{"gene":"TG_278850","gene_symbol":"DHHC2","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2020,"finding":"TgDHHC2 is an IMC-resident palmitoyl acyltransferase essential for T. gondii tachyzoite survival; its disruption causes rapid collapse of the inner membrane complex (IMC) in developing daughter cells, leading to dramatic morphological defects, while other organelles are affected in localization but not biogenesis.","method":"Conditional knockdown/disruption of TgDHHC2 with phenotypic readout (IMC collapse, morphological defects by imaging)","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic disruption with defined cellular phenotype, IMC localization confirmed, supported by functional substrate identification in same study","pmids":["32329212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgDHHC2 localizes to the inner membrane complex (IMC) of T. gondii, and its acyl-transferase activity is involved sequentially with TgDHHC14 in formation of IMC sub-compartments, acting at an earlier step.","method":"Fluorescence localization and conditional depletion with sequential functional analysis","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct subcellular localization experiment combined with loss-of-function showing specific pathway position relative to TgDHHC14","pmids":["32329212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgISP1, TgISP3, TgIAP1, and TgIAP2 lose their membrane association upon TgDHHC2 depletion, identifying them as likely palmitoylation substrates of TgDHHC2.","method":"Fractionation/localization of known palmitoylated IMC proteins after conditional depletion of TgDHHC2","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, indirect substrate inference from membrane association loss upon depletion, no direct acylation assay performed","pmids":["32329212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgDHHC2 is an IMC-resident palmitoyl S-acyl transferase that is essential for T. gondii tachyzoite survival; it acts sequentially with TgDHHC14 to build distinct sub-compartments of the inner membrane complex, and its catalytic activity is required to maintain membrane association of IMC proteins TgISP1/3 and TgIAP1/2, which are its likely palmitoylation substrates."},"narrative":{"mechanistic_narrative":"TgDHHC2 is an inner membrane complex (IMC)-resident palmitoyl S-acyltransferase essential for Toxoplasma gondii tachyzoite survival [PMID:32329212]. Conditional disruption causes rapid collapse of the IMC in developing daughter cells and severe morphological defects, while other organelles are mislocalized but still form [PMID:32329212]. TgDHHC2 acts sequentially with TgDHHC14 in the construction of distinct IMC sub-compartments, functioning at an earlier step [PMID:32329212]. Its catalytic activity maintains the membrane association of the palmitoylated IMC proteins TgISP1, TgISP3, TgIAP1, and TgIAP2, identifying these as its likely palmitoylation substrates [PMID:32329212]. Direct acylation of these candidate substrates has not been demonstrated in the available corpus.","teleology":[{"year":2020,"claim":"Defining where TgDHHC2 acts and what fails without it established that it is an IMC-resident acyltransferase whose loss collapses the IMC during daughter cell formation, distinguishing a biogenesis role from mere protein mislocalization.","evidence":"Fluorescence localization and conditional depletion of TgDHHC2 with imaging of IMC and organelle phenotypes","pmids":["32329212"],"confidence":"High","gaps":["Direct enzymatic acyltransferase activity not biochemically assayed","How IMC collapse causes death not mechanistically dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Placing TgDHHC2 relative to TgDHHC14 answered whether IMC sub-compartments are built by a single enzyme or a pathway; the two enzymes act sequentially with TgDHHC2 at an earlier step.","evidence":"Conditional depletion with sequential functional analysis of IMC sub-compartment formation","pmids":["32329212"],"confidence":"High","gaps":["Molecular basis of the ordering between DHHC2 and DHHC14 unknown","Whether the two enzymes act on overlapping or distinct substrate sets not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Identifying which proteins depend on TgDHHC2 addressed its substrate range; loss of membrane association of TgISP1, TgISP3, TgIAP1, and TgIAP2 upon depletion implicated them as its palmitoylation targets.","evidence":"Fractionation/localization of known palmitoylated IMC proteins after conditional depletion of TgDHHC2","pmids":["32329212"],"confidence":"Medium","gaps":["Substrate inference is indirect — no direct acylation assay performed on the candidate substrates","Loss of membrane association could be an indirect consequence of IMC collapse","Single lab, not independently confirmed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGDHHC14 (ACTS SEQUENTIALLY IN IMC SUB-COMPARTMENT FORMATION)","TGISP1 (LIKELY SUBSTRATE)","TGISP3 (LIKELY SUBSTRATE)","TGIAP1 (LIKELY SUBSTRATE)","TGIAP2 (LIKELY SUBSTRATE)"],"other_free_text":["Essential for T. gondii tachyzoite survival; disruption collapses the IMC in developing daughter cells.","Member of the apicomplexan-specific DHHC enzymes that, unlike other eukaryotic DHHCs, lack functional redundancy."