{"gene":"PF3D7_0711400","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2025,"finding":"SAP18 (PF3D7_0711400) in P. knowlesi undergoes lactate-induced lysine lactylation (KLa) at a unique site not found in the acetylome, detected by mass spectrometry in trophozoite cultures treated with 25 mM lactate. SAP18 is described as associated with HDAC1 in this context.","method":"Mass spectrometry-based proteomics (PTM profiling) of trophozoite cultures +/- lactate treatment","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — mass spectrometry directly identifies the PTM on SAP18 in a single study; no functional validation of the modification on SAP18 itself","pmids":["41417877"],"is_preprint":false,"attribution":[{"species":"Plasmodium knowlesi","strain":""}]},{"year":2018,"finding":"SAP18 (PF3D7_0711400) transcript abundance decreases upon cell cycle re-entry in P. falciparum following DFMO-induced G1 arrest and polyamine rescue, placing SAP18 expression as an early responder (RE1) that is downregulated at the G1/S transition.","method":"Gene expression analysis (transcriptomics) during controlled cell cycle arrest and re-entry using DFMO and polyamine supplementation","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single transcriptomic study, no direct protein-level or functional validation of SAP18's role in cell cycle control","pmids":["30409996"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"SAP18 (PF3D7_0711400) transcript abundance is increased during gametocyte development in P. falciparum, with its expression implicated in contributing to decreased DNA synthesis and a block in proliferation required for sexual differentiation.","method":"High-resolution transcriptome profiling across gametocyte developmental stages","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single transcriptomic study, no direct protein-level experiment or mechanistic validation for SAP18 specifically","pmids":["31795940"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0711400 (SAP18) is a putative histone deacetylase complex subunit in Plasmodium that is associated with HDAC1, undergoes lactate-induced lysine lactylation in P. knowlesi, and shows dynamic transcript regulation during cell cycle transitions and gametocyte development in P. falciparum, but no direct biochemical or structural characterization of its function has been reported."},"narrative":{"mechanistic_narrative":"PF3D7_0711400 (SAP18) is a putative histone deacetylase complex subunit in Plasmodium whose only direct biochemical characterization to date is its lactate-induced lysine lactylation: in P. knowlesi trophozoites treated with lactate, SAP18 acquires a lysine lactylation mark at a site unique to the lactylome (absent from the acetylome), and in this context it is described as associated with HDAC1 [PMID:41417877]. Beyond this association and PTM, the protein has not been functionally or structurally characterized in the available corpus, and no direct experiment establishes its role within the deacetylase complex. At the transcript level in P. falciparum, SAP18 mRNA shows dynamic regulation across cell-cycle and developmental transitions—downregulated as an early responder at the G1/S transition following DFMO-induced arrest and polyamine rescue [PMID:30409996], and upregulated during gametocyte development where it is implicated in reduced DNA synthesis and a proliferative block accompanying sexual differentiation [PMID:31795940]—but these are transcriptomic correlations rather than protein-level or mechanistic evidence for SAP18 function.","teleology":[{"year":2018,"claim":"To ask whether SAP18 participates in cell-cycle control, its transcript behavior was tracked through a controlled arrest-and-re-entry protocol, establishing it as an early transcriptional responder downregulated at the G1/S transition.","evidence":"Transcriptomics during DFMO-induced G1 arrest and polyamine-rescued cell-cycle re-entry in P. falciparum","pmids":["30409996"],"confidence":"Low","gaps":["Single transcriptomic study with no protein-level or functional validation of SAP18 in cell-cycle control","No evidence that the transcript change reflects a causal role rather than a downstream correlate","No link established between this transcript regulation and SAP18's role in a deacetylase complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"To probe SAP18's involvement in sexual differentiation, its expression was profiled across gametocyte development, showing upregulation coincident with decreased DNA synthesis and a proliferative block.","evidence":"High-resolution transcriptome profiling across gametocyte developmental stages in P. falciparum","pmids":["31795940"],"confidence":"Low","gaps":["Correlative transcriptomics only; no direct experiment tests SAP18's role in the proliferation block","No protein-level or mechanistic validation for SAP18 specifically","Causal contribution to sexual differentiation not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To determine whether SAP18 is a direct target of lactate-driven modification, PTM proteomics identified a unique lysine lactylation site on SAP18 in lactate-treated trophozoites, providing the first direct protein-level evidence for the gene and linking it to HDAC1 association.","evidence":"Mass spectrometry-based PTM