{"gene":"PF3D7_1464900","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_1464900 (ATP-dependent zinc metalloprotease FtsH) was identified as a component of the apicoplast proteome in P. falciparum using proximity biotinylation (BioID) combined with machine learning, placing it within the apicoplast organelle.","method":"Proximity biotinylation proteomics (BioID) combined with machine learning classification","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — BioID-based proteomics is a solid proximity method, but FtsH is listed as one of 346 proteins without specific functional validation of this individual protein; single study","pmids":["30212465"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"P. falciparum FtsH (PF3D7_1464900), a zinc-dependent metalloprotease, was identified as a likely interaction partner of stomatin-like protein (STOML) by pulldown experiments. The complex localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network, analogous to the bacterial HflK/C vault-like structure around FtsH hexamers.","method":"Pulldown/co-immunoprecipitation of epitope-tagged STOML followed by mass spectrometry; AlphaFold2 structural prediction for complex modeling; live imaging of epitope-tagged endogenous proteins","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single pulldown identifying FtsH as interaction partner with supporting structural prediction and localization data, but no reciprocal Co-IP or in vitro reconstitution of FtsH enzymatic activity; single lab","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1464900 (FtsH) is a zinc-dependent AAA+ metalloprotease that localizes to the P. falciparum mitochondrion (and is also predicted in the apicoplast proteome), where it forms a putative large protein complex with the stomatin-like protein STOML at distinct puncta on mitochondrial branching points, consistent with a role analogous to the bacterial HflK/C–FtsH vault complex, though its specific enzymatic substrates and precise functional contribution to blood-stage development remain uncharacterized."},"narrative":{"mechanistic_narrative":"PF3D7_1464900 is a putative ATP-dependent zinc metalloprotease of the FtsH family in Plasmodium falciparum, associated with the parasite's organellar membrane systems. It was recovered in the apicoplast proteome by proximity biotinylation, placing it within that organelle [PMID:30212465], and it co-purifies with the stomatin-like protein STOML, with the complex localizing to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network in an arrangement modeled as analogous to the bacterial HflK/C vault-like structure around FtsH hexamers [PMID:41662436]. Beyond this organellar localization and the STOML association [PMID:30212465, PMID:41662436], the enzymatic substrates, catalytic activity, and functional contribution of PF3D7_1464900 to blood-stage development have not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where this putative protease resides was the first step; proteomic mapping placed PF3D7_1464900 in the apicoplast, giving it an organellar context.","evidence":"Proximity biotinylation (BioID) proteomics with machine-learning classification of the apicoplast proteome","pmids":["30212465"],"confidence":"Medium","gaps":["FtsH listed among 346 proteins without individual functional validation","No evidence of catalytic activity or substrate","Apicoplast assignment not cross-validated against mitochondrial localization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Identifying a binding partner and its subcellular distribution addressed whether PF3D7_1464900 acts within a defined complex; pulldowns and imaging linked it to STOML at discrete mitochondrial-network puncta, invoking a bacterial HflK/C-FtsH vault analogy.","evidence":"Co-IP/pulldown of epitope-tagged STOML with mass spectrometry, AlphaFold2 complex modeling, and live imaging of endogenous epitope-tagged proteins","pmids":["41662436"],"confidence":"Medium","gaps":["Single pulldown without reciprocal Co-IP or in vitro reconstitution of the complex","FtsH zinc-metalloprotease activity not biochemically demonstrated","Apparent mitochondrial localization here contrasts with the earlier apicoplast assignment; dual/definitive targeting unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The enzymatic substrates, catalytic activity, and functional requirement of PF3D7_1464900 for parasite development remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No substrate identified for the putative protease","No genetic knockout/knockdown phenotype established","Enzymatic zinc-metalloprotease activity not directly measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["STOML-FtsH complex (HflK/C-FtsH vault-like analog)"],"partners":["STOML (STOMATIN-LIKE PROTEIN)"],"other_free_text":["Localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network [#1]","Recovered in apicoplast proteome by BioID [#0]; organellar assignment differs between the two studies","Enzymatic substrates and functional contribution to blood-stage development uncharacterized in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30212465","id":"PMC_30212465","title":"Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites.","date":"2018","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/30212465","citation_count":85,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32169021","id":"PMC_32169021","title":"The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.","date":"2020","source":"Annual review of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32169021","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33497624","id":"PMC_33497624","title":"Structure, function, and substrates of Clp AAA+ protease systems in cyanobacteria, plastids, and apicoplasts: A comparative analysis.