{"gene":"PF3D7_1233900","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2011,"finding":"The catalytic domain of SENP1 (PfSENP1, PFL1635w) was expressed recombinantly and shown by biochemical profiling with a positional scanning substrate library to have a unique cleavage sequence preference relative to human SENPs, demonstrating it is a functional SUMO-specific protease with distinct substrate specificity.","method":"Recombinant protein expression, positional scanning substrate library profiling (in vitro enzymatic assay)","journal":"Chemistry & biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with positional scanning library, recombinant catalytic domain, single lab but multiple orthogonal biochemical methods","pmids":["21700207"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"SENP1 cleaves human SUMO-1 from the lysine motifs of modified RanGAP1 and processes SUMO precursors in vitro, establishing its deconjugase and maturation activities.","method":"In vitro deSUMOylation assay using recombinant SENP1 catalytic domain with SUMO-RanGAP1 substrate and SUMO precursor substrates","journal":"Chemistry & biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstituted enzymatic assay with defined substrates, single lab, multiple substrate types tested","pmids":["21700207"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"A class of aza-epoxide small molecule inhibitors of SENP1 (most potent: VEA-260) blocked both recombinant SENP1 enzymatic activity and P. falciparum replication in infected human erythrocytes, with parasite clearance correlating directly with potency of SENP1 inhibition; the most potent inhibitor also altered late schizont morphology and disabled parasite egress from the red blood cell.","method":"Small molecule inhibitor screen, in vitro protease inhibition assay, P. falciparum erythrocyte culture replication assay, morphological analysis of infected RBCs","journal":"Chemistry & biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pharmacological (not genetic) target validation, multiple orthogonal assays in single lab; egress phenotype is pharmacological only","pmids":["21700207"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"SENP1 was successfully expressed as a recombinant protein in E. coli using a CPD-His6 fusion tag system, and purified to near-homogeneity sufficient to obtain diffraction-quality crystals, establishing feasibility of structural studies.","method":"Recombinant protein expression in E. coli, affinity chromatography, gel filtration chromatography, crystal growth","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — methodological paper demonstrating purification; crystallization result is unpublished/preliminary and no structure was reported","pmids":["19956581"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"SENP1 was identified by proximity labeling (TurboID) of the P. berghei nuclear pore complex scaffold protein Nup313, placing SENP1 in physical proximity to the nuclear pore complex.","method":"TurboID proximity labeling followed by affinity purification and mass spectrometry","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling detects proteins in the vicinity of the bait but does not confirm direct interaction; single study, single method","pmids":["36040030"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"SENP1 transcript was upregulated ~5.4-fold in intrahepatic P. falciparum sporozoites on day 3 post-infection following γ-irradiation attenuation, as measured by genome-wide microarray, suggesting a role for SENP1 in the stress/radiation response during liver-stage development.","method":"Genome-wide transcriptional profiling by microarray of liver-stage parasites","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Weak — transcriptomic/expression data only, no direct mechanistic experiment on SENP1 itself","pmids":["27911910"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SENP1 (PF3D7_1233900) is a catalytically active SUMO-specific cysteine protease whose recombinant catalytic domain cleaves SUMO from modified substrates (e.g., RanGAP1) and processes SUMO precursors in vitro; it displays a substrate cleavage preference distinct from human SENPs, and its pharmacological inhibition blocks intraerythrocytic parasite replication and prevents schizont egress from red blood cells, while proximity-labeling data place it in the vicinity of the nuclear pore complex in P. berghei."