather than releasing it for recycling [PMID:37910326]. Beyond the apicoplast/Atg8 axis and its deconjugase chemistry, no further mechanistic detail for this gene has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing where PfOTU acts and whether it matters answered whether this OTU-domain protein has an organelle-specific role, placing it at the apicoplast as an essential factor for organelle biogenesis and protein import.","evidence":"Endogenous C-terminal fluorescent tagging with live imaging and fractionation, plus degradation-tag conditional knockdown with apicoplast morphology, protein-import, and isoprenoid-rescue readouts, in P. falciparum","pmids":["28423214"],"confidence":"High","gaps":["Molecular substrate directly linking PfOTU protease activity to protein import not identified in vitro","Mechanism by which loss of PfOTU blocks import versus organelle maintenance not separated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Connecting PfOTU to Atg8 membrane deconjugation proposed the biochemical activity underlying its apicoplast function, linking a cysteine protease to Atg8-PE cleavage.","evidence":"Knockdown combined with Atg8 membrane association assay (indirect functional inference) in P. falciparum","pmids":["28423214"],"confidence":"Low","gaps":["Deconjugation inferred from knockdown phenotype rather than direct in vitro reconstitution","Cleavage specificity and catalytic residues not directly demonstrated in this work"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Demonstrating deconjugase chemistry addressed whether the OTU domain is catalytically active, showing ubiquitin and ISG15 deconjugation activity for Plasmodium OTU.","evidence":"Cellular deconjugation assay with western blot and flow cytometry for intracellular ubiquitinated proteins plus computational modeling of catalytic residues, in P. falciparum, P. vivax, and P. yoelii","pmids":["34486667"],"confidence":"Low","gaps":["Activity measured by indirect intracellular ubiquitin content rather than direct in vitro reconstitution with purified enzyme","Structural placement of catalytic residues is computational, not experimentally solved","Relationship between ubiquitin/ISG15 activity and the apicoplast Atg8 role unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium vivax","strain":""},{"species":"Plasmodium yoelii","strain":""}]},{"year":2023,"claim":"Genetic dissection in P. berghei answered whether Otu is individually essential and how its Atg8 activity relates to Atg4, revealing redundancy via synthetic lethality and a mechanistically distinct, irreversible mode of Atg8 processing.","evidence":"Knockout with multi-stage phenotyping, refractory double-KO (synthetic lethality) with Atg4, and in vitro determination of the Atg8 cleavage site, in P. berghei","pmids":["37910326"],"confidence":"Medium","gaps":["Species divergence: P. berghei Otu is individually dispensable whereas P. falciparum knockdown is lethal for apicoplast development","Why irreversible N-terminal-to-glycine cleavage cannot substitute for Atg4 recycling in vivo not fully resolved","Direct biochemical link between synthetic-lethal Atg8 function and apicoplast import not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether PfOTU's ubiquitin/ISG15 deconjugase activity and its Atg8-deconjugation activity operate on the same or distinct pathways, and which activity underlies the apicoplast protein-import defect, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct in vitro reconstitution of PF3D7_1141700 protease on a defined apicoplast substrate","No structure of the P. falciparum enzyme","The mechanistic reason species differ in individual essentiality is unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ATG8 (DECONJUGATION SUBSTRATE) [#2, #5]","ATG4 (SYNTHETICALLY LETHAL / FUNCTIONALLY REDUNDANT) [#4]"],"other_free_text":["PfOTU (PF3D7_1141700) is essential for apicoplast development, protein import, and progression beyond the early-schizont stage in P. falciparum [#1].","The P. berghei ortholog is individually dispensable across blood, mosquito, and liver stages but essential in combination with Atg4 [#3, #4].","Otu cleaves Atg8 N-terminal to the glycine residue, irreversibly inactivating it rather than enabling recycling, distinguishing it mechanistically from Atg4 [#5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28423214","id":"PMC_28423214","title":"Plasmodium falciparum OTU-like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8.","date":"2017","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28423214","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OTU","PfOTU"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37910326","id":"PMC_37910326","title":"Regulation of Atg8 membrane deconjugation by cysteine proteases in the malaria parasite Plasmodium berghei.","date":"2023","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/37910326","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OTU"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34486667","id":"PMC_34486667","title":"Identification of first-in-class plasmodium OTU inhibitors with potent anti-malarial activity.","date":"2021","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/34486667","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OTU"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4363,"output_tokens":1877,"usd":0.020622,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6959,"output_tokens":2744,"usd":0.051698,"stage2_stop_reason":"end_turn"},"total_usd":0.07232,"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\": 2017,\n      \"finding\": \"PfOTU (PF3D7_1141700) localizes to vesicular compartments and associates with the apicoplast, as determined by C-terminal regulatable fluorescent affinity tagging of the native protein.