{"gene":"PF3D7_1031400","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2017,"finding":"PfOTU (PF3D7_1031400) localizes to vesicular structures and associates with the apicoplast in P. falciparum, as determined by C-terminal regulatable fluorescent affinity tagging of the native protein.","method":"C-terminal regulatable fluorescent affinity tag (live imaging/localization)","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence, single lab, multiple functional assays","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Knockdown of PfOTU (PF3D7_1031400) using a degradation-tag system results in abnormal apicoplast development, blocks parasite development beyond early-schizont stage, and impairs apicoplast protein import, establishing PfOTU as essential for apicoplast homeostasis.","method":"Degradation-tag mediated knockdown with apicoplast morphology assay, protein import assay, and isoprenoid precursor rescue experiment","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean knockdown with multiple orthogonal functional readouts (morphology, protein import, metabolic rescue) in a single rigorous study","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PfOTU (PF3D7_1031400) is implicated in membrane deconjugation (delipidation) of Atg8, suggesting it functions as a deubiquitylase/deconjugase that cleaves Atg8 from phosphatidylethanolamine on autophagosomal/apicoplast membranes.","method":"Functional characterization via knockdown and association studies with Atg8","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, indirect evidence for Atg8 deconjugation activity without direct in vitro cleavage assay reported in abstract","pmids":["28423214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In P. berghei, Otu (ortholog of PF3D7_1031400) localizes to the apicoplast; individual gene knockout of Otu is viable with no visible blood or mosquito stage developmental defects, but simultaneous deletion of Otu and Atg4 is refractory and essential for parasite survival, indicating functional redundancy in Atg8 deconjugation.","method":"Gene knockout (individual and simultaneous), in vivo mouse infection assays, in vitro developmental analysis, fluorescence localization","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal KO genetics with in vivo and in vitro validation, confirmed by multiple developmental assays across labs","pmids":["37910326"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"Otu (ortholog of PF3D7_1031400) cleaves the peptide bond on the N-terminal side of glycine on Atg8, thereby irreversibly inactivating Atg8 and preventing its recycling, which distinguishes its mechanism from Atg4 and explains why Otu cannot fully substitute for Atg4 function.","method":"In vitro deconjugation assay, western blot quantification of Atg8 levels in KO parasites, genetic complementation analysis","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic cleavage site determination supported by in vitro and in vivo data, single lab","pmids":["37910326"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"finding":"PfOTU (PF3D7_1031400) and its orthologs in P. vivax and P. yoelii exhibit ubiquitin and ISG15 deconjugation activities, as demonstrated by intracellular ubiquitinated protein content assays and in vitro deconjugation assays, with catalytic and inhibition pockets conserved with viral OTU proteins.","method":"Deconjugation assays, western blot and flow cytometry of ubiquitinated protein content, structural modeling, enzyme kinetics","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzymatic activity demonstrated with multiple methods (deconjugation assay, western blot, flow cytometry), single lab","pmids":["34486667"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium vivax","strain":""},{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"PF3D7_1031400 (OTU) is an OTU-domain cysteine protease that localizes to the apicoplast in Plasmodium, where it is essential for apicoplast homeostasis and protein import in P. falciparum; it deconjugates Atg8 from phosphatidylethanolamine membranes (and cleaves ubiquitin/ISG15 conjugates) but does so by cutting on the N-terminal side of the terminal glycine, irreversibly inactivating Atg8 rather than recycling it, making Otu/OTU functionally redundant with but mechanistically distinct from Atg4 in Atg8 membrane deconjugation."},"narrative":{"mechanistic_narrative":"PF3D7_1031400 (OTU) is an OTU-domain cysteine protease that localizes to vesicular structures associated with the apicoplast and is essential for apicoplast homeostasis in P. falciparum [PMID:28423214]. Knockdown produces abnormal apicoplast development, arrests parasites beyond the early-schizont stage, and impairs apicoplast protein import [PMID:28423214]. Mechanistically, OTU acts as a deconjugase: in P. falciparum (and its P. vivax and P. yoelii orthologs) it cleaves ubiquitin and ISG15 conjugates in vitro, with catalytic and inhibition pockets conserved with viral OTU proteins [PMID:34486667], and it deconjugates Atg8 from phosphatidylethanolamine membranes [PMID:28423214]. In P. berghei, the ortholog similarly localizes to the apicoplast and is individually dispensable but genetically