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33497624","citation_count":58,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP","FTSH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41662436","id":"PMC_41662436","title":"Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41662436","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FTSH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4744,"output_tokens":706,"usd":0.012411,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5307,"output_tokens":1637,"usd":0.03373,"stage2_stop_reason":"end_turn"},"total_usd":0.046141,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PF3D7_1464900 (ATP-dependent zinc metalloprotease FtsH) was identified as a component of the apicoplast proteome in P. falciparum using proximity biotinylation (BioID) combined with machine learning, placing it within the apicoplast organelle.\",\n      \"method\": \"Proximity biotinylation proteomics (BioID) combined with machine learning classification\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — BioID-based proteomics is a solid proximity method, but FtsH is listed as one of 346 proteins without specific functional validation of this individual protein; single study\",\n      \"pmids\": [\"30212465\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"P. falciparum FtsH (PF3D7_1464900), a zinc-dependent metalloprotease, was identified as a likely interaction partner of stomatin-like protein (STOML) by pulldown experiments. The complex localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network, analogous to the bacterial HflK/C vault-like structure around FtsH hexamers.\",\n      \"method\": \"Pulldown/co-immunoprecipitation of epitope-tagged STOML followed by mass spectrometry; AlphaFold2 structural prediction for complex modeling; live imaging of epitope-tagged endogenous proteins\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single pulldown identifying FtsH as interaction partner with supporting structural prediction and localization data, but no reciprocal Co-IP or in vitro reconstitution of FtsH enzymatic activity; single lab\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1464900 (FtsH) is a zinc-dependent AAA+ metalloprotease that localizes to the P. falciparum mitochondrion (and is also predicted in the apicoplast proteome), where it forms a putative large protein complex with the stomatin-like protein STOML at distinct puncta on mitochondrial branching points, consistent with a role analogous to the bacterial HflK/C–FtsH vault complex, though its specific enzymatic substrates and precise functional contribution to blood-stage development remain uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1464900 is a putative ATP-dependent zinc metalloprotease of the FtsH family in Plasmodium falciparum, associated with the parasite's organellar membrane systems. It was recovered in the apicoplast proteome by proximity biotinylation, placing it within that organelle [#0], and it co-purifies with the stomatin-like protein STOML, with the complex localizing to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network in an arrangement modeled as analogous to the bacterial HflK/C vault-like structure around FtsH hexamers [#1]. Beyond this organellar localization and the STOML association [#0, #1], the enzymatic substrates, catalytic activity, and functional contribution of PF3D7_1464900 to blood-stage development have not been characterized in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where this putative protease resides was the first step; proteomic mapping placed PF3D7_1464900 in the apicoplast, giving it an organellar context.\",\n      \"evidence\": \"Proximity biotinylation (BioID) proteomics with machine-learning classification of the apicoplast proteome\",\n      \"pmids\": [\"30212465\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"FtsH listed among 346 proteins without individual functional validation\",\n        \"No evidence of catalytic activity or substrate\",\n        \"Apicoplast assignment not cross-validated against mitochondrial localization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identifying a binding partner and its subcellular distribution addressed whether PF3D7_1464900 acts within a defined complex; pulldowns and imaging linked it to STOML at discrete mitochondrial-network puncta, invoking a bacterial HflK/C-FtsH vault analogy.\",\n      \"evidence\": \"Co-IP/pulldown of epitope-tagged STOML with mass spectrometry, AlphaFold2 complex modeling, and live imaging of endogenous epitope-tagged proteins\",\n      \"pmids\": [\"41662436\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single pulldown without reciprocal Co-IP or in vitro reconstitution of the complex\",\n        \"FtsH zinc-metalloprotease activity not biochemically demonstrated\",\n        \"Apparent mitochondrial localization here contrasts with the earlier apicoplast assignment; dual/definitive targeting unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The enzymatic substrates, catalytic activity, and functional requirement of PF3D7_1464900 for parasite development remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No substrate identified for the putative protease\",\n        \"No genetic knockout/knockdown phenotype established\",\n        \"Enzymatic zinc-metalloprotease activity not directly measured\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004222\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\n      \"STOML-FtsH complex (HflK/C-FtsH vault-like analog)\"\n    ],\n    \"partners\": [\n      \"STOML (stomatin-like protein)\"\n    ],\n    \"other_free_text\": [\n      \"Localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network [#1]\",\n      \"Recovered in apicoplast proteome by BioID [#0]; organellar assignment differs between the two studies\",\n      \"Enzymatic substrates and functional contribution to blood-stage development uncharacterized in the available corpus\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1464900","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_0813700, PF3D7_0318100, PF3D7_0416600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1464900","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1328300","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1216600","name":null,"product":"ATP-dependent zinc metalloprotease FTSH, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}