{"gene":"PF3D7_0807700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2014,"finding":"PF3D7_0807700 (DegP) complements the growth defect of an E. coli degP null mutant at non-permissive temperatures and confers resistance to oxidative stress, demonstrating functional serine protease and chaperone activities in thermo-oxidative stress protection.","method":"Complementation of E. coli degP null mutant with PfdegP gene; growth assays at non-permissive temperatures and under oxidative stress conditions","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — heterologous complementation assay with defined phenotypic readout; single lab but multiple orthogonal methods (complementation + co-IP + SPR + co-localization)","pmids":["24494818"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PF3D7_0807700 (DegP) physically interacts with P. falciparum Hsp70, iron superoxide dismutase (PfSod), enolase (PfEno), ornithine aminotransferase (PfOat), lactate dehydrogenase (PfLDH), and glucose-6-phosphate isomerase (PfGpi), forming a multi-protein complex; interactions confirmed by co-immunoprecipitation and surface plasmon resonance.","method":"Anti-bait co-immunoprecipitation; surface plasmon resonance (SPR); co-sedimentation through density gradient; fluorescence microscopy co-localization","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding confirmed by both Co-IP and SPR in single lab with multiple orthogonal methods","pmids":["24494818"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"DegP expression in P. falciparum is significantly induced upon heat shock and oxidative stress, and the protein co-localizes with PfHsp70 and PfEno, consistent with a role in stress-response protein quality control in an extra-cytoplasmic compartment.","method":"Western blot quantification of DegP under stress conditions; fluorescence microscopy co-localization; density-gradient co-sedimentation","journal":"The FEBS journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, localization and expression induction shown but no direct functional consequence of localization established","pmids":["24494818"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Deletion of PF3D7_0807700 (DegP; the P. falciparum homolog of T. gondii DegP2) lowers cellular heme levels and decreases susceptibility to dihydroartemisinin (DHA), placing DegP in the heme metabolism pathway that modulates artemisinin susceptibility.","method":"CRISPR-based gene deletion of PfDegP in P. falciparum; porphyrin/heme quantification; DHA susceptibility assays (IC50 shift)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined biochemical (heme levels) and pharmacological (DHA IC50) phenotype readouts; single lab, supported by parallel T. gondii screen","pmids":["32968076"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0807700 (DegP) is a secretory serine protease with chaperone activity that forms a complex with PfHsp70, PfSod, PfEno, and other partners to protect P. falciparum against thermo-oxidative stress, and its disruption lowers heme levels and reduces dihydroartemisinin susceptibility, placing it within the heme metabolism pathway."},"narrative":{"mechanistic_narrative":"PF3D7_0807700 (DegP) is a Plasmodium falciparum serine protease with an associated chaperone activity that functions in protection against thermo-oxidative stress; heterologous expression of PfDegP rescues the temperature-sensitive growth defect and oxidative-stress hypersensitivity of an E. coli degP null mutant, establishing that it retains both protease and chaperone functions [PMID:24494818]. In the parasite, DegP assembles into a multi-protein complex with PfHsp70, iron superoxide dismutase (PfSod), enolase (PfEno), ornithine aminotransferase (PfOat), lactate dehydrogenase (PfLDH), and glucose-6-phosphate isomerase (PfGpi), with binding confirmed by co-immunoprecipitation and surface plasmon resonance [PMID:24494818]. Consistent with a stress-response role, DegP expression is induced by heat shock and oxidative stress and the protein co-localizes with PfHsp70 and PfEno in an extra-cytoplasmic compartment [PMID:24494818]. Independently, CRISPR-based deletion of PfDegP lowers cellular heme levels and decreases parasite susceptibility to dihydroartemisinin, linking DegP to the heme metabolism pathway that modulates artemisinin action [PMID:32968076]. Beyond these findings, the specific proteolytic substrates of DegP and the mechanism connecting its stress-protective complex to heme levels have not been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Whether the P. falciparum DegP homolog retains functional protease and chaperone activity was unknown; heterologous complementation established that it does and links it to thermo-oxidative stress defense.","evidence":"Complementation of an E. coli degP null mutant with PfdegP, with growth assays at non-permissive temperature and under oxidative stress","pmids":["24494818"],"confidence":"Medium","gaps":["Activity shown only in a heterologous E. coli system, not by direct in vitro proteolysis of a defined substrate","No native protease substrate in P. falciparum identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The molecular context of DegP was undefined; identifying its binding partners placed it within a multi-protein complex spanning chaperone, antioxidant, and metabolic enzymes.","evidence":"Anti-bait co-immunoprecipitation and surface plasmon resonance, with density-gradient co-sedimentation, in P. falciparum","pmids":["24494818"],"confidence":"Medium","gaps":["Stoichiometry and architecture of the complex not resolved","Functional consequence of each interaction (e.g. whether partners are substrates or regulators) not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Whether DegP behaves as a stress-response factor in the parasite was untested; stress-induced expression and co-localization support a protein quality-control role in an extra-cytoplasmic compartment.","evidence":"Western blot quantification under heat