redundant with Atg4, since simultaneous deletion of both is lethal [PMID:37910326]; however, OTU cleaves Atg8 on the N-terminal side of its terminal glycine, irreversibly inactivating Atg8 rather than recycling it, which mechanistically distinguishes it from Atg4 [PMID:37910326]. Beyond these apicoplast and deconjugation roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing where the protein acts and whether it is required addressed whether this OTU protease has an organelle-specific role in the parasite.","evidence":"C-terminal regulatable fluorescent affinity tagging with live imaging, plus degradation-tag knockdown coupled to apicoplast morphology, protein import, and isoprenoid rescue assays in P. falciparum","pmids":["28423214"],"confidence":"High","gaps":["Direct catalytic contribution to apicoplast function not separated from a structural role","The molecular target whose processing drives apicoplast protein import was not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Linking OTU to Atg8 delipidation proposed a substrate connecting the protease to autophagy/apicoplast membrane dynamics.","evidence":"Knockdown and association studies with Atg8 in P. falciparum","pmids":["28423214"],"confidence":"Medium","gaps":["No direct in vitro Atg8 cleavage assay reported in this study","Cleavage site and mechanism not resolved at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Demonstrating enzymatic deconjugation activity established OTU as a functional deubiquitylase/deISGylase rather than an inferred one.","evidence":"In vitro deconjugation assays, western blot and flow cytometry of ubiquitinated protein content, structural modeling, and enzyme kinetics for P. falciparum, P. vivax, and P. yoelii orthologs","pmids":["34486667"],"confidence":"Medium","gaps":["In-cell ubiquitin/ISG15 substrates in the parasite not defined","Relationship between deubiquitylase activity and the apicoplast phenotype not established","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium vivax","strain":""},{"species":"Plasmodium yoelii","strain":""}]},{"year":2023,"claim":"Reciprocal genetics resolved why the individually dispensable protease is nonetheless important, revealing functional redundancy with Atg4 in Atg8 deconjugation.","evidence":"Individual and simultaneous gene knockout, in vivo mouse infection and in vitro developmental analysis, and fluorescence localization in P. berghei","pmids":["37910326"],"confidence":"High","gaps":["P. berghei dispensability contrasts with essentiality reported for the P. falciparum ortholog; the basis of this species difference is unresolved","The shared essential process compensated by Atg4 was not molecularly dissected"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Mapping the cleavage site explained why OTU cannot fully replace Atg4 despite acting on the same substrate.","evidence":"In vitro deconjugation assay, western blot quantification of Atg8 in knockout parasites, and genetic complementation in P. berghei","pmids":["37910326"],"confidence":"Medium","gaps":["Structural basis for cleavage on the N-terminal side of the terminal glycine not determined","Physiological consequence of irreversible Atg8 inactivation versus recycling not quantified in vivo","Single lab"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"It remains unknown how OTU's deubiquitylase/deISGylase activity and its irreversible Atg8-inactivating activity are coordinated and which physiological substrates drive the apicoplast import phenotype.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in-cell substrate roster linking deconjugation activity to apicoplast biogenesis","No structural model of the catalytic mechanism for this specific protein","Species-divergent essentiality (P. falciparum vs P. berghei) unexplained"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ATG8 (SUBSTRATE)","ATG4 (FUNCTIONALLY REDUNDANT IN ATG8 DECONJUGATION, P. BERGHEI)"],"other_free_text":["OTU-domain cysteine protease with catalytic and inhibition pockets conserved with viral OTU proteins [#5]","Cleaves Atg8 on the N-terminal side of the terminal glycine, irreversibly inactivating it rather than recycling it [#4]","Essential for apicoplast homeostasis and protein import in P. falciparum [#1]; individually dispensable in P. berghei but lethal when co-deleted with Atg4 [#3]"]}},"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":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OTU","OTU-like cysteine protease","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":12,"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":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OTU"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42473197","id":"PMC_42473197","title":"Divergent Autophagy Pathways in Plasmodium: Mechanisms, Functions, and Therapeutic Potential.","date":"2026","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42473197","citation_count":0,"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":4916,"output_tokens":1721,"usd":0.020282,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6758,"output_tokens":2671,"usd":0.050283,"stage2_stop_reason":"end_turn"},"total_usd":0.070565,"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_1031400) localizes to vesicular structures and associates with the apicoplast in P. falciparum, as determined by C-terminal regulatable fluorescent affinity tagging of the native protein.