{"gene":"TG_252200","gene_symbol":"DHHC7","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2013,"finding":"TgDHHC7 is a palmitoyl acyltransferase (PAT) that localizes to the rhoptries in Toxoplasma gondii; conditional knockdown causes dispersed rhoptries that fail to organize at the apical end, resulting in a complete block in host cell invasion but no defect in attachment or egress, establishing that apical rhoptry tethering is required for invasion but not egress.","method":"Conditional knockdown (TetO-based), subcellular localization imaging, invasion and egress assays","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with specific cellular phenotype (invasion block), multiple orthogonal readouts (localization, invasion, egress), replicated by independent lab in same year","pmids":["23408890"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"A point mutation in the predicted catalytic residue of TgDHHC7 (within the DHHC motif) fails to rescue apical rhoptry tethering, demonstrating that palmitoylation enzymatic activity is required for this function.","method":"Active-site point mutagenesis with complementation rescue assay","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site mutagenesis with functional rescue assay in a single lab, clear causal link between catalytic activity and phenotype","pmids":["23408890"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"TgDHHC7 rhoptry targeting requires a short, highly conserved C-terminal region; the large divergent N-terminal domain is dispensable for both targeting and function.","method":"Domain deletion/truncation analysis with localization imaging","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — truncation mapping with localization readout, single lab","pmids":["23408890"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"TgDHHC7 acts upstream of the palmitoylated armadillo repeat protein TgARO: conditional knockdown of TgDHHC7 mislocalizes TgARO, and independent knockdown of TgARO recapitulates the dispersed rhoptry phenotype, placing TgDHHC7 and TgARO in the same pathway for apical rhoptry tethering.","method":"Conditional knockdown of TgDHHC7 with localization analysis of TgARO; independent conditional knockdown of TgARO with phenotypic comparison","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis via two independent knockdowns with matching phenotypes, replicated by independent lab (PMID 23638681)","pmids":["23408890","23638681"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"DHHC7 localizes to rhoptry organelles across multiple apicomplexan parasites tested, including Plasmodium falciparum, indicating conserved rhoptry targeting of this PAT across the phylum.","method":"Subcellular localization imaging (fluorescence microscopy) in multiple apicomplexan species","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment in multiple organisms, single lab, no functional validation in P. falciparum","pmids":["23638681"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]}],"current_model":"TgDHHC7 is a rhoptry-localized palmitoyl acyltransferase whose catalytic activity is required to palmitoylate and correctly localize the armadillo-repeat protein TgARO, thereby tethering rhoptries at the parasite apex and enabling host cell invasion, while being dispensable for parasite attachment and egress."},"narrative":{"mechanistic_narrative":"TgDHHC7 is a rhoptry-localized palmitoyl acyltransferase (PAT) in Toxoplasma gondii that anchors the secretory rhoptry organelles at the parasite apex to enable host cell invasion [PMID:23408890]. Its enzymatic function depends on an intact DHHC catalytic motif, as active-site point mutation abolishes rescue of apical rhoptry tethering [PMID:23408890]. TgDHHC7 acts upstream of the palmitoylated armadillo-repeat protein TgARO: knockdown of the PAT mislocalizes TgARO, and independent TgARO depletion phenocopies the dispersed-rhoptry defect, placing the two in a single tethering pathway [PMID:23408890, PMID:23638681]. Loss of TgDHHC7 activity disperses rhoptries and produces a complete block in invasion while leaving attachment and egress intact, establishing apical rhoptry positioning as specifically required for invasion [PMID:23408890]. Rhoptry targeting of the enzyme depends on a short conserved C-terminal region rather than its divergent N-terminal domain [PMID:23408890], and rhoptry localization of DHHC7 is conserved across apicomplexans including Plasmodium falciparum [PMID:23638681].","teleology":[{"year":2013,"claim":"Whether a specific palmitoyl acyltransferase controls rhoptry organization was unknown; identifying TgDHHC7 as a rhoptry PAT whose loss disperses rhoptries and blocks invasion established apical rhoptry tethering as an invasion-specific requirement.","evidence":"TetO conditional knockdown with localization imaging plus invasion and egress assays in T. gondii","pmids":["23408890"],"confidence":"High","gaps":["Direct enzymatic palmitoylation of a defined substrate not biochemically reconstituted","Mechanism by which tethering promotes invasion but not egress unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Whether the tethering role required catalytic activity versus a structural scaffold role was unresolved; DHHC-motif point mutation failing to rescue tethering established that enzymatic palmitoylation activity is required.","evidence":"Active-site point mutagenesis with complementation rescue in T. gondii","pmids":["23408890"],"confidence":"High","gaps":["Palmitoylated residue on the substrate not mapped","In vitro acyltransferase activity not demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"The determinants of enzyme targeting were unknown; truncation mapping showed a short conserved C-terminal region directs rhoptry localization while the divergent N-terminus is dispensable.","evidence":"Domain deletion/truncation analysis with localization imaging in T. gondii","pmids":["23408890"],"confidence":"Medium","gaps":["Trafficking machinery