proteomics of P. knowlesi trophozoite cultures +/- 25 mM lactate","pmids":["41417877"],"confidence":"Medium","gaps":["No functional validation of the lactylation mark on SAP18 itself","The HDAC1 association is described but not biochemically mapped or reciprocally validated for SAP18","Functional consequence of the modification for deacetylase complex activity is unknown"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]},{"year":null,"claim":"Whether SAP18 has a defined biochemical activity, a mapped role within a Plasmodium HDAC complex, or a causal function in the cell-cycle and gametocyte phenotypes it correlates with remains unresolved.","evidence":"No direct biochemical, genetic, or structural characterization of SAP18 function reported in the corpus","pmids":[],"confidence":"Low","gaps":["No knockout, knockdown, or complementation study of SAP18","No structural or reconstitution data for SAP18 or its complex membership","No demonstration that transcript-level correlations reflect protein-level SAP18 function"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Associated with HDAC1 (histone deacetylase complex) [#0]"],"partners":["HDAC1 [#0]"],"other_free_text":["Undergoes lactate-induced lysine lactylation at a site unique to the lactylome in P. knowlesi trophozoites [#0]","Transcript downregulated as an early responder at the G1/S transition in P. falciparum [#1]","Transcript upregulated during P. falciparum gametocyte development, implicated in decreased DNA synthesis and proliferative block [#2]","No direct biochemical or structural characterization of SAP18 function reported in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15256513","id":"PMC_15256513","title":"Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum.","date":"2004","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/15256513","citation_count":192,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41417877","id":"","title":"Histone lactylation: A new epigenetic mark in the malaria parasite Plasmodium.","date":"2025","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41417877","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAP18"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31795940","id":"","title":"Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation.","date":"2019","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/31795940","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAP18"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30409996","id":"","title":"Inducing controlled cell cycle arrest and re-entry during asexual proliferation of Plasmodium falciparum malaria parasites.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30409996","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAP18"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6638,"output_tokens":841,"usd":0.016265,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5533,"output_tokens":1906,"usd":0.037657,"stage2_stop_reason":"end_turn"},"total_usd":0.053922,"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\": 2025,\n      \"finding\": \"SAP18 (PF3D7_0711400) in P. knowlesi undergoes lactate-induced lysine lactylation (KLa) at a unique site not found in the acetylome, detected by mass spectrometry in trophozoite cultures treated with 25 mM lactate. SAP18 is described as associated with HDAC1 in this context.\",\n      \"method\": \"Mass spectrometry-based proteomics (PTM profiling) of trophozoite cultures +/- lactate treatment\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — mass spectrometry directly identifies the PTM on SAP18 in a single study; no functional validation of the modification on SAP18 itself\",\n      \"pmids\": [\"41417877\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SAP18 (PF3D7_0711400) transcript abundance decreases upon cell cycle re-entry in P. falciparum following DFMO-induced G1 arrest and polyamine rescue, placing SAP18 expression as an early responder (RE1) that is downregulated at the G1/S transition.\",\n      \"method\": \"Gene expression analysis (transcriptomics) during controlled cell cycle arrest and re-entry using DFMO and polyamine supplementation\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single transcriptomic study, no direct protein-level or functional validation of SAP18's role in cell cycle control\",\n      \"pmids\": [\"30409996\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SAP18 (PF3D7_0711400) transcript abundance is increased during gametocyte development in P. falciparum, with its expression implicated in contributing to decreased DNA synthesis and a block in proliferation required for sexual differentiation.