{"gene":"PF3D7_0826100","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2025,"finding":"PF3D7_0826100 (PfHEUL) was captured by a ubiquitin activity-based probe (Ub-Dha) and validated as an active HECT E3 ubiquitin ligase through in vitro ubiquitination assays. PfHEUL shows selective functional interactions with a subset of both human and P. falciparum E2 ubiquitin-conjugating enzymes.","method":"Activity-based protein profiling with ubiquitin-Dha probe, in vitro ubiquitination assay, biochemical interaction analysis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro ubiquitination assay directly validates enzymatic activity; E2 selectivity established biochemically in a single rigorous study with multiple orthogonal methods","pmids":["40249735"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_0826100 (referred to as a HECT E3 protein-ubiquitin ligase) was identified as a functional target of PfPP1 (Protein Phosphatase 1) relevant to parasite egress from host red blood cells, via phosphoproteomic and chemical-genetic analysis.","method":"Phosphoproteomics, chemical-genetic analysis","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (phosphoproteomics + chemical-genetic) identify PF3D7_0826100 as a PfPP1 substrate/target in a single study, but functional validation of the specific PF3D7_0826100-PfPP1 interaction is not elaborated beyond identification","pmids":["32669539"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Overexpression of PF3D7_0826100 (PfUT) — achieved by insertion of the glmS ribozyme in the 3′ UTR which unexpectedly increased RNA and protein ~2.5-fold — resulted in S/M phase-associated lengthening of the intraerythrocytic developmental cycle and reduced merozoite invasion efficiency; partial restoration of wild-type phenotype by glucosamine confirmed the role of expression level in these phenotypes.","method":"Conditional expression system (glmS ribozyme), parasite cell cycle staging, invasion efficiency assay","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined cellular phenotypes (cell cycle prolongation, reduced invasion) linked to overexpression of the specific gene with glucosamine rescue control, single lab, no direct mechanistic dissection of catalytic mechanism","pmids":["31797898"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Episomal overexpression of PF3D7_0826100 (MAL7P1.19, encoding a HECT ubiquitin ligase) in P. falciparum altered quinine and quinidine sensitivity (~2-fold change in IC50) in a subset of genetic backgrounds, establishing a direct functional role for this ligase in drug response, although the effect was background-dependent and moderate.","method":"Episomal transfection, drug IC50 assay, quantitative trait locus analysis, genetic cross","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — episomal transfection with functional drug-response readout, but effect was moderate and background-dependent; single lab","pmids":["24830312"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The P. yoelii ortholog of PF3D7_0826100 (Pyheul, a HECT-like E3 ubiquitin ligase) regulates parasite growth and host mortality; allelic exchange of partial Pyheul sequences between two lethal P. yoelii strains and modification of its expression level altered parasitemia and host survival, placing Pyheul in a QTL on chromosome 7 (LOD=8.1) linked to these phenotypes.","method":"Genetic cross, genome-wide QTL mapping, allelic exchange, gene expression modification","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — allelic exchange and expression modification provide direct genetic evidence; two orthogonal genetic approaches in a single study, attributed to the P. yoelii ortholog","pmids":["28790316"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"PF3D7_0826100 (PfHEUL) is an active HECT E3 ubiquitin ligase in P. falciparum that selectively interacts with a subset of E2 ubiquitin-conjugating enzymes, functions as a substrate/target of the phosphatase PfPP1 in the context of parasite egress from erythrocytes, and regulates intraerythrocytic cell cycle progression and merozoite invasion efficiency when overexpressed; its P. yoelii ortholog (Pyheul) similarly controls parasite growth and virulence via allelic variation."},"narrative":{"mechanistic_narrative":"PF3D7_0826100 (HEUL) is an active HECT E3 ubiquitin ligase in Plasmodium falciparum that participates in ubiquitin-dependent regulation of the intraerythrocytic developmental cycle [PMID:40249735, PMID:31797898]. Its enzymatic activity was established directly: HEUL is captured by a ubiquitin activity-based (Ub-Dha) probe and catalyzes ubiquitination in vitro, and it selectively engages a subset of both human and P. falciparum E2 ubiquitin-conjugating enzymes [PMID:40249735]. HEUL is a functional target of the phosphatase PfPP1 in the context of parasite egress from erythrocytes, linking its regulation to phospho-dependent control of the erythrocytic cycle [PMID:32669539]. Perturbing HEUL expression has cellular consequences: overexpression lengthens the S/M phase of the intraerythrocytic cycle and reduces merozoite invasion efficiency, and it modulates quinine/quinidine sensitivity in a genetic-background-dependent manner [PMID:31797898, PMID:24830312]. In P. yoelii, the ortholog Pyheul controls parasite growth and host mortality through allelic variation and expression level [PMID:28790316]. Beyond these findings, the physiological substrates of HEUL and the mechanistic basis of its PfPP1 regulation have not