},"narrative":{"mechanistic_narrative":"SENP1 (PF3D7_1233900) is a catalytically active SUMO-specific cysteine protease of P. falciparum that operates in the parasite's SUMOylation cycle [PMID:21700207]. Biochemical profiling of the recombinant catalytic domain with a positional scanning substrate library established it as a functional SUMO protease whose cleavage-sequence preference is distinct from that of human SENPs [PMID:21700207]. In reconstituted in vitro assays, SENP1 performs both arms of SUMO metabolism: it deconjugates SUMO-1 from modified RanGAP1 (isopeptidase/deSUMOylase activity) and processes SUMO precursors to their mature form (maturation activity) [PMID:21700207]. Its enzymatic activity is required for the intraerythrocytic cycle: aza-epoxide small-molecule inhibitors (most potent VEA-260) block recombinant SENP1 activity and P. falciparum replication in human erythrocytes, with parasite clearance tracking inhibitor potency, and the most potent compound disrupts late schizont morphology and prevents egress from the red blood cell [PMID:21700207]. In P. berghei, proximity labeling places SENP1 in the vicinity of the nuclear pore complex [PMID:36040030]. Beyond these findings, the direct substrates, structural basis, and genetic loss-of-function phenotype of SENP1 have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Before mechanistic work could proceed, it was unknown whether SENP1 could be produced as folded, homogeneous protein; establishing a purification route enabled all downstream biochemistry.","evidence":"Recombinant expression in E. coli via a CPD-His6 fusion tag, affinity and gel-filtration purification, and growth of diffraction-quality crystals","pmids":["19956581"],"confidence":"Low","gaps":["No crystal structure was reported despite diffraction-quality crystals","Purification demonstrates feasibility but establishes no catalytic or biological function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"It was unknown whether SENP1 is a genuine SUMO protease and how its specificity compares to human enzymes; profiling defined it as a functional SUMO-specific protease with a unique cleavage preference, marking it as biochemically distinct from human SENPs.","evidence":"Recombinant catalytic domain assayed with a positional scanning substrate library (in vitro)","pmids":["21700207"],"confidence":"High","gaps":["Distinct specificity does not identify the endogenous parasite substrates","Assay used a synthetic library rather than native Plasmodium SUMO conjugates"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"To confirm SENP1 carries out canonical SUMO-cycle chemistry, both its deconjugating and precursor-maturation activities were tested; it cleaved SUMO-1 from RanGAP1 and processed SUMO precursors, establishing dual deSUMOylase and maturation functions.","evidence":"In vitro deSUMOylation assay with recombinant catalytic domain against SUMO-RanGAP1 and SUMO precursor substrates","pmids":["21700207"],"confidence":"High","gaps":["Activities shown on human SUMO-1/RanGAP1 substrates, not native Plasmodium SUMO conjugates","Physiological substrates in the parasite remain unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Whether SENP1 activity matters for parasite viability was unresolved; pharmacological inhibition linked its enzymatic activity to intraerythrocytic replication and schizont egress, nominating it as a target for blood-stage growth and RBC exit.","evidence":"Aza-epoxide inhibitor screen (VEA-260) with in vitro protease inhibition, P. falciparum erythrocyte replication assays, and morphological analysis of infected RBCs","pmids":["21700207"],"confidence":"Medium","gaps":["Target validation is pharmacological only, not genetic; inhibitor off-target effects not excluded","Egress and morphology phenotypes are correlative to inhibition, not to defined SENP1 substrates","No genetic knockout/knockdown phenotype established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Whether SENP1 has roles outside blood stages was unexplored; transcriptional upregulation in attenuated liver-stage sporozoites raised a possible stress/radiation-response role, though at the expression level only.","evidence":"Genome-wide microarray of γ-irradiation-attenuated intrahepatic P. falciparum sporozoites (day 3 post-infection)","pmids":["27911910"],"confidence":"Low","gaps":["Transcript-only observation with no protein-level or functional follow-up on SENP1","Causal link between SENP1 and stress response not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"The subcellular context of SENP1 was undefined; proximity labeling of a nuclear pore scaffold placed it near the nuclear pore complex, hinting at a nuclear-envelope-associated context for its SUMO-processing activity.","evidence":"TurboID proximity labeling from P. berghei Nup313 followed by affinity purification and mass spectrometry","pmids":["36040030"],"confidence":"Low","gaps":["Proximity labeling does not establish direct interaction or stable localization","Shown in P. berghei, not confirmed for P. falciparum SENP1","Functional consequence of nuclear-pore proximity untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The endogenous SUMOylated substrates of