{"gene":"TG_216080","gene_symbol":"AKMT","run_date":"2026-09-08T11:06:30","timeline":{"discoveries":[{"year":2011,"finding":"AKMT (Apical complex lysine (K) methyltransferase) is a protein lysine methyltransferase that regulates motility activation in Toxoplasma gondii; its depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and severely impairs the lytic cycle.","method":"Genetic depletion (conditional knockdown) with motility, invasion, and egress phenotypic readouts","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean loss-of-function with multiple defined cellular phenotypes (motility, invasion, egress) replicated across experiments in the same study","pmids":["21909263"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2011,"finding":"AKMT rapidly redistributes from the apical complex to the parasite body in response to egress-stimulating signals that increase cytoplasmic [Ca²⁺], indicating that its regulation of motility involves precise temporal control of its subcellular localization.","method":"Live fluorescence imaging of AKMT localization following Ca²⁺-elevating stimuli","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiment with functional consequence (motility regulation), directly tied to environmental signal (Ca²⁺), replicated within the same rigorous study","pmids":["21909263"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"The predicted enzymatic (SET) domain of AKMT alone is a very poor enzyme and cannot complement AKMT function in vivo; the N- and C-terminal domains have distinct impacts on enzyme activity, localization, and in vivo function, demonstrating that multiple domains are required for full AKMT activity.","method":"Systematic truncation mutagenesis with in vitro enzymatic assays and in vivo complementation","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site/domain mutagenesis combined with in vitro enzymatic assay and in vivo complementation, single lab but two orthogonal methods","pmids":["23685344"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"Phylogenetic analyses established that AKMT orthologs form a new, parasite-specific subfamily of lysine methyltransferases (KMTs).","method":"Phylogenetic analysis of AKMT and related KMT sequences","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 4 / Moderate — computational phylogenetic analysis only; no experimental validation of the classification, but finding is consistent across corpus","pmids":["23685344"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"The crystal structure of the conserved C-terminal portion (aa289-709) of T. gondii AKMT was solved at 2.1-Å resolution, revealing that AKMT dimerizes via a unique intermolecular interface formed by a C-terminal tetratricopeptide repeat-like (TPR-like) domain together with a specific zinc-binding motif absent from all other KMTs.","method":"X-ray crystallography at 2.1-Å resolution","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution crystal structure with detailed structural characterization of the dimerization interface and zinc-binding motif","pmids":["30148980"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Disruption of AKMT dimerization impaired both its enzyme activity in vitro and parasite egress from infected host cells in vivo, establishing that dimerization is required for AKMT function.","method":"Structure-guided mutagenesis of the dimerization interface combined with in vitro enzymatic assay and in vivo egress assay","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution/mutagenesis with in vitro enzyme activity plus in vivo functional readout (egress), single lab but multiple orthogonal methods","pmids":["30148980"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Structural comparisons reveal that AKMT is related to SMYD-family KMTs but possesses unique structural features (including the dimerization interface and zinc-binding motif) conserved among apicomplexan parasites and their free-living relatives but absent from animal KMTs, identifying AKMT as the founding member of a new KMT subclass.","method":"Crystal structure comparison with known KMT structures","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — based on high-resolution crystal structure with detailed comparative structural analysis","pmids":["30148980"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"AKMT-mediated methylation controls a flux of F-actin initiated at the conoid by FRM1, which is crucial for motility, invasion, and egress, placing AKMT in a post-translational regulatory pathway alongside PKG and CDPK1 phosphorylation that governs actin polymerization dynamics.","method":"Genetic epistasis using F-actin chromobodies combined with gene disruption of FRM1, myosin A, myosin H, PKG, CDPK1, and AKMT","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — epistasis analysis using multiple gene disruptions with live F-actin imaging, placing AKMT