recognizing the C-terminal region not identified","Single-lab truncation mapping"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"The relevant substrate pathway was undefined; epistasis showed TgDHHC7 acts upstream of the armadillo-repeat protein TgARO, with TgARO knockdown recapitulating the dispersed-rhoptry phenotype.","evidence":"Paired conditional knockdowns of TgDHHC7 and TgARO with matching phenotypic and localization readouts in T. gondii","pmids":["23408890","23638681"],"confidence":"High","gaps":["Direct enzyme-substrate palmitoylation of TgARO not shown biochemically","Downstream effectors linking TgARO to rhoptry tethering unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Whether rhoptry targeting of this PAT is a general apicomplexan feature was untested; localization across multiple species showed DHHC7 targets rhoptries in Plasmodium falciparum and other apicomplexans.","evidence":"Fluorescence localization imaging in multiple apicomplexan species","pmids":["23638681"],"confidence":"Medium","gaps":["No functional validation in P. falciparum","Whether the Plasmodium ortholog palmitoylates an ARO-equivalent substrate not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Direct biochemical demonstration of TgDHHC7-mediated palmitoylation of TgARO and the molecular link between rhoptry tethering and invasion remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in vitro acyltransferase assay with defined substrate","No structural model of the enzyme or its targeting region","Mechanism connecting apical rhoptry position to invasion competence unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGARO (ARMADILLO REPEAT PROTEIN, PALMITOYLATION SUBSTRATE ACTING DOWNSTREAM OF TGDHHC7)"],"other_free_text":["Catalytic activity of the DHHC motif is required for apical rhoptry tethering; active-site mutation abolishes rescue [#1].","Rhoptry targeting depends on a short conserved C-terminal region; the divergent N-terminal domain is dispensable [#2].","Loss of function disperses rhoptries and blocks host cell invasion without affecting attachment or egress [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23408890","id":"PMC_23408890","title":"A Toxoplasma palmitoyl acyl transferase and the palmitoylated armadillo repeat protein TgARO govern apical rhoptry tethering and reveal a critical role for the rhoptries in host cell invasion but not egress.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/23408890","citation_count":68,"is_preprint":false},{"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3589,"output_tokens":1295,"usd":0.015096,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6308,"output_tokens":2488,"usd":0.04687,"stage2_stop_reason":"end_turn"},"total_usd":0.061966,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"TgDHHC7 is a palmitoyl acyltransferase (PAT) that localizes to the rhoptries in Toxoplasma gondii; conditional knockdown causes dispersed rhoptries that fail to organize at the apical end, resulting in a complete block in host cell invasion but no defect in attachment or egress, establishing that apical rhoptry tethering is required for invasion but not egress.\",\n      \"method\": \"Conditional knockdown (TetO-based), subcellular localization imaging, invasion and egress assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with specific cellular phenotype (invasion block), multiple orthogonal readouts (localization, invasion, egress), replicated by independent lab in same year\",\n      \"pmids\": [\"23408890\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A point mutation in the predicted catalytic residue of TgDHHC7 (within the DHHC motif) fails to rescue apical rhoptry tethering, demonstrating that palmitoylation enzymatic activity is required for this function.\",\n      \"method\": \"Active-site point mutagenesis with complementation rescue assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site mutagenesis with functional rescue assay in a single lab, clear causal link between catalytic activity and phenotype\",\n      \"pmids\": [\"23408890\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TgDHHC7 rhoptry targeting requires a short, highly conserved C-terminal region; the large divergent N-terminal domain is dispensable for both targeting and function.\",\n      \"method\": \"Domain deletion/truncation analysis with localization imaging\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — truncation mapping with localization readout, single lab\",\n      \"pmids\": [\"23408890\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TgDHHC7 acts upstream of the palmitoylated armadillo repeat protein TgARO: conditional knockdown of TgDHHC7 mislocalizes TgARO, and independent knockdown of TgARO recapitulates the dispersed rhoptry phenotype, placing TgDHHC7 and TgARO in the same pathway for apical rhoptry tethering.\",\n      \"method\": \"Conditional knockdown of TgDHHC7 with localization analysis of TgARO; independent conditional knockdown of TgARO with phenotypic comparison\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis via two independent knockdowns with matching phenotypes, replicated by independent lab (PMID 23638681)\",\n      \"pmids\": [\"23408890\", \"23638681\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"DHHC7 localizes to rhoptry organelles across multiple apicomplexan parasites tested, including Plasmodium falciparum, indicating conserved rhoptry targeting of this PAT across the phylum.\",\n      \"method\": \"Subcellular localization imaging (fluorescence microscopy) in multiple apicomplexan species\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment in multiple organisms, single lab, no functional validation in P. falciparum\",\n      \"pmids\": [\"23638681\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgDHHC7 is a rhoptry-localized palmitoyl acyltransferase whose catalytic activity is required to palmitoylate and correctly localize the armadillo-repeat protein TgARO, thereby tethering rhoptries at the parasite apex and enabling host cell invasion, while being dispensable for parasite attachment and egress.