\",\n      \"method\": \"C-terminal regulatable fluorescent affinity tag (live imaging/localization)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence, single lab, multiple functional assays\",\n      \"pmids\": [\"28423214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Knockdown of PfOTU (PF3D7_1031400) using a degradation-tag system results in abnormal apicoplast development, blocks parasite development beyond early-schizont stage, and impairs apicoplast protein import, establishing PfOTU as essential for apicoplast homeostasis.\",\n      \"method\": \"Degradation-tag mediated knockdown with apicoplast morphology assay, protein import assay, and isoprenoid precursor rescue experiment\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with multiple orthogonal functional readouts (morphology, protein import, metabolic 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_1031400) is implicated in membrane deconjugation (delipidation) of Atg8, suggesting it functions as a deubiquitylase/deconjugase that cleaves Atg8 from phosphatidylethanolamine on autophagosomal/apicoplast membranes.\",\n      \"method\": \"Functional characterization via knockdown and association studies with Atg8\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect evidence for Atg8 deconjugation activity without direct in vitro cleavage assay reported in abstract\",\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_1031400) localizes to the apicoplast; individual gene knockout of Otu is viable with no visible blood or mosquito stage developmental defects, but simultaneous deletion of Otu and Atg4 is refractory and essential for parasite survival, indicating functional redundancy in Atg8 deconjugation.\",\n      \"method\": \"Gene knockout (individual and simultaneous), in vivo mouse infection assays, in vitro developmental analysis, fluorescence localization\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal KO genetics with in vivo and in vitro validation, confirmed by multiple developmental assays across labs\",\n      \"pmids\": [\"37910326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Otu (ortholog of PF3D7_1031400) cleaves the peptide bond on the N-terminal side of glycine on Atg8, thereby irreversibly inactivating Atg8 and preventing its recycling, which distinguishes its mechanism from Atg4 and explains why Otu cannot fully substitute for Atg4 function.\",\n      \"method\": \"In vitro deconjugation assay, western blot quantification of Atg8 levels in KO parasites, genetic complementation analysis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic cleavage site determination supported by in vitro and in vivo data, single lab\",\n      \"pmids\": [\"37910326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfOTU (PF3D7_1031400) and its orthologs in P. vivax and P. yoelii exhibit ubiquitin and ISG15 deconjugation activities, as demonstrated by intracellular ubiquitinated protein content assays and in vitro deconjugation assays, with catalytic and inhibition pockets conserved with viral OTU proteins.\",\n      \"method\": \"Deconjugation assays, western blot and flow cytometry of ubiquitinated protein content, structural modeling, enzyme kinetics\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzymatic activity demonstrated with multiple methods (deconjugation assay, western blot, flow cytometry), single lab\",\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_1031400 (OTU) is an OTU-domain cysteine protease that localizes to the apicoplast in Plasmodium, where it is essential for apicoplast homeostasis and protein import in P. falciparum; it deconjugates Atg8 from phosphatidylethanolamine membranes (and cleaves ubiquitin/ISG15 conjugates) but does so by cutting on the N-terminal side of the terminal glycine, irreversibly inactivating Atg8 rather than recycling it, making Otu/OTU functionally redundant with but mechanistically distinct from Atg4 in Atg8 membrane deconjugation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1031400 (OTU) is an OTU-domain cysteine protease that localizes to vesicular structures associated with the apicoplast and is essential for apicoplast homeostasis in P. falciparum [#0, #1]. Knockdown produces abnormal apicoplast development, arrests parasites beyond the early-schizont stage, and impairs apicoplast protein import [#1]. Mechanistically, OTU acts as a deconjugase: in P. falciparum (and its P. vivax and P. yoelii orthologs) it cleaves ubiquitin and ISG15 conjugates in vitro, with catalytic and inhibition pockets conserved with viral OTU proteins [#5], and it deconjugates Atg8 from phosphatidylethanolamine membranes [#2]. In P. berghei, the ortholog similarly localizes to the apicoplast and is individually dispensable but genetically redundant with Atg4, since simultaneous deletion of both is lethal [#3]; however, OTU cleaves Atg8 on the N-terminal side of its terminal glycine, irreversibly inactivating Atg8 rather than recycling it, which mechanistically distinguishes it from Atg4 [#4]. Beyond these apicoplast and deconjugation roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing where the protein acts and whether it is required addressed whether this OTU protease has an organelle-specific role in the parasite.