in a defined pathway with functional phenotypic readouts","pmids":["30753127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AKMT is a parasite-specific, dimeric SET-domain lysine methyltransferase that localizes to the apical complex and rapidly redistributes to the parasite body upon Ca²⁺ elevation; its methyltransferase activity—requiring dimerization via a unique TPR-like/zinc-binding interface and contributions from both N- and C-terminal domains—controls a FRM1-nucleated cortical F-actin flux alongside PKG and CDPK1, thereby activating parasite motility, invasion, and egress during the lytic cycle of Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"AKMT (Apical complex lysine methyltransferase) is a parasite-specific SET-domain protein lysine methyltransferase that activates the motile phase of the Toxoplasma gondii lytic cycle, with its depletion severely impairing motility activation, host-cell invasion, and egress [PMID:21909263]. Its regulatory output is timed by subcellular relocation: AKMT normally resides at the apical complex but rapidly redistributes to the parasite body upon egress-stimulating Ca²⁺ elevation, coupling its activity to the signal that triggers motility [PMID:21909263]. Full function requires more than the catalytic SET domain, which alone is a poor enzyme unable to complement in vivo—both N- and C-terminal domains contribute to activity, localization, and function [PMID:23685344]—and depends on homodimerization through a unique C-terminal TPR-like domain and zinc-binding motif; disrupting this interface abolishes both enzymatic activity and egress [PMID:30148980]. Downstream, AKMT-mediated methylation governs a conoid-nucleated flux of F-actin initiated by the formin FRM1, acting alongside PKG and CDPK1 phosphorylation to control actin polymerization dynamics that drive motility, invasion, and egress [PMID:30753127]. The physiological methylation substrate(s) of AKMT have not been identified in the available corpus.","teleology":[{"year":2011,"claim":"Established AKMT as a lysine methyltransferase essential for switching on parasite motility, defining its place at the top of the lytic-cycle motility program rather than as a general chromatin enzyme.","evidence":"Conditional knockdown with motility, invasion, and egress phenotypic readouts in T. gondii","pmids":["21909263"],"confidence":"High","gaps":["No methylation substrate identified","Molecular link between methylation and the motility machinery not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2011,"claim":"Showed that AKMT function is regulated spatially and temporally—its Ca²⁺-triggered redistribution from apical complex to parasite body ties enzyme deployment to the egress signal.","evidence":"Live fluorescence imaging of AKMT localization following Ca²⁺-elevating stimuli","pmids":["21909263"],"confidence":"High","gaps":["Mechanism sensing Ca²⁺ and driving relocation unknown","Whether relocation changes catalytic activity or only substrate access not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Demonstrated that the SET domain alone is insufficient and that flanking N- and C-terminal domains are required for activity and in vivo complementation, reframing AKMT as a multidomain enzyme.","evidence":"Truncation mutagenesis with in vitro enzymatic assays and in vivo complementation in T. gondii","pmids":["23685344"],"confidence":"High","gaps":["Specific molecular contribution of each domain not resolved","Substrate binding determinants not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Placed AKMT phylogenetically as the founding member of a new parasite-specific KMT subfamily, indicating a distinct evolutionary origin from host enzymes.","evidence":"Phylogenetic analysis of AKMT and related KMT sequences","pmids":["23685344"],"confidence":"Medium","gaps":["Computational only; no experimental validation of the classification","Functional conservation across the subfamily untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Solved the C-terminal crystal structure and revealed dimerization via a unique TPR-like/zinc-binding interface, explaining the multidomain activity requirement and defining a new KMT subclass related to SMYD enzymes.","evidence":"X-ray crystallography of AKMT aa289-709 at 2.1 Å with comparative structural analysis; structure-guided mutagenesis with in vitro enzyme and in vivo egress assays","pmids":["30148980"],"confidence":"High","gaps":["Structure of full-length protein including N-terminal region not determined","No substrate-bound structure to define catalytic mechanism"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Positioned AKMT in a defined motility-activation pathway, showing its methylation controls FRM1-nucleated conoidal F-actin flux in parallel with PKG and CDPK1 phosphorylation.","evidence":"Genetic epistasis with F-actin chromobodies and disruption of FRM1, myosin A, myosin