been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Before any biochemical characterization, it was unknown whether this HECT ligase had a functional role in the parasite; QTL-guided overexpression established a direct, if moderate, contribution to antimalarial drug response.","evidence":"Episomal overexpression with quinine/quinidine IC50 assays and QTL analysis across genetic backgrounds in P. falciparum","pmids":["24830312"],"confidence":"Medium","gaps":["Effect was background-dependent and modest","No mechanistic link between ubiquitin ligase activity and drug sensitivity established","No substrate identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"To test whether the ligase influences parasite fitness in vivo, the P. yoelii ortholog was mapped and manipulated, showing Pyheul regulates parasite growth and host mortality.","evidence":"Genetic cross, genome-wide QTL mapping (chromosome 7, LOD=8.1), allelic exchange and expression modification in P. yoelii","pmids":["28790316"],"confidence":"Medium","gaps":["Molecular mechanism connecting allelic variation to virulence unknown","Substrates of Pyheul not identified","Findings are on the ortholog, not P. falciparum HEUL directly"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2019,"claim":"It was unclear which cellular process HEUL affects; conditional overexpression pinned its dosage to S/M-phase cell-cycle progression and merozoite invasion efficiency.","evidence":"glmS-ribozyme conditional expression system (unexpectedly ~2.5-fold overexpression), cell-cycle staging, and invasion assays with glucosamine rescue in P. falciparum","pmids":["31797898"],"confidence":"Medium","gaps":["Phenotype from overexpression, not loss-of-function","Catalytic mechanism not dissected","Substrates driving the cell-cycle/invasion phenotype unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To place HEUL in a regulatory pathway, phosphoproteomic and chemical-genetic analysis identified it as a functional target of the phosphatase PfPP1 relevant to erythrocyte egress.","evidence":"Phosphoproteomics combined with chemical-genetic analysis of PfPP1 in P. falciparum","pmids":["32669539"],"confidence":"Medium","gaps":["Direct HEUL-PfPP1 interaction not validated beyond identification","Phosphosites and their functional consequences on ligase activity not defined","Role of dephosphorylation in egress not mechanistically resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether HEUL is a catalytically active ligase and which E2 enzymes it uses was unresolved; activity-based profiling confirmed active HECT ligase function and defined selective E2 usage.","evidence":"Ubiquitin-Dha activity-based probe capture, in vitro ubiquitination assay, and biochemical E2 interaction analysis in P. falciparum","pmids":["40249735"],"confidence":"High","gaps":["Physiological substrates not identified","Structural basis of E2 selectivity unknown","Link between in vitro activity and cell-cycle/egress phenotypes not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The endogenous substrates of HEUL and the mechanistic connection between its PfPP1-regulated phosphorylation, its ligase activity, and its roles in cell-cycle progression, egress, and invasion remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No ubiquitination substrate identified","No structural model of HEUL or its E2 complex","Loss-of-function/essentiality in P. falciparum not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPP1 (PROTEIN PHOSPHATASE 1) — REGULATORY RELATIONSHIP, HEUL IDENTIFIED AS FUNCTIONAL TARGET [#1]","E2 UBIQUITIN-CONJUGATING ENZYMES (SUBSET OF HUMAN AND P. FALCIPARUM E2S) — SELECTIVE FUNCTIONAL INTERACTION [#0]"],"other_free_text":["Active HECT E3 ubiquitin ligase validated by activity-based probe capture and in vitro ubiquitination [#0]","Overexpression lengthens S/M phase of the intraerythrocytic developmental cycle and reduces merozoite invasion efficiency [#2]","Episomal overexpression alters quinine/quinidine sensitivity in a genetic-background-dependent manner [#3]","P. yoelii ortholog Pyheul regulates parasite growth and host mortality via allelic variation and expression level (QTL on chromosome 7) [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32669539","id":"PMC_32669539","title":"Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32669539","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HECT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24830312","id":"PMC_24830312","title":"A HECT ubiquitin-protein ligase as a novel candidate gene for altered quinine and quinidine responses in Plasmodium falciparum.","date":"2014","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24830312","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HECT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28790316","id":"PMC_28790316","title":"A Plasmodium yoelii HECT-like E3 ubiquitin ligase regulates parasite growth and virulence.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28790316","citation_count":22,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HECT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31797898","id":"PMC_31797898","title":"Overexpression of the HECT ubiquitin ligase PfUT prolongs the intraerythrocytic cycle and reduces invasion efficiency of Plasmodium falciparum.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31797898","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HECT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40249735","id":"PMC_40249735","title":"Activity-based protein profiling reveals both canonical and novel ubiquitin pathway enzymes in Plasmodium.