SENP1, its genetic loss-of-function phenotype, and the structural basis of its distinct specificity remain unresolved in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No native Plasmodium substrate identified","No genetic knockout/knockdown phenotype","No experimental structure despite crystallization feasibility"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["NUP313 (P. BERGHEI NUCLEAR PORE COMPLEX SCAFFOLD; PROXIMITY-LABELING PROXIMITY ONLY) [#4]"],"other_free_text":["Recombinant catalytic domain cleaves human SUMO-1 from RanGAP1 in vitro; endogenous Plasmodium substrates unidentified [#1]","Cleavage-sequence preference distinct from human SENPs [#0]","Aza-epoxide inhibitor VEA-260 blocks enzymatic activity, parasite replication, schizont maturation, and RBC egress (pharmacological, not genetic, validation) [#2]","Transcript upregulated ~5.4-fold in γ-irradiation-attenuated liver-stage sporozoites (expression data only) [#5]","Purifiable as near-homogeneous recombinant protein yielding diffraction-quality crystals; no structure reported [#3]"]}},"prefetch_data":{},"corpus_meta":[{"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":["PFL1635w","PfSENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34178724","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36040030","id":"","title":"TurboID Identification of Evolutionarily Divergent Components of the Nuclear Pore Complex in the Malaria Model Plasmodium berghei.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36040030","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33022940","id":"","title":"Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites.","date":"2020","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/33022940","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28599096","id":"","title":"Proteases as antimalarial targets: strategies for genetic, chemical, and therapeutic validation.","date":"2017","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/28599096","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27911910","id":"","title":"Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27911910","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19956581","id":"","title":"Simplified, enhanced protein purification using an inducible, autoprocessing enzyme tag.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19956581","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SENP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9881,"output_tokens":1590,"usd":0.026746,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6607,"output_tokens":3020,"usd":0.054268,"stage2_stop_reason":"end_turn"},"total_usd":0.081014,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"The catalytic domain of SENP1 (PfSENP1, PFL1635w) was expressed recombinantly and shown by biochemical profiling with a positional scanning substrate library to have a unique cleavage sequence preference relative to human SENPs, demonstrating it is a functional SUMO-specific protease with distinct substrate specificity.\",\n      \"method\": \"Recombinant protein expression, positional scanning substrate library profiling (in vitro enzymatic assay)\",\n      \"journal\": \"Chemistry & biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with positional scanning library, recombinant catalytic domain, single lab but multiple orthogonal biochemical methods\",\n      \"pmids\": [\"21700207\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SENP1 cleaves human SUMO-1 from the lysine motifs of modified RanGAP1 and processes SUMO precursors in vitro, establishing its deconjugase and maturation activities.\",\n      \"method\": \"In vitro deSUMOylation assay using recombinant SENP1 catalytic domain with SUMO-RanGAP1 substrate and SUMO precursor substrates\",\n      \"journal\": \"Chemistry & biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstituted enzymatic assay with defined substrates, single lab, multiple substrate types tested\",\n      \"pmids\": [\"21700207\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"A class of aza-epoxide small molecule inhibitors of SENP1 (most potent: VEA-260) blocked both recombinant SENP1 enzymatic activity and P. falciparum replication in infected human erythrocytes, with parasite clearance correlating directly with potency of SENP1 inhibition; the most potent inhibitor also altered late schizont morphology and disabled parasite egress from the red blood cell.\",\n      \"method\": \"Small molecule inhibitor screen, in vitro protease inhibition assay, P. falciparum erythrocyte culture replication assay, morphological analysis of infected RBCs\",\n      \"journal\": \"Chemistry & biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological (not genetic) target validation, multiple orthogonal assays in single lab; egress phenotype is pharmacological only\",\n      \"pmids\": [\"21700207\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SENP1 was successfully expressed as a recombinant protein in E. coli using a CPD-His6 fusion tag system, and purified to near-homogeneity sufficient to obtain diffraction-quality crystals, establishing feasibility of structural studies.