\",\n      \"method\": \"Endogenous C-terminal fluorescent affinity tagging / live imaging / fractionation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence shown in single lab using fluorescent tagging and knockdown\",\n      \"pmids\": [\"28423214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Knockdown of PfOTU (PF3D7_1141700) via degradation-tag-mediated conditional depletion causes abnormal apicoplast development, blocks parasite development beyond early-schizont stages, and hinders apicoplast protein import, establishing PfOTU as essential for apicoplast homeostasis.\",\n      \"method\": \"Degradation-tag-mediated knockdown; apicoplast morphology and protein import assays; isoprenoid precursor rescue experiment\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KD with multiple orthogonal functional readouts (morphology, protein import, isoprenoid rescue) in a single rigorous study\",\n      \"pmids\": [\"28423214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PfOTU (PF3D7_1141700) is implicated in membrane deconjugation of Atg8 (lipid-modified Atg8-PE cleavage), suggesting a cysteine protease activity that may be linked to apicoplast protein import.\",\n      \"method\": \"Knockdown combined with Atg8 membrane association assay; indirect functional evidence\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single indirect assay; deconjugation activity inferred from knockdown phenotype rather than direct in vitro reconstitution\",\n      \"pmids\": [\"28423214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. berghei, Otu (ortholog of PF3D7_1141700) localizes to the apicoplast; individual Otu gene disruption yields no visible blood-stage or mosquito-stage developmental defects, and all mice infected with Otu KO sporozoites became patent, indicating Otu is individually dispensable for these stages.\",\n      \"method\": \"Genetic knockout; phenotypic analysis across blood, mosquito, and liver stages; fluorescence localization\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with multi-stage phenotypic analysis confirming apicoplast localization; single lab but comprehensive stage coverage\",\n      \"pmids\": [\"37910326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. berghei, simultaneous deletion of Otu and Atg4 is refractory (lethal), whereas individual deletions are viable, demonstrating that Otu and Atg4 together are essential for parasite survival and that they share redundant Atg8 deconjugation function.\",\n      \"method\": \"Genetic epistasis — attempted double KO; refractory deletion as synthetic lethality evidence\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via double-KO attempt (synthetic lethality), single lab\",\n      \"pmids\": [\"37910326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. berghei, Otu cannot fully replace Atg4 function in Atg8 recycling because it cleaves the peptide bond at the N-terminal side of the glycine residue, irreversibly inactivating Atg8 rather than allowing its recycling.\",\n      \"method\": \"In vitro deconjugation assay combined with analysis of Atg8 cleavage site; comparison of Atg4 KO and Otu KO phenotypes\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro cleavage site determination plus genetic KO comparison; single lab\",\n      \"pmids\": [\"37910326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Plasmodium OTU (including PF3D7_1141700 ortholog) exhibits ubiquitin and ISG15 deconjugation (deubiquitinase) enzymatic activity, demonstrated by reduction of intracellular ubiquitinated protein content in cellular assays.\",\n      \"method\": \"Deconjugation assay; western blot and flow cytometry for intracellular ubiquitinated proteins; structural modeling of catalytic residues\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — deconjugation activity assessed by indirect intracellular content assay rather than direct in vitro reconstitution; single lab; structural modeling computational\",\n      \"pmids\": [\"34486667\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium vivax\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1141700 (PfOTU) is an apicoplast-associated OTU-domain cysteine protease essential for apicoplast homeostasis and protein import in P. falciparum; it performs Atg8 membrane deconjugation (and has ubiquitin/ISG15 deconjugase activity), but in P. berghei its Atg8-deconjugation function is redundant with Atg4 (the two are synthetically lethal when both deleted), and Otu irreversibly inactivates Atg8 by cleaving N-terminal to glycine rather than releasing it for recycling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1141700 (PfOTU) is an OTU-domain cysteine protease that localizes to vesicular compartments and associates with the apicoplast in P. falciparum, where it is essential for apicoplast homeostasis [#0, #1]. Conditional depletion causes abnormal apicoplast development, arrests parasites beyond the early-schizont stage, and impairs apicoplast protein import, phenotypes consistent with a role in the trafficking machinery that supplies the organelle [#1]. Its mechanistic activity centers on Atg8: PfOTU is implicated in deconjugating membrane-bound Atg8 (Atg8-PE cleavage) [#2], and across Plasmodium species the enzyme also displays ubiquitin/ISG15 deconjugase activity attributed to its OTU catalytic residues [#6]. Species comparison refines this picture: the P. berghei ortholog is individually dispensable at blood, mosquito, and liver stages but is synthetically lethal with Atg4, showing that the two enzymes share a redundant Atg8-deconjugation function; unlike Atg4, Otu cleaves N-terminal to the Atg8 glycine, irreversibly inactivating Atg8 rather than releasing it for recycling [#3, #4, #5]. Beyond the apicoplast/Atg8 axis and its deconjugase chemistry, no further mechanistic detail for this gene has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing where PfOTU acts and whether it matters answered whether this OTU-domain protein has an organelle-specific role, placing it at the apicoplast as an essential factor for organelle biogenesis and protein import.