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/40249735","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HECT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5010,"output_tokens":1539,"usd":0.019058,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6565,"output_tokens":2673,"usd":0.049825,"stage2_stop_reason":"end_turn"},"total_usd":0.068883,"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\": 2025,\n      \"finding\": \"PF3D7_0826100 (PfHEUL) was captured by a ubiquitin activity-based probe (Ub-Dha) and validated as an active HECT E3 ubiquitin ligase through in vitro ubiquitination assays. PfHEUL shows selective functional interactions with a subset of both human and P. falciparum E2 ubiquitin-conjugating enzymes.\",\n      \"method\": \"Activity-based protein profiling with ubiquitin-Dha probe, in vitro ubiquitination assay, biochemical interaction analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro ubiquitination assay directly validates enzymatic activity; E2 selectivity established biochemically in a single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"40249735\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_0826100 (referred to as a HECT E3 protein-ubiquitin ligase) was identified as a functional target of PfPP1 (Protein Phosphatase 1) relevant to parasite egress from host red blood cells, via phosphoproteomic and chemical-genetic analysis.\",\n      \"method\": \"Phosphoproteomics, chemical-genetic analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (phosphoproteomics + chemical-genetic) identify PF3D7_0826100 as a PfPP1 substrate/target in a single study, but functional validation of the specific PF3D7_0826100-PfPP1 interaction is not elaborated beyond identification\",\n      \"pmids\": [\"32669539\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Overexpression of PF3D7_0826100 (PfUT) — achieved by insertion of the glmS ribozyme in the 3′ UTR which unexpectedly increased RNA and protein ~2.5-fold — resulted in S/M phase-associated lengthening of the intraerythrocytic developmental cycle and reduced merozoite invasion efficiency; partial restoration of wild-type phenotype by glucosamine confirmed the role of expression level in these phenotypes.\",\n      \"method\": \"Conditional expression system (glmS ribozyme), parasite cell cycle staging, invasion efficiency assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined cellular phenotypes (cell cycle prolongation, reduced invasion) linked to overexpression of the specific gene with glucosamine rescue control, single lab, no direct mechanistic dissection of catalytic mechanism\",\n      \"pmids\": [\"31797898\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Episomal overexpression of PF3D7_0826100 (MAL7P1.19, encoding a HECT ubiquitin ligase) in P. falciparum altered quinine and quinidine sensitivity (~2-fold change in IC50) in a subset of genetic backgrounds, establishing a direct functional role for this ligase in drug response, although the effect was background-dependent and moderate.\",\n      \"method\": \"Episomal transfection, drug IC50 assay, quantitative trait locus analysis, genetic cross\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — episomal transfection with functional drug-response readout, but effect was moderate and background-dependent; single lab\",\n      \"pmids\": [\"24830312\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The P. yoelii ortholog of PF3D7_0826100 (Pyheul, a HECT-like E3 ubiquitin ligase) regulates parasite growth and host mortality; allelic exchange of partial Pyheul sequences between two lethal P. yoelii strains and modification of its expression level altered parasitemia and host survival, placing Pyheul in a QTL on chromosome 7 (LOD=8.1) linked to these phenotypes.\",\n      \"method\": \"Genetic cross, genome-wide QTL mapping, allelic exchange, gene expression modification\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — allelic exchange and expression modification provide direct genetic evidence; two orthogonal genetic approaches in a single study, attributed to the P. yoelii ortholog\",\n      \"pmids\": [\"28790316\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0826100 (PfHEUL) is an active HECT E3 ubiquitin ligase in P. falciparum that selectively interacts with a subset of E2 ubiquitin-conjugating enzymes, functions as a substrate/target of the phosphatase PfPP1 in the context of parasite egress from erythrocytes, and regulates intraerythrocytic cell cycle progression and merozoite invasion efficiency when overexpressed; its P. yoelii ortholog (Pyheul) similarly controls parasite growth and virulence via allelic variation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0826100 (HEUL) is an active HECT E3 ubiquitin ligase in Plasmodium falciparum that participates in ubiquitin-dependent regulation of the intraerythrocytic developmental cycle [#0, #2]. Its enzymatic activity was established directly: HEUL is captured by a ubiquitin activity-based (Ub-Dha) probe and catalyzes ubiquitination in vitro, and it selectively engages a subset of both human and P. falciparum E2 ubiquitin-conjugating enzymes [#0]. HEUL is a functional target of the phosphatase PfPP1 in the context of parasite egress from erythrocytes, linking its regulation to phospho-dependent control of the erythrocytic cycle [#1]. Perturbing HEUL expression has cellular consequences: overexpression lengthens the S/M phase of the intraerythrocytic cycle and reduces merozoite invasion efficiency, and it modulates quinine/quinidine sensitivity in a genetic-background-dependent manner [#2, #3]. In P. yoelii, the ortholog Pyheul controls parasite growth and host mortality through allelic variation and expression level [#4]. Beyond these findings, the physiological substrates of HEUL and the mechanistic basis of its PfPP1 regulation have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Before any biochemical characterization, it was unknown whether this HECT ligase had a functional role in the parasite; QTL-guided overexpression established a direct, if moderate, contribution to antimalarial drug response.