{"gene":"PF3D7_1115900","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2016,"finding":"PfDHHC9 (PF3D7_1115900) localizes to distinct organelles in P. falciparum schizonts, and its disruption has no effect on blood-stage growth but significantly reduces gametocyte formation, establishing a stage-specific role in gametocytogenesis.","method":"Endogenous tagging for localization; knockout/disruption studies with phenotypic readout (blood-stage growth and gametocyte formation assays)","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct gene knockout with defined cellular phenotype (gametocytogenesis) and localization by tagging, single lab with two orthogonal methods","pmids":["27060339"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"PfDHHC9 (PF3D7_1115900) exhibits palmitoyl-transferase enzymatic activity capable of palmitoylating P. falciparum substrates in vitro, as demonstrated by a palmitoyl-transferase activity assay adapted for P. falciparum; multiple DHHCs including PfDHHC9 can palmitoylate the same substrate, indicating functional redundancy in vitro.","method":"In vitro palmitoyl-transferase activity assay using recombinant P. falciparum DHHC proteins and P. falciparum substrates","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay establishing catalytic activity, but single lab and single method","pmids":["27060339"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"In P. berghei, deletion of DHHC9 alone produces a detectable phenotype that is enhanced when combined with deletion of DHHC3, revealing functional overlap and compensational relationships between PbDHHC9 and PbDHHC3 in gliding motility-related processes.","method":"Double knockout (DHHC3/DHHC9) generation with in vivo phenotypic comparison to single knockouts","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic epistasis via double knockout in a single study; the specific molecular mechanism of DHHC9's contribution is not resolved from the abstract alone","pmids":["27084458"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"DHHC9 (PF3D7_1115900) is a catalytically active palmitoyl-S-acyl transferase in P. falciparum that localizes to distinct organelles in schizonts, is dispensable for asexual blood-stage growth but required for efficient gametocyte formation, and in P. berghei shows functional overlap with DHHC3 in the context of gliding motility-associated palmitoylation."},"narrative":{"mechanistic_narrative":"DHHC9 (PF3D7_1115900) is a catalytically active palmitoyl-S-acyl transferase of Plasmodium falciparum with a stage-specific role in the parasite life cycle [PMID:27060339]. In an in vitro palmitoyl-transferase activity assay, recombinant PF3D7_1115900 palmitoylated P. falciparum substrates, and because multiple DHHC enzymes could modify the same substrate, its catalytic contribution overlaps with that of other family members in vitro [PMID:27060339]. In P. falciparum schizonts the enzyme localizes to distinct organelles, and while its disruption leaves asexual blood-stage growth unaffected, it significantly reduces gametocyte formation, indicating a selective requirement in gametocytogenesis rather than in asexual replication [PMID:27060339]. In P. berghei, deletion of the DHHC9 ortholog produces a phenotype that is enhanced by concurrent deletion of DHHC3, revealing functional overlap between the two enzymes in gliding motility-related processes [PMID:27084458]. Beyond these findings, the specific physiological substrates of PF3D7_1115900 and the molecular basis of its role in gametocytogenesis have not been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Whether PF3D7_1115900 is enzymatically functional was addressed by testing its catalytic activity directly, establishing it as a bona fide palmitoyl-transferase rather than an inferred family member.","evidence":"In vitro palmitoyl-transferase activity assay with recombinant P. falciparum DHHC proteins and parasite substrates","pmids":["27060339"],"confidence":"Medium","gaps":["No physiological substrate of PF3D7_1115900 identified in vivo","Redundancy in vitro leaves the enzyme's unique substrate specificity unresolved","Single lab, single method"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"The cellular role of PF3D7_1115900 was defined by asking where it acts and which life-cycle stage requires it, revealing a dispensable role in asexual growth but a requirement for efficient gametocytogenesis.","evidence":"Endogenous tagging for organellar localization plus gene disruption with blood-stage growth and gametocyte formation readouts in P. falciparum schizonts","pmids":["27060339"],"confidence":"Medium","gaps":["The molecular mechanism linking PF3D7_1115900 activity to gametocyte formation is unresolved","The specific organelles it localizes to are not molecularly identified","Substrates palmitoylated during gametocytogenesis are unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Whether DHHC9 acts alone or shares function with a sibling enzyme was tested