H, PKG, CDPK1, and AKMT in T. gondii","pmids":["30753127"],"confidence":"High","gaps":["Direct methylation target linking AKMT to F-actin flux not identified","How AKMT integrates with PKG/CDPK1 signaling mechanistically unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The physiological methylation substrate(s) of AKMT and the direct biochemical link between methylation and F-actin dynamics remain to be identified.","evidence":"","pmids":[],"confidence":"High","gaps":["No validated in vivo methylation substrate","Mechanistic connection from methyl-mark to actin polymerization not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["AKMT homodimer (via C-terminal TPR-like/zinc-binding interface)"],"partners":["FRM1 (FUNCTIONAL/EPISTATIC, F-ACTIN NUCLEATION)","PKG (PARALLEL MOTILITY-ACTIVATION PATHWAY)","CDPK1 (PARALLEL MOTILITY-ACTIVATION PATHWAY)"],"other_free_text":["Ca²⁺-triggered relocation from apical complex to parasite body couples AKMT deployment to the egress signal [#1].","Founding member of a parasite-specific KMT subclass related to SMYD-family enzymes but bearing a unique dimerization interface and zinc-binding motif absent from animal KMTs [#3, #6].","Catalytic SET domain alone is insufficient; N- and C-terminal domains are required for activity, localization, and in vivo function [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"21909263","id":"PMC_21909263","title":"The motility of a human parasite, Toxoplasma gondii, is regulated by a novel lysine methyltransferase.","date":"2011","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/21909263","citation_count":72,"is_preprint":false},{"pmid":"30753127","id":"PMC_30753127","title":"Three F-actin assembly centers regulate organelle inheritance, cell-cell communication and motility in Toxoplasma gondii.","date":"2019","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/30753127","citation_count":68,"is_preprint":false},{"pmid":"23685344","id":"PMC_23685344","title":"Identification of functional modules of AKMT, a novel lysine methyltransferase regulating the motility of Toxoplasma gondii.","date":"2013","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/23685344","citation_count":14,"is_preprint":false},{"pmid":"30148980","id":"PMC_30148980","title":"Structure of a Novel Dimeric SET Domain Methyltransferase that Regulates Cell Motility.","date":"2018","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30148980","citation_count":5,"is_preprint":false},{"pmid":"27697019","id":"PMC_27697019","title":"Identification, production and assessment of two Toxoplasma gondii recombinant proteins for use in a Toxoplasma IgG avidity assay.","date":"2016","source":"Pathogens and global health","url":"https://pubmed.ncbi.nlm.nih.gov/27697019","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4657,"output_tokens":1976,"usd":0.021805,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7382,"output_tokens":2893,"usd":0.054617,"stage2_stop_reason":"end_turn"},"total_usd":0.076422,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"AKMT (Apical complex lysine (K) methyltransferase) is a protein lysine methyltransferase that regulates motility activation in Toxoplasma gondii; its depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and severely impairs the lytic cycle.\",\n      \"method\": \"Genetic depletion (conditional knockdown) with motility, invasion, and egress phenotypic readouts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean loss-of-function with multiple defined cellular phenotypes (motility, invasion, egress) replicated across experiments in the same study\",\n      \"pmids\": [\"21909263\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"AKMT rapidly redistributes from the apical complex to the parasite body in response to egress-stimulating signals that increase cytoplasmic [Ca²⁺], indicating that its regulation of motility involves precise temporal control of its subcellular localization.\",\n      \"method\": \"Live fluorescence imaging of AKMT localization following Ca²⁺-elevating stimuli\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiment with functional consequence (motility regulation), directly tied to environmental signal (Ca²⁺), replicated within the same rigorous study\",\n      \"pmids\": [\"21909263\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The predicted enzymatic (SET) domain of AKMT alone is a very poor enzyme and cannot complement AKMT function in vivo; the N- and C-terminal domains have distinct impacts on enzyme activity, localization, and in vivo function, demonstrating that multiple domains are required for full AKMT activity.\",\n      \"method\": \"Systematic truncation mutagenesis with in vitro enzymatic assays and in vivo complementation\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site/domain mutagenesis combined with in vitro enzymatic assay and in vivo complementation, single lab but two orthogonal methods\",\n      \"pmids\": [\"23685344\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Phylogenetic analyses established that AKMT orthologs form a new, parasite-specific subfamily of lysine methyltransferases (KMTs).