shock and oxidative stress plus fluorescence co-localization with PfHsp70 and PfEno in P. falciparum","pmids":["24494818"],"confidence":"Low","gaps":["Localization and expression induction shown but no direct functional consequence of the localization established","Precise subcellular compartment not molecularly defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether DegP has a role in drug response was unknown; gene deletion connected it to heme metabolism and artemisinin susceptibility.","evidence":"CRISPR-based deletion of PfDegP with heme/porphyrin quantification and dihydroartemisinin IC50 assays in P. falciparum","pmids":["32968076"],"confidence":"Medium","gaps":["Mechanism linking DegP loss to reduced heme is not resolved","Whether the DHA-susceptibility change reflects protease activity or the stress complex is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The native proteolytic substrates of DegP and the mechanistic bridge between its stress-protective complex and heme homeostasis remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No endogenous protease substrate identified","No structural model of the DegP complex","Causal chain from DegP loss to lowered heme and altered DHA response undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["DegP-PfHsp70-PfSod-PfEno-PfOat-PfLDH-PfGpi multi-protein stress-response complex [#1]"],"partners":["PFHSP70 [#1, #2]","PFSOD (IRON SUPEROXIDE DISMUTASE) [#1]","PFENO (ENOLASE) [#1, #2]","PFOAT (ORNITHINE AMINOTRANSFERASE) [#1]","PFLDH (LACTATE DEHYDROGENASE) [#1]","PFGPI (GLUCOSE-6-PHOSPHATE ISOMERASE) [#1]"],"other_free_text":["Deletion of DegP lowers cellular heme and reduces dihydroartemisinin susceptibility, linking it to heme metabolism [#3]","Expression induced by heat shock and oxidative stress [#2]","Functionally complements E. coli degP null mutant [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32968076","id":"PMC_32968076","title":"Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32968076","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfDegP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24494818","id":"PMC_24494818","title":"A secretory multifunctional serine protease, DegP of Plasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development.","date":"2014","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/24494818","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DegP","serine protease DegP","PfDegP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34066964","id":"PMC_34066964","title":"Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP.","date":"2021","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34066964","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DegP","serine protease DegP","PfDegP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27491850","id":"PMC_27491850","title":"In-silico studies on DegP protein of Plasmodium falciparum in search of anti-malarials.","date":"2016","source":"Journal of molecular modeling","url":"https://pubmed.ncbi.nlm.nih.gov/27491850","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DegP","PfDegP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4886,"output_tokens":1185,"usd":0.016216,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5975,"output_tokens":2305,"usd":0.04375,"stage2_stop_reason":"end_turn"},"total_usd":0.059966,"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\": 2014,\n      \"finding\": \"PF3D7_0807700 (DegP) complements the growth defect of an E. coli degP null mutant at non-permissive temperatures and confers resistance to oxidative stress, demonstrating functional serine protease and chaperone activities in thermo-oxidative stress protection.\",\n      \"method\": \"Complementation of E. coli degP null mutant with PfdegP gene; growth assays at non-permissive temperatures and under oxidative stress conditions\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — heterologous complementation assay with defined phenotypic readout; single lab but multiple orthogonal methods (complementation + co-IP + SPR + co-localization)\",\n      \"pmids\": [\"24494818\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PF3D7_0807700 (DegP) physically interacts with P. falciparum Hsp70, iron superoxide dismutase (PfSod), enolase (PfEno), ornithine aminotransferase (PfOat), lactate dehydrogenase (PfLDH), and glucose-6-phosphate isomerase (PfGpi), forming a multi-protein complex; interactions confirmed by co-immunoprecipitation and surface plasmon resonance.\",\n      \"method\": \"Anti-bait co-immunoprecipitation; surface plasmon resonance (SPR); co-sedimentation through density gradient; fluorescence microscopy co-localization\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding confirmed by both Co-IP and SPR in single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24494818\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DegP expression in P. falciparum is significantly induced upon heat shock and oxidative stress, and the protein co-localizes with PfHsp70 and PfEno, consistent with a role in stress-response protein quality control in an extra-cytoplasmic compartment.\",\n      \"method\": \"Western blot quantification of DegP under stress conditions; fluorescence microscopy co-localization; density-gradient co-sedimentation\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, localization and expression induction shown but no direct functional consequence of localization established\",\n      \"pmids\": [\"24494818\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Deletion of PF3D7_0807700 (DegP; the P. falciparum homolog of T. gondii DegP2) lowers cellular heme levels and decreases susceptibility to dihydroartemisinin (DHA), placing DegP in the heme metabolism pathway that modulates artemisinin susceptibility.