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"32329212","id":"PMC_32329212","title":"Two palmitoyl acyltransferases involved sequentially in the biogenesis of the inner membrane complex of Toxoplasma gondii.","date":"2020","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32329212","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4001,"output_tokens":1072,"usd":0.014042,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5974,"output_tokens":2253,"usd":0.043097,"stage2_stop_reason":"end_turn"},"total_usd":0.060072,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"summary amended"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"TgDHHC2 is an IMC-resident palmitoyl acyltransferase essential for T. gondii tachyzoite survival; its disruption causes rapid collapse of the inner membrane complex (IMC) in developing daughter cells, leading to dramatic morphological defects, while other organelles are affected in localization but not biogenesis.\",\n      \"method\": \"Conditional knockdown/disruption of TgDHHC2 with phenotypic readout (IMC collapse, morphological defects by imaging)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic disruption with defined cellular phenotype, IMC localization confirmed, supported by functional substrate identification in same study\",\n      \"pmids\": [\"32329212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgDHHC2 localizes to the inner membrane complex (IMC) of T. gondii, and its acyl-transferase activity is involved sequentially with TgDHHC14 in formation of IMC sub-compartments, acting at an earlier step.\",\n      \"method\": \"Fluorescence localization and conditional depletion with sequential functional analysis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular localization experiment combined with loss-of-function showing specific pathway position relative to TgDHHC14\",\n      \"pmids\": [\"32329212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgISP1, TgISP3, TgIAP1, and TgIAP2 lose their membrane association upon TgDHHC2 depletion, identifying them as likely palmitoylation substrates of TgDHHC2.\",\n      \"method\": \"Fractionation/localization of known palmitoylated IMC proteins after conditional depletion of TgDHHC2\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, indirect substrate inference from membrane association loss upon depletion, no direct acylation assay performed\",\n      \"pmids\": [\"32329212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TgDHHC2 is essential for T. gondii tachyzoite growth, as part of a global analysis showing that unlike other eukaryotes, several apicomplexan-specific DHHCs including TgDHHC2 lack functional redundancy and are required for parasite survival.\",\n      \"method\": \"Comprehensive DHHC family essentiality screen in T. gondii (knockout/disruption attempts with growth phenotype assessment)\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic screen across DHHC family, essentiality confirmed by failed disruption/conditional depletion, replicated across multiple DHHCs in same study\",\n      \"pmids\": [\"23638681\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgDHHC2 is an IMC-resident palmitoyl S-acyl transferase that is essential for T. gondii tachyzoite survival; it acts sequentially with TgDHHC14 to build distinct sub-compartments of the inner membrane complex, and its catalytic activity is required to maintain membrane association of IMC proteins TgISP1/3 and TgIAP1/2, which are its likely palmitoylation substrates.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgDHHC2 is an inner membrane complex (IMC)-resident palmitoyl S-acyltransferase essential for Toxoplasma gondii tachyzoite survival [#0, #3]. Conditional disruption causes rapid collapse of the IMC in developing daughter cells and severe morphological defects, while other organelles are mislocalized but still form [#0]. TgDHHC2 acts sequentially with TgDHHC14 in the construction of distinct IMC sub-compartments, functioning at an earlier step [#1]. Its catalytic activity maintains the membrane association of the palmitoylated IMC proteins TgISP1, TgISP3, TgIAP1, and TgIAP2, identifying these as its likely palmitoylation substrates [#2]. Direct acylation of these candidate substrates has not been demonstrated in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether apicomplexan DHHC enzymes are individually dispensable answered whether TgDHHC2 could be a survival factor; unlike the redundant DHHC families of other eukaryotes, TgDHHC2 proved to be non-redundant and required for parasite growth.