\",\n      \"method\": \"Recombinant protein expression in E. coli, affinity chromatography, gel filtration chromatography, crystal growth\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — methodological paper demonstrating purification; crystallization result is unpublished/preliminary and no structure was reported\",\n      \"pmids\": [\"19956581\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SENP1 was identified by proximity labeling (TurboID) of the P. berghei nuclear pore complex scaffold protein Nup313, placing SENP1 in physical proximity to the nuclear pore complex.\",\n      \"method\": \"TurboID proximity labeling followed by affinity purification and mass spectrometry\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling detects proteins in the vicinity of the bait but does not confirm direct interaction; single study, single method\",\n      \"pmids\": [\"36040030\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"SENP1 transcript was upregulated ~5.4-fold in intrahepatic P. falciparum sporozoites on day 3 post-infection following γ-irradiation attenuation, as measured by genome-wide microarray, suggesting a role for SENP1 in the stress/radiation response during liver-stage development.\",\n      \"method\": \"Genome-wide transcriptional profiling by microarray of liver-stage parasites\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — transcriptomic/expression data only, no direct mechanistic experiment on SENP1 itself\",\n      \"pmids\": [\"27911910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum SENP1 (PF3D7_1233900) is a catalytically active SUMO-specific cysteine protease whose recombinant catalytic domain cleaves SUMO from modified substrates (e.g., RanGAP1) and processes SUMO precursors in vitro; it displays a substrate cleavage preference distinct from human SENPs, and its pharmacological inhibition blocks intraerythrocytic parasite replication and prevents schizont egress from red blood cells, while proximity-labeling data place it in the vicinity of the nuclear pore complex in P. berghei.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SENP1 (PF3D7_1233900) is a catalytically active SUMO-specific cysteine protease of P. falciparum that operates in the parasite's SUMOylation cycle [#0, #1]. Biochemical profiling of the recombinant catalytic domain with a positional scanning substrate library established it as a functional SUMO protease whose cleavage-sequence preference is distinct from that of human SENPs [#0]. In reconstituted in vitro assays, SENP1 performs both arms of SUMO metabolism: it deconjugates SUMO-1 from modified RanGAP1 (isopeptidase/deSUMOylase activity) and processes SUMO precursors to their mature form (maturation activity) [#1]. Its enzymatic activity is required for the intraerythrocytic cycle: aza-epoxide small-molecule inhibitors (most potent VEA-260) block recombinant SENP1 activity and P. falciparum replication in human erythrocytes, with parasite clearance tracking inhibitor potency, and the most potent compound disrupts late schizont morphology and prevents egress from the red blood cell [#2]. In P. berghei, proximity labeling places SENP1 in the vicinity of the nuclear pore complex [#4]. Beyond these findings, the direct substrates, structural basis, and genetic loss-of-function phenotype of SENP1 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before mechanistic work could proceed, it was unknown whether SENP1 could be produced as folded, homogeneous protein; establishing a purification route enabled all downstream biochemistry.\",\n      \"evidence\": \"Recombinant expression in E. coli via a CPD-His6 fusion tag, affinity and gel-filtration purification, and growth of diffraction-quality crystals\",\n      \"pmids\": [\"19956581\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystal structure was reported despite diffraction-quality crystals\", \"Purification demonstrates feasibility but establishes no catalytic or biological function\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unknown whether SENP1 is a genuine SUMO protease and how its specificity compares to human enzymes; profiling defined it as a functional SUMO-specific protease with a unique cleavage preference, marking it as biochemically distinct from human SENPs.