\",\n      \"method\": \"Phylogenetic analysis of AKMT and related KMT sequences\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — computational phylogenetic analysis only; no experimental validation of the classification, but finding is consistent across corpus\",\n      \"pmids\": [\"23685344\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The crystal structure of the conserved C-terminal portion (aa289-709) of T. gondii AKMT was solved at 2.1-Å resolution, revealing that AKMT dimerizes via a unique intermolecular interface formed by a C-terminal tetratricopeptide repeat-like (TPR-like) domain together with a specific zinc-binding motif absent from all other KMTs.\",\n      \"method\": \"X-ray crystallography at 2.1-Å resolution\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution crystal structure with detailed structural characterization of the dimerization interface and zinc-binding motif\",\n      \"pmids\": [\"30148980\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Disruption of AKMT dimerization impaired both its enzyme activity in vitro and parasite egress from infected host cells in vivo, establishing that dimerization is required for AKMT function.\",\n      \"method\": \"Structure-guided mutagenesis of the dimerization interface combined with in vitro enzymatic assay and in vivo egress assay\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution/mutagenesis with in vitro enzyme activity plus in vivo functional readout (egress), single lab but multiple orthogonal methods\",\n      \"pmids\": [\"30148980\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Structural comparisons reveal that AKMT is related to SMYD-family KMTs but possesses unique structural features (including the dimerization interface and zinc-binding motif) conserved among apicomplexan parasites and their free-living relatives but absent from animal KMTs, identifying AKMT as the founding member of a new KMT subclass.\",\n      \"method\": \"Crystal structure comparison with known KMT structures\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — based on high-resolution crystal structure with detailed comparative structural analysis\",\n      \"pmids\": [\"30148980\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"AKMT-mediated methylation controls a flux of F-actin initiated at the conoid by FRM1, which is crucial for motility, invasion, and egress, placing AKMT in a post-translational regulatory pathway alongside PKG and CDPK1 phosphorylation that governs actin polymerization dynamics.\",\n      \"method\": \"Genetic epistasis using F-actin chromobodies combined with gene disruption of FRM1, myosin A, myosin H, PKG, CDPK1, and AKMT\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — epistasis analysis using multiple gene disruptions with live F-actin imaging, placing AKMT in a defined pathway with functional phenotypic readouts\",\n      \"pmids\": [\"30753127\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"AKMT is a parasite-specific, dimeric SET-domain lysine methyltransferase that localizes to the apical complex and rapidly redistributes to the parasite body upon Ca²⁺ elevation; its methyltransferase activity—requiring dimerization via a unique TPR-like/zinc-binding interface and contributions from both N- and C-terminal domains—controls a FRM1-nucleated cortical F-actin flux alongside PKG and CDPK1, thereby activating parasite motility, invasion, and egress during the lytic cycle of Toxoplasma gondii.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AKMT (Apical complex lysine methyltransferase) is a parasite-specific SET-domain protein lysine methyltransferase that activates the motile phase of the Toxoplasma gondii lytic cycle, with its depletion severely impairing motility activation, host-cell invasion, and egress [#0]. Its regulatory output is timed by subcellular relocation: AKMT normally resides at the apical complex but rapidly redistributes to the parasite body upon egress-stimulating Ca²⁺ elevation, coupling its activity to the signal that triggers motility [#1]. Full function requires more than the catalytic SET domain, which alone is a poor enzyme unable to complement in vivo—both N- and C-terminal domains contribute to activity, localization, and function [#2]—and depends on homodimerization through a unique C-terminal TPR-like domain and zinc-binding motif; disrupting this interface abolishes both enzymatic activity and egress [#4, #5]. Downstream, AKMT-mediated methylation governs a conoid-nucleated flux of F-actin initiated by the formin FRM1, acting alongside PKG and CDPK1 phosphorylation to control actin polymerization dynamics that drive motility, invasion, and egress [#7]. The physiological methylation substrate(s) of AKMT have not been identified in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established AKMT as a lysine methyltransferase essential for switching on parasite motility, defining its place at the top of the lytic-cycle motility program rather than as a general chromatin enzyme.