genetically, showing functional overlap with DHHC3 in gliding motility-related processes in a rodent malaria model.","evidence":"Double knockout of DHHC3 and DHHC9 compared to single knockouts with in vivo phenotypic analysis in P. berghei","pmids":["27084458"],"confidence":"Low","gaps":["Genetic epistasis via double knockout in a single study; the specific molecular contribution of DHHC9 is not resolved","No substrate underlying the gliding motility phenotype identified","Relationship between the P. berghei motility role and the P. falciparum gametocyte role is untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The physiological substrates of PF3D7_1115900 and the mechanism by which its palmitoyl-transferase activity drives gametocytogenesis remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo substrate identified for PF3D7_1115900","Structural basis of catalysis and substrate selection uncharacterized","Mechanistic link between the enzyme and sexual-stage commitment undefined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["In P. falciparum schizonts, PF3D7_1115900 localizes to distinct (molecularly unidentified) organelles [#0].","PF3D7_1115900 disruption does not affect asexual blood-stage growth but significantly reduces gametocyte formation [#0].","Multiple DHHC enzymes can palmitoylate the same substrate as PF3D7_1115900 in vitro, indicating functional redundancy [#1].","In P. berghei, the DHHC9 ortholog shows functional overlap with DHHC3 in gliding motility-related processes, evidenced by an enhanced double-knockout phenotype [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23638681","id":"PMC_23638681","title":"Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion.","date":"2013","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/23638681","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27060339","id":"PMC_27060339","title":"Study of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27060339","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfDHHC9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27084458","id":"PMC_27084458","title":"Palmitoyl transferases have critical roles in the development of mosquito and liver stages of Plasmodium.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27084458","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DHHC9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4526,"output_tokens":910,"usd":0.013614,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5598,"output_tokens":1982,"usd":0.03877,"stage2_stop_reason":"end_turn"},"total_usd":0.052384,"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\": 2016,\n      \"finding\": \"PfDHHC9 (PF3D7_1115900) localizes to distinct organelles in P. falciparum schizonts, and its disruption has no effect on blood-stage growth but significantly reduces gametocyte formation, establishing a stage-specific role in gametocytogenesis.\",\n      \"method\": \"Endogenous tagging for localization; knockout/disruption studies with phenotypic readout (blood-stage growth and gametocyte formation assays)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct gene knockout with defined cellular phenotype (gametocytogenesis) and localization by tagging, single lab with two orthogonal methods\",\n      \"pmids\": [\"27060339\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PfDHHC9 (PF3D7_1115900) exhibits palmitoyl-transferase enzymatic activity capable of palmitoylating P. falciparum substrates in vitro, as demonstrated by a palmitoyl-transferase activity assay adapted for P. falciparum; multiple DHHCs including PfDHHC9 can palmitoylate the same substrate, indicating functional redundancy in vitro.\",\n      \"method\": \"In vitro palmitoyl-transferase activity assay using recombinant P. falciparum DHHC proteins and P. falciparum substrates\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay establishing catalytic activity, but single lab and single method\",\n      \"pmids\": [\"27060339\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In P. berghei, deletion of DHHC9 alone produces a detectable phenotype that is enhanced when combined with deletion of DHHC3, revealing functional overlap and compensational relationships between PbDHHC9 and PbDHHC3 in gliding motility-related processes.