\",\n      \"method\": \"CRISPR-based gene deletion of PfDegP in P. falciparum; porphyrin/heme quantification; DHA susceptibility assays (IC50 shift)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined biochemical (heme levels) and pharmacological (DHA IC50) phenotype readouts; single lab, supported by parallel T. gondii screen\",\n      \"pmids\": [\"32968076\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0807700 (DegP) is a secretory serine protease with chaperone activity that forms a complex with PfHsp70, PfSod, PfEno, and other partners to protect P. falciparum against thermo-oxidative stress, and its disruption lowers heme levels and reduces dihydroartemisinin susceptibility, placing it within the heme metabolism pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0807700 (DegP) is a Plasmodium falciparum serine protease with an associated chaperone activity that functions in protection against thermo-oxidative stress; heterologous expression of PfDegP rescues the temperature-sensitive growth defect and oxidative-stress hypersensitivity of an E. coli degP null mutant, establishing that it retains both protease and chaperone functions [#0]. In the parasite, DegP assembles into a multi-protein complex with PfHsp70, iron superoxide dismutase (PfSod), enolase (PfEno), ornithine aminotransferase (PfOat), lactate dehydrogenase (PfLDH), and glucose-6-phosphate isomerase (PfGpi), with binding confirmed by co-immunoprecipitation and surface plasmon resonance [#1]. Consistent with a stress-response role, DegP expression is induced by heat shock and oxidative stress and the protein co-localizes with PfHsp70 and PfEno in an extra-cytoplasmic compartment [#2]. Independently, CRISPR-based deletion of PfDegP lowers cellular heme levels and decreases parasite susceptibility to dihydroartemisinin, linking DegP to the heme metabolism pathway that modulates artemisinin action [#3]. Beyond these findings, the specific proteolytic substrates of DegP and the mechanism connecting its stress-protective complex to heme levels have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether the P. falciparum DegP homolog retains functional protease and chaperone activity was unknown; heterologous complementation established that it does and links it to thermo-oxidative stress defense.\",\n      \"evidence\": \"Complementation of an E. coli degP null mutant with PfdegP, with growth assays at non-permissive temperature and under oxidative stress\",\n      \"pmids\": [\"24494818\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Activity shown only in a heterologous E. coli system, not by direct in vitro proteolysis of a defined substrate\", \"No native protease substrate in P. falciparum identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The molecular context of DegP was undefined; identifying its binding partners placed it within a multi-protein complex spanning chaperone, antioxidant, and metabolic enzymes.\",\n      \"evidence\": \"Anti-bait co-immunoprecipitation and surface plasmon resonance, with density-gradient co-sedimentation, in P. falciparum\",\n      \"pmids\": [\"24494818\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and architecture of the complex not resolved\", \"Functional consequence of each interaction (e.g. whether partners are substrates or regulators) not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether DegP behaves as a stress-response factor in the parasite was untested; stress-induced expression and co-localization support a protein quality-control role in an extra-cytoplasmic compartment.\",\n      \"evidence\": \"Western blot quantification under heat shock and oxidative stress plus fluorescence co-localization with PfHsp70 and PfEno in P. falciparum\",\n      \"pmids\": [\"24494818\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Localization and expression induction shown but no direct functional consequence of the localization established\", \"Precise subcellular compartment not molecularly defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether DegP has a role in drug response was unknown; gene deletion connected it to heme metabolism and artemisinin susceptibility.\",\n      \"evidence\": \"CRISPR-based deletion of PfDegP with heme/porphyrin quantification and dihydroartemisinin IC50 assays in P. falciparum\",\n      \"pmids\": [\"32968076\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking DegP loss to reduced heme is not resolved\", \"Whether the DHA-susceptibility change reflects protease activity or the stress complex is unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The native proteolytic substrates of DegP and the mechanistic bridge between its stress-protective complex and heme homeostasis remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No endogenous protease substrate identified\", \"No structural model of the DegP complex\", \"Causal chain from DegP loss to lowered heme and altered DHA response undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004252\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006979\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0042168\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"DegP-PfHsp70-PfSod-PfEno-PfOat-PfLDH-PfGpi multi-protein stress-response complex [#1]\"\n    ],\n    \"partners\": [\n      \"PfHsp70 [#1, #2]\",\n      \"PfSod (iron superoxide dismutase) [#1]\",\n      \"PfEno (enolase) [#1, #2]\",\n      \"PfOat (ornithine aminotransferase) [#1]\",\n      \"PfLDH (lactate dehydrogenase) [#1]\",\n      \"PfGpi (glucose-6-phosphate isomerase) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"Deletion of DegP lowers cellular heme and reduces dihydroartemisinin susceptibility, linking it to heme metabolism [#3]\",\n      \"Expression induced by heat shock and oxidative stress [#2]\",\n      \"Functionally complements E. coli degP null mutant [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0807700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0818900, PF3D7_1324900). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0807700","name":null,"product":"serine protease DegP","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DegP","evaluation":null}