\",\n      \"evidence\": \"Endogenous C-terminal fluorescent tagging with live imaging and fractionation, plus degradation-tag conditional knockdown with apicoplast morphology, protein-import, and isoprenoid-rescue readouts, in P. falciparum\",\n      \"pmids\": [\"28423214\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular substrate directly linking PfOTU protease activity to protein import not identified in vitro\",\n        \"Mechanism by which loss of PfOTU blocks import versus organelle maintenance not separated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connecting PfOTU to Atg8 membrane deconjugation proposed the biochemical activity underlying its apicoplast function, linking a cysteine protease to Atg8-PE cleavage.\",\n      \"evidence\": \"Knockdown combined with Atg8 membrane association assay (indirect functional inference) in P. falciparum\",\n      \"pmids\": [\"28423214\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Deconjugation inferred from knockdown phenotype rather than direct in vitro reconstitution\",\n        \"Cleavage specificity and catalytic residues not directly demonstrated in this work\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrating deconjugase chemistry addressed whether the OTU domain is catalytically active, showing ubiquitin and ISG15 deconjugation activity for Plasmodium OTU.\",\n      \"evidence\": \"Cellular deconjugation assay with western blot and flow cytometry for intracellular ubiquitinated proteins plus computational modeling of catalytic residues, in P. falciparum, P. vivax, and P. yoelii\",\n      \"pmids\": [\"34486667\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Activity measured by indirect intracellular ubiquitin content rather than direct in vitro reconstitution with purified enzyme\",\n        \"Structural placement of catalytic residues is computational, not experimentally solved\",\n        \"Relationship between ubiquitin/ISG15 activity and the apicoplast Atg8 role unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium vivax\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Genetic dissection in P. berghei answered whether Otu is individually essential and how its Atg8 activity relates to Atg4, revealing redundancy via synthetic lethality and a mechanistically distinct, irreversible mode of Atg8 processing.\",\n      \"evidence\": \"Knockout with multi-stage phenotyping, refractory double-KO (synthetic lethality) with Atg4, and in vitro determination of the Atg8 cleavage site, in P. berghei\",\n      \"pmids\": [\"37910326\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Species divergence: P. berghei Otu is individually dispensable whereas P. falciparum knockdown is lethal for apicoplast development\",\n        \"Why irreversible N-terminal-to-glycine cleavage cannot substitute for Atg4 recycling in vivo not fully resolved\",\n        \"Direct biochemical link between synthetic-lethal Atg8 function and apicoplast import not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PfOTU's ubiquitin/ISG15 deconjugase activity and its Atg8-deconjugation activity operate on the same or distinct pathways, and which activity underlies the apicoplast protein-import defect, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct in vitro reconstitution of PF3D7_1141700 protease on a defined apicoplast substrate\",\n        \"No structure of the P. falciparum enzyme\",\n        \"The mechanistic reason species differ in individual essentiality is unknown\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004843\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0008234\", \"supporting_discovery_ids\": [0, 2, 5]},\n      {\"term_id\": \"GO:0019783\", \"supporting_discovery_ids\": [2, 5, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009507\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006508\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0045037\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016237\", \"supporting_discovery_ids\": [2, 4, 5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Atg8 (deconjugation substrate) [#2, #5]\",\n      \"Atg4 (synthetically lethal / functionally redundant) [#4]\"\n    ],\n    \"other_free_text\": [\n      \"PfOTU (PF3D7_1141700) is essential for apicoplast development, protein import, and progression beyond the early-schizont stage in P. falciparum [#1].\",\n      \"The P. berghei ortholog is individually dispensable across blood, mosquito, and liver stages but essential in combination with Atg4 [#3, #4].\",\n      \"Otu cleaves Atg8 N-terminal to the glycine residue, irreversibly inactivating it rather than enabling recycling, distinguishing it mechanistically from Atg4 [#5].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1141700","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_1019900, PF3D7_1031400, PF3D7_1417300). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1141700","name":null,"product":"OTU domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0907300","name":null,"product":"OTU domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0939500","name":null,"product":"OTU domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}