\",\n      \"method\": \"Double knockout (DHHC3/DHHC9) generation with in vivo phenotypic comparison to single knockouts\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic epistasis via double knockout in a single study; the specific molecular mechanism of DHHC9's contribution is not resolved from the abstract alone\",\n      \"pmids\": [\"27084458\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"DHHC9 (PF3D7_1115900) is a catalytically active palmitoyl-S-acyl transferase in P. falciparum that localizes to distinct organelles in schizonts, is dispensable for asexual blood-stage growth but required for efficient gametocyte formation, and in P. berghei shows functional overlap with DHHC3 in the context of gliding motility-associated palmitoylation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DHHC9 (PF3D7_1115900) is a catalytically active palmitoyl-S-acyl transferase of Plasmodium falciparum with a stage-specific role in the parasite life cycle [#0, #1]. In an in vitro palmitoyl-transferase activity assay, recombinant PF3D7_1115900 palmitoylated P. falciparum substrates, and because multiple DHHC enzymes could modify the same substrate, its catalytic contribution overlaps with that of other family members in vitro [#1]. In P. falciparum schizonts the enzyme localizes to distinct organelles, and while its disruption leaves asexual blood-stage growth unaffected, it significantly reduces gametocyte formation, indicating a selective requirement in gametocytogenesis rather than in asexual replication [#0]. In P. berghei, deletion of the DHHC9 ortholog produces a phenotype that is enhanced by concurrent deletion of DHHC3, revealing functional overlap between the two enzymes in gliding motility-related processes [#2]. Beyond these findings, the specific physiological substrates of PF3D7_1115900 and the molecular basis of its role in gametocytogenesis have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether PF3D7_1115900 is enzymatically functional was addressed by testing its catalytic activity directly, establishing it as a bona fide palmitoyl-transferase rather than an inferred family member.\",\n      \"evidence\": \"In vitro palmitoyl-transferase activity assay with recombinant P. falciparum DHHC proteins and parasite substrates\",\n      \"pmids\": [\"27060339\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No physiological substrate of PF3D7_1115900 identified in vivo\",\n        \"Redundancy in vitro leaves the enzyme's unique substrate specificity unresolved\",\n        \"Single lab, single method\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The cellular role of PF3D7_1115900 was defined by asking where it acts and which life-cycle stage requires it, revealing a dispensable role in asexual growth but a requirement for efficient gametocytogenesis.\",\n      \"evidence\": \"Endogenous tagging for organellar localization plus gene disruption with blood-stage growth and gametocyte formation readouts in P. falciparum schizonts\",\n      \"pmids\": [\"27060339\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular mechanism linking PF3D7_1115900 activity to gametocyte formation is unresolved\",\n        \"The specific organelles it localizes to are not molecularly identified\",\n        \"Substrates palmitoylated during gametocytogenesis are unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether DHHC9 acts alone or shares function with a sibling enzyme was tested genetically, showing functional overlap with DHHC3 in gliding motility-related processes in a rodent malaria model.\",\n      \"evidence\": \"Double knockout of DHHC3 and DHHC9 compared to single knockouts with in vivo phenotypic analysis in P. berghei\",\n      \"pmids\": [\"27084458\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Genetic epistasis via double knockout in a single study; the specific molecular contribution of DHHC9 is not resolved\",\n        \"No substrate underlying the gliding motility phenotype identified\",\n        \"Relationship between the P. berghei motility role and the P. falciparum gametocyte role is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological substrates of PF3D7_1115900 and the mechanism by which its palmitoyl-transferase activity drives gametocytogenesis remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vivo substrate identified for PF3D7_1115900\",\n        \"Structural basis of catalysis and substrate selection uncharacterized\",\n        \"Mechanistic link between the enzyme and sexual-stage commitment undefined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019706\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016409\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0060470\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"In P. falciparum schizonts, PF3D7_1115900 localizes to distinct (molecularly unidentified) organelles [#0].\",\n      \"PF3D7_1115900 disruption does not affect asexual blood-stage growth but significantly reduces gametocyte formation [#0].\",\n      \"Multiple DHHC enzymes can palmitoylate the same substrate as PF3D7_1115900 in vitro, indicating functional redundancy [#1].\",\n      \"In P. berghei, the DHHC9 ortholog shows functional overlap with DHHC3 in gliding motility-related processes, evidenced by an enhanced double-knockout phenotype [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1115900","name":null,"product":"palmitoyltransferase DHHC9","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0932100","name":null,"product":"palmitoyltransferase DHHC9","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0913600","name":null,"product":"palmitoyltransferase DHHC9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DHHC9","evaluation":null}