\",\n      \"evidence\": \"C-terminal regulatable fluorescent affinity tagging with live imaging, plus degradation-tag knockdown coupled to apicoplast morphology, protein import, and isoprenoid rescue assays in P. falciparum\",\n      \"pmids\": [\"28423214\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct catalytic contribution to apicoplast function not separated from a structural role\",\n        \"The molecular target whose processing drives apicoplast protein import was not identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Linking OTU to Atg8 delipidation proposed a substrate connecting the protease to autophagy/apicoplast membrane dynamics.\",\n      \"evidence\": \"Knockdown and association studies with Atg8 in P. falciparum\",\n      \"pmids\": [\"28423214\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct in vitro Atg8 cleavage assay reported in this study\",\n        \"Cleavage site and mechanism not resolved at this stage\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrating enzymatic deconjugation activity established OTU as a functional deubiquitylase/deISGylase rather than an inferred one.\",\n      \"evidence\": \"In vitro deconjugation assays, western blot and flow cytometry of ubiquitinated protein content, structural modeling, and enzyme kinetics for P. falciparum, P. vivax, and P. yoelii orthologs\",\n      \"pmids\": [\"34486667\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"In-cell ubiquitin/ISG15 substrates in the parasite not defined\",\n        \"Relationship between deubiquitylase activity and the apicoplast phenotype not established\",\n        \"Single lab\"\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\": \"Reciprocal genetics resolved why the individually dispensable protease is nonetheless important, revealing functional redundancy with Atg4 in Atg8 deconjugation.\",\n      \"evidence\": \"Individual and simultaneous gene knockout, in vivo mouse infection and in vitro developmental analysis, and fluorescence localization in P. berghei\",\n      \"pmids\": [\"37910326\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"P. berghei dispensability contrasts with essentiality reported for the P. falciparum ortholog; the basis of this species difference is unresolved\",\n        \"The shared essential process compensated by Atg4 was not molecularly dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapping the cleavage site explained why OTU cannot fully replace Atg4 despite acting on the same substrate.\",\n      \"evidence\": \"In vitro deconjugation assay, western blot quantification of Atg8 in knockout parasites, and genetic complementation in P. berghei\",\n      \"pmids\": [\"37910326\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis for cleavage on the N-terminal side of the terminal glycine not determined\",\n        \"Physiological consequence of irreversible Atg8 inactivation versus recycling not quantified in vivo\",\n        \"Single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how OTU's deubiquitylase/deISGylase activity and its irreversible Atg8-inactivating activity are coordinated and which physiological substrates drive the apicoplast import phenotype.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in-cell substrate roster linking deconjugation activity to apicoplast biogenesis\",\n        \"No structural model of the catalytic mechanism for this specific protein\",\n        \"Species-divergent essentiality (P. falciparum vs P. berghei) unexplained\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004843\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0019784\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0019786\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0008234\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009507\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006914\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0045037\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Atg8 (substrate)\",\n      \"Atg4 (functionally redundant in Atg8 deconjugation, P. berghei)\"\n    ],\n    \"other_free_text\": [\n      \"OTU-domain cysteine protease with catalytic and inhibition pockets conserved with viral OTU proteins [#5]\",\n      \"Cleaves Atg8 on the N-terminal side of the terminal glycine, irreversibly inactivating it rather than recycling it [#4]\",\n      \"Essential for apicoplast homeostasis and protein import in P. falciparum [#1]; individually dispensable in P. berghei but lethal when co-deleted with Atg4 [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1031400","name":null,"product":"OTU-like cysteine protease","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0515350","name":null,"product":"OTU-like cysteine protease, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0616100","name":null,"product":"OTU-like cysteine protease, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"OTU","evaluation":null}