\",\n      \"evidence\": \"Recombinant catalytic domain assayed with a positional scanning substrate library (in vitro)\",\n      \"pmids\": [\"21700207\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Distinct specificity does not identify the endogenous parasite substrates\", \"Assay used a synthetic library rather than native Plasmodium SUMO conjugates\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"To confirm SENP1 carries out canonical SUMO-cycle chemistry, both its deconjugating and precursor-maturation activities were tested; it cleaved SUMO-1 from RanGAP1 and processed SUMO precursors, establishing dual deSUMOylase and maturation functions.\",\n      \"evidence\": \"In vitro deSUMOylation assay with recombinant catalytic domain against SUMO-RanGAP1 and SUMO precursor substrates\",\n      \"pmids\": [\"21700207\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Activities shown on human SUMO-1/RanGAP1 substrates, not native Plasmodium SUMO conjugates\", \"Physiological substrates in the parasite remain unidentified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether SENP1 activity matters for parasite viability was unresolved; pharmacological inhibition linked its enzymatic activity to intraerythrocytic replication and schizont egress, nominating it as a target for blood-stage growth and RBC exit.\",\n      \"evidence\": \"Aza-epoxide inhibitor screen (VEA-260) with in vitro protease inhibition, P. falciparum erythrocyte replication assays, and morphological analysis of infected RBCs\",\n      \"pmids\": [\"21700207\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Target validation is pharmacological only, not genetic; inhibitor off-target effects not excluded\", \"Egress and morphology phenotypes are correlative to inhibition, not to defined SENP1 substrates\", \"No genetic knockout/knockdown phenotype established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether SENP1 has roles outside blood stages was unexplored; transcriptional upregulation in attenuated liver-stage sporozoites raised a possible stress/radiation-response role, though at the expression level only.\",\n      \"evidence\": \"Genome-wide microarray of γ-irradiation-attenuated intrahepatic P. falciparum sporozoites (day 3 post-infection)\",\n      \"pmids\": [\"27911910\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Transcript-only observation with no protein-level or functional follow-up on SENP1\", \"Causal link between SENP1 and stress response not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The subcellular context of SENP1 was undefined; proximity labeling of a nuclear pore scaffold placed it near the nuclear pore complex, hinting at a nuclear-envelope-associated context for its SUMO-processing activity.\",\n      \"evidence\": \"TurboID proximity labeling from P. berghei Nup313 followed by affinity purification and mass spectrometry\",\n      \"pmids\": [\"36040030\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Proximity labeling does not establish direct interaction or stable localization\", \"Shown in P. berghei, not confirmed for P. falciparum SENP1\", \"Functional consequence of nuclear-pore proximity untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous SUMOylated substrates of SENP1, its genetic loss-of-function phenotype, and the structural basis of its distinct specificity remain unresolved in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No native Plasmodium substrate identified\", \"No genetic knockout/knockdown phenotype\", \"No experimental structure despite crystallization feasibility\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0070139\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0004197\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016925\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0000387\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Nup313 (P. berghei nuclear pore complex scaffold; proximity-labeling proximity only) [#4]\"\n    ],\n    \"other_free_text\": [\n      \"Recombinant catalytic domain cleaves human SUMO-1 from RanGAP1 in vitro; endogenous Plasmodium substrates unidentified [#1]\",\n      \"Cleavage-sequence preference distinct from human SENPs [#0]\",\n      \"Aza-epoxide inhibitor VEA-260 blocks enzymatic activity, parasite replication, schizont maturation, and RBC egress (pharmacological, not genetic, validation) [#2]\",\n      \"Transcript upregulated ~5.4-fold in γ-irradiation-attenuated liver-stage sporozoites (expression data only) [#5]\",\n      \"Purifiable as near-homogeneous recombinant protein yielding diffraction-quality crystals; no structure reported [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1233900","name":null,"product":"sentrin-specific protease 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1448500","name":null,"product":"sentrin-specific protease 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1453300","name":null,"product":"sentrin-specific protease 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SENP1","evaluation":null}