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgDHHC7 is a rhoptry-localized palmitoyl acyltransferase (PAT) in Toxoplasma gondii that anchors the secretory rhoptry organelles at the parasite apex to enable host cell invasion [#0]. Its enzymatic function depends on an intact DHHC catalytic motif, as active-site point mutation abolishes rescue of apical rhoptry tethering [#1]. TgDHHC7 acts upstream of the palmitoylated armadillo-repeat protein TgARO: knockdown of the PAT mislocalizes TgARO, and independent TgARO depletion phenocopies the dispersed-rhoptry defect, placing the two in a single tethering pathway [#3]. Loss of TgDHHC7 activity disperses rhoptries and produces a complete block in invasion while leaving attachment and egress intact, establishing apical rhoptry positioning as specifically required for invasion [#0]. Rhoptry targeting of the enzyme depends on a short conserved C-terminal region rather than its divergent N-terminal domain [#2], and rhoptry localization of DHHC7 is conserved across apicomplexans including Plasmodium falciparum [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether a specific palmitoyl acyltransferase controls rhoptry organization was unknown; identifying TgDHHC7 as a rhoptry PAT whose loss disperses rhoptries and blocks invasion established apical rhoptry tethering as an invasion-specific requirement.\",\n      \"evidence\": \"TetO conditional knockdown with localization imaging plus invasion and egress assays in T. gondii\",\n      \"pmids\": [\"23408890\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct enzymatic palmitoylation of a defined substrate not biochemically reconstituted\", \"Mechanism by which tethering promotes invasion but not egress unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether the tethering role required catalytic activity versus a structural scaffold role was unresolved; DHHC-motif point mutation failing to rescue tethering established that enzymatic palmitoylation activity is required.\",\n      \"evidence\": \"Active-site point mutagenesis with complementation rescue in T. gondii\",\n      \"pmids\": [\"23408890\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Palmitoylated residue on the substrate not mapped\", \"In vitro acyltransferase activity not demonstrated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"The determinants of enzyme targeting were unknown; truncation mapping showed a short conserved C-terminal region directs rhoptry localization while the divergent N-terminus is dispensable.\",\n      \"evidence\": \"Domain deletion/truncation analysis with localization imaging in T. gondii\",\n      \"pmids\": [\"23408890\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Trafficking machinery recognizing the C-terminal region not identified\", \"Single-lab truncation mapping\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"The relevant substrate pathway was undefined; epistasis showed TgDHHC7 acts upstream of the armadillo-repeat protein TgARO, with TgARO knockdown recapitulating the dispersed-rhoptry phenotype.\",\n      \"evidence\": \"Paired conditional knockdowns of TgDHHC7 and TgARO with matching phenotypic and localization readouts in T. gondii\",\n      \"pmids\": [\"23408890\", \"23638681\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct enzyme-substrate palmitoylation of TgARO not shown biochemically\", \"Downstream effectors linking TgARO to rhoptry tethering unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether rhoptry targeting of this PAT is a general apicomplexan feature was untested; localization across multiple species showed DHHC7 targets rhoptries in Plasmodium falciparum and other apicomplexans.\",\n      \"evidence\": \"Fluorescence localization imaging in multiple apicomplexan species\",\n      \"pmids\": [\"23638681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional validation in P. falciparum\", \"Whether the Plasmodium ortholog palmitoylates an ARO-equivalent substrate not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Direct biochemical demonstration of TgDHHC7-mediated palmitoylation of TgARO and the molecular link between rhoptry tethering and invasion remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro acyltransferase assay with defined substrate\", \"No structural model of the enzyme or its targeting region\", \"Mechanism connecting apical rhoptry position to invasion competence unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019706\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 2, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgARO (armadillo repeat protein, palmitoylation substrate acting downstream of TgDHHC7)\"],\n    \"other_free_text\": [\n      \"Catalytic activity of the DHHC motif is required for apical rhoptry tethering; active-site mutation abolishes rescue [#1].\",\n      \"Rhoptry targeting depends on a short conserved C-terminal region; the divergent N-terminal domain is dispensable [#2].\",\n      \"Loss of function disperses rhoptries and blocks host cell invasion without affecting attachment or egress [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_252200","name":"DHHC7","product":"palmitoyltransferase DHHC7","uniprot_acc":"A0A125YM35","chromosome":"TGME49_chrIII","start_pos":387364},{"strain":"GT1","gene_id":"TGGT1_252200","name":null,"product":"cell cycle regulator with zn-finger domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrIII","start_pos":370525},{"strain":"RH88","gene_id":"TGRH88_005650","name":null,"product":"cell cycle regulator with zn-finger domain-containing protein","uniprot_acc":null,"chromosome":"CM023084","start_pos":2219533},{"strain":"VEG","gene_id":"TGVEG_252200","name":null,"product":"cell cycle regulator with zn-finger domain-containing protein","uniprot_acc":"A0A0F7UUQ2","chromosome":"TGVEG_chrIII","start_pos":391569}]}