\",\n      \"method\": \"High-resolution transcriptome profiling across gametocyte developmental stages\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single transcriptomic study, no direct protein-level experiment or mechanistic validation for SAP18 specifically\",\n      \"pmids\": [\"31795940\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0711400 (SAP18) is a putative histone deacetylase complex subunit in Plasmodium that is associated with HDAC1, undergoes lactate-induced lysine lactylation in P. knowlesi, and shows dynamic transcript regulation during cell cycle transitions and gametocyte development in P. falciparum, but no direct biochemical or structural characterization of its function has been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0711400 (SAP18) is a putative histone deacetylase complex subunit in Plasmodium whose only direct biochemical characterization to date is its lactate-induced lysine lactylation: in P. knowlesi trophozoites treated with lactate, SAP18 acquires a lysine lactylation mark at a site unique to the lactylome (absent from the acetylome), and in this context it is described as associated with HDAC1 [#0]. Beyond this association and PTM, the protein has not been functionally or structurally characterized in the available corpus, and no direct experiment establishes its role within the deacetylase complex. At the transcript level in P. falciparum, SAP18 mRNA shows dynamic regulation across cell-cycle and developmental transitions—downregulated as an early responder at the G1/S transition following DFMO-induced arrest and polyamine rescue [#1], and upregulated during gametocyte development where it is implicated in reduced DNA synthesis and a proliferative block accompanying sexual differentiation [#2]—but these are transcriptomic correlations rather than protein-level or mechanistic evidence for SAP18 function.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To ask whether SAP18 participates in cell-cycle control, its transcript behavior was tracked through a controlled arrest-and-re-entry protocol, establishing it as an early transcriptional responder downregulated at the G1/S transition.\",\n      \"evidence\": \"Transcriptomics during DFMO-induced G1 arrest and polyamine-rescued cell-cycle re-entry in P. falciparum\",\n      \"pmids\": [\"30409996\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single transcriptomic study with no protein-level or functional validation of SAP18 in cell-cycle control\",\n        \"No evidence that the transcript change reflects a causal role rather than a downstream correlate\",\n        \"No link established between this transcript regulation and SAP18's role in a deacetylase complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"To probe SAP18's involvement in sexual differentiation, its expression was profiled across gametocyte development, showing upregulation coincident with decreased DNA synthesis and a proliferative block.\",\n      \"evidence\": \"High-resolution transcriptome profiling across gametocyte developmental stages in P. falciparum\",\n      \"pmids\": [\"31795940\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Correlative transcriptomics only; no direct experiment tests SAP18's role in the proliferation block\",\n        \"No protein-level or mechanistic validation for SAP18 specifically\",\n        \"Causal contribution to sexual differentiation not demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To determine whether SAP18 is a direct target of lactate-driven modification, PTM proteomics identified a unique lysine lactylation site on SAP18 in lactate-treated trophozoites, providing the first direct protein-level evidence for the gene and linking it to HDAC1 association.\",\n      \"evidence\": \"Mass spectrometry-based PTM proteomics of P. knowlesi trophozoite cultures +/- 25 mM lactate\",\n      \"pmids\": [\"41417877\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional validation of the lactylation mark on SAP18 itself\",\n        \"The HDAC1 association is described but not biochemically mapped or reciprocally validated for SAP18\",\n        \"Functional consequence of the modification for deacetylase complex activity is unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether SAP18 has a defined biochemical activity, a mapped role within a Plasmodium HDAC complex, or a causal function in the cell-cycle and gametocyte phenotypes it correlates with remains unresolved.\",\n      \"evidence\": \"No direct biochemical, genetic, or structural characterization of SAP18 function reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout, knockdown, or complementation study of SAP18\",\n        \"No structural or reconstitution data for SAP18 or its complex membership\",\n        \"No demonstration that transcript-level correlations reflect protein-level SAP18 function\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"Associated with HDAC1 (histone deacetylase complex) [#0]\"],\n    \"partners\": [\"HDAC1 [#0]\"],\n    \"other_free_text\": [\n      \"Undergoes lactate-induced lysine lactylation at a site unique to the lactylome in P. knowlesi trophozoites [#0]\",\n      \"Transcript downregulated as an early responder at the G1/S transition in P. falciparum [#1]\",\n      \"Transcript upregulated during P. falciparum gametocyte development, implicated in decreased DNA synthesis and proliferative block [#2]\",\n      \"No direct biochemical or structural characterization of SAP18 function reported in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0711400","name":null,"product":"histone deacetylase complex subunit SAP18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1222000","name":null,"product":"histone deacetylase complex subunit SAP18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0110100","name":null,"product":"histone deacetylase complex subunit SAP18, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SAP18","evaluation":null}