\",\n      \"evidence\": \"Episomal overexpression with quinine/quinidine IC50 assays and QTL analysis across genetic backgrounds in P. falciparum\",\n      \"pmids\": [\"24830312\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effect was background-dependent and modest\", \"No mechanistic link between ubiquitin ligase activity and drug sensitivity established\", \"No substrate identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To test whether the ligase influences parasite fitness in vivo, the P. yoelii ortholog was mapped and manipulated, showing Pyheul regulates parasite growth and host mortality.\",\n      \"evidence\": \"Genetic cross, genome-wide QTL mapping (chromosome 7, LOD=8.1), allelic exchange and expression modification in P. yoelii\",\n      \"pmids\": [\"28790316\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism connecting allelic variation to virulence unknown\", \"Substrates of Pyheul not identified\", \"Findings are on the ortholog, not P. falciparum HEUL directly\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"It was unclear which cellular process HEUL affects; conditional overexpression pinned its dosage to S/M-phase cell-cycle progression and merozoite invasion efficiency.\",\n      \"evidence\": \"glmS-ribozyme conditional expression system (unexpectedly ~2.5-fold overexpression), cell-cycle staging, and invasion assays with glucosamine rescue in P. falciparum\",\n      \"pmids\": [\"31797898\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phenotype from overexpression, not loss-of-function\", \"Catalytic mechanism not dissected\", \"Substrates driving the cell-cycle/invasion phenotype unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To place HEUL in a regulatory pathway, phosphoproteomic and chemical-genetic analysis identified it as a functional target of the phosphatase PfPP1 relevant to erythrocyte egress.\",\n      \"evidence\": \"Phosphoproteomics combined with chemical-genetic analysis of PfPP1 in P. falciparum\",\n      \"pmids\": [\"32669539\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct HEUL-PfPP1 interaction not validated beyond identification\", \"Phosphosites and their functional consequences on ligase activity not defined\", \"Role of dephosphorylation in egress not mechanistically resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether HEUL is a catalytically active ligase and which E2 enzymes it uses was unresolved; activity-based profiling confirmed active HECT ligase function and defined selective E2 usage.\",\n      \"evidence\": \"Ubiquitin-Dha activity-based probe capture, in vitro ubiquitination assay, and biochemical E2 interaction analysis in P. falciparum\",\n      \"pmids\": [\"40249735\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological substrates not identified\", \"Structural basis of E2 selectivity unknown\", \"Link between in vitro activity and cell-cycle/egress phenotypes not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous substrates of HEUL and the mechanistic connection between its PfPP1-regulated phosphorylation, its ligase activity, and its roles in cell-cycle progression, egress, and invasion remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No ubiquitination substrate identified\", \"No structural model of HEUL or its E2 complex\", \"Loss-of-function/essentiality in P. falciparum not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061630\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0031624\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016567\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0051701\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfPP1 (Protein Phosphatase 1) — regulatory relationship, HEUL identified as functional target [#1]\",\n      \"E2 ubiquitin-conjugating enzymes (subset of human and P. falciparum E2s) — selective functional interaction [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Active HECT E3 ubiquitin ligase validated by activity-based probe capture and in vitro ubiquitination [#0]\",\n      \"Overexpression lengthens S/M phase of the intraerythrocytic developmental cycle and reduces merozoite invasion efficiency [#2]\",\n      \"Episomal overexpression alters quinine/quinidine sensitivity in a genetic-background-dependent manner [#3]\",\n      \"P. yoelii ortholog Pyheul regulates parasite growth and host mortality via allelic variation and expression level (QTL on chromosome 7) [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0826100","name":null,"product":"HECT-like E3 ubiquitin ligase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0704500","name":null,"product":"HECT-like E3 ubiquitin ligase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1320300","name":null,"product":"HECT-like E3 ubiquitin ligase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"HEUL","evaluation":null}