\",\n      \"evidence\": \"Comprehensive DHHC family essentiality screen in T. gondii using disruption/depletion with growth readout\",\n      \"pmids\": [\"23638681\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Screen established essentiality but did not define the cellular process or substrates\",\n        \"No localization assigned in this study\",\n        \"Mechanism of the growth defect unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defining where TgDHHC2 acts and what fails without it established that it is an IMC-resident acyltransferase whose loss collapses the IMC during daughter cell formation, distinguishing a biogenesis role from mere protein mislocalization.\",\n      \"evidence\": \"Fluorescence localization and conditional depletion of TgDHHC2 with imaging of IMC and organelle phenotypes\",\n      \"pmids\": [\"32329212\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Direct enzymatic acyltransferase activity not biochemically assayed\",\n        \"How IMC collapse causes death not mechanistically dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing TgDHHC2 relative to TgDHHC14 answered whether IMC sub-compartments are built by a single enzyme or a pathway; the two enzymes act sequentially with TgDHHC2 at an earlier step.\",\n      \"evidence\": \"Conditional depletion with sequential functional analysis of IMC sub-compartment formation\",\n      \"pmids\": [\"32329212\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Molecular basis of the ordering between DHHC2 and DHHC14 unknown\",\n        \"Whether the two enzymes act on overlapping or distinct substrate sets not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying which proteins depend on TgDHHC2 addressed its substrate range; loss of membrane association of TgISP1, TgISP3, TgIAP1, and TgIAP2 upon depletion implicated them as its palmitoylation targets.\",\n      \"evidence\": \"Fractionation/localization of known palmitoylated IMC proteins after conditional depletion of TgDHHC2\",\n      \"pmids\": [\"32329212\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Substrate inference is indirect \\u2014 no direct acylation assay performed on the candidate substrates\",\n        \"Loss of membrane association could be an indirect consequence of IMC collapse\",\n        \"Single lab, not independently confirmed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TgDHHC2 directly palmitoylates TgISP1/3 and TgIAP1/2 and the structural/enzymatic basis of its activity remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct in vitro or in vivo acylation assay linking TgDHHC2 to specific substrate cysteines\",\n        \"No structural model of the enzyme\",\n        \"Mechanism coordinating TgDHHC2 and TgDHHC14 activity undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019706\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031248\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0018345\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TgDHHC14 (acts sequentially in IMC sub-compartment formation)\",\n      \"TgISP1 (likely substrate)\",\n      \"TgISP3 (likely substrate)\",\n      \"TgIAP1 (likely substrate)\",\n      \"TgIAP2 (likely substrate)\"\n    ],\n    \"other_free_text\": [\n      \"Essential for T. gondii tachyzoite survival; disruption collapses the IMC in developing daughter cells.\",\n      \"Member of the apicomplexan-specific DHHC enzymes that, unlike other eukaryotic DHHCs, lack functional redundancy.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_278850","name":"DHHC2","product":"palmitoyltransferase DHHC2","uniprot_acc":"A0A125YWM0","chromosome":"TGME49_chrXII","start_pos":5820378},{"strain":"GT1","gene_id":"TGGT1_278850","name":null,"product":"DHHC zinc finger domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":5737011},{"strain":"RH88","gene_id":"TGRH88_065030","name":null,"product":"DHHC zinc finger domain-containing protein","uniprot_acc":null,"chromosome":"CM023093","start_pos":5900360},{"strain":"VEG","gene_id":"TGVEG_278850","name":null,"product":"DHHC zinc finger domain-containing protein","uniprot_acc":"A0A125YWM5","chromosome":"TGVEG_chrXII","start_pos":5827170}]}