\",\n      \"evidence\": \"Conditional knockdown with motility, invasion, and egress phenotypic readouts in T. gondii\",\n      \"pmids\": [\"21909263\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No methylation substrate identified\", \"Molecular link between methylation and the motility machinery not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed that AKMT function is regulated spatially and temporally—its Ca²⁺-triggered redistribution from apical complex to parasite body ties enzyme deployment to the egress signal.\",\n      \"evidence\": \"Live fluorescence imaging of AKMT localization following Ca²⁺-elevating stimuli\",\n      \"pmids\": [\"21909263\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism sensing Ca²⁺ and driving relocation unknown\", \"Whether relocation changes catalytic activity or only substrate access not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrated that the SET domain alone is insufficient and that flanking N- and C-terminal domains are required for activity and in vivo complementation, reframing AKMT as a multidomain enzyme.\",\n      \"evidence\": \"Truncation mutagenesis with in vitro enzymatic assays and in vivo complementation in T. gondii\",\n      \"pmids\": [\"23685344\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific molecular contribution of each domain not resolved\", \"Substrate binding determinants not mapped\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed AKMT phylogenetically as the founding member of a new parasite-specific KMT subfamily, indicating a distinct evolutionary origin from host enzymes.\",\n      \"evidence\": \"Phylogenetic analysis of AKMT and related KMT sequences\",\n      \"pmids\": [\"23685344\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Computational only; no experimental validation of the classification\", \"Functional conservation across the subfamily untested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Solved the C-terminal crystal structure and revealed dimerization via a unique TPR-like/zinc-binding interface, explaining the multidomain activity requirement and defining a new KMT subclass related to SMYD enzymes.\",\n      \"evidence\": \"X-ray crystallography of AKMT aa289-709 at 2.1 Å with comparative structural analysis; structure-guided mutagenesis with in vitro enzyme and in vivo egress assays\",\n      \"pmids\": [\"30148980\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of full-length protein including N-terminal region not determined\", \"No substrate-bound structure to define catalytic mechanism\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Positioned AKMT in a defined motility-activation pathway, showing its methylation controls FRM1-nucleated conoidal F-actin flux in parallel with PKG and CDPK1 phosphorylation.\",\n      \"evidence\": \"Genetic epistasis with F-actin chromobodies and disruption of FRM1, myosin A, myosin H, PKG, CDPK1, and AKMT in T. gondii\",\n      \"pmids\": [\"30753127\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct methylation target linking AKMT to F-actin flux not identified\", \"How AKMT integrates with PKG/CDPK1 signaling mechanistically unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological methylation substrate(s) of AKMT and the direct biochemical link between methylation and F-actin dynamics remain to be identified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No validated in vivo methylation substrate\", \"Mechanistic connection from methyl-mark to actin polymerization not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016279\", \"supporting_discovery_ids\": [0, 2, 5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [4, 5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020007\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071827\", \"supporting_discovery_ids\": [7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006935\", \"supporting_discovery_ids\": [0, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"AKMT homodimer (via C-terminal TPR-like/zinc-binding interface)\"],\n    \"partners\": [\"FRM1 (functional/epistatic, F-actin nucleation)\", \"PKG (parallel motility-activation pathway)\", \"CDPK1 (parallel motility-activation pathway)\"],\n    \"other_free_text\": [\n      \"Ca²⁺-triggered relocation from apical complex to parasite body couples AKMT deployment to the egress signal [#1].\",\n      \"Founding member of a parasite-specific KMT subclass related to SMYD-family enzymes but bearing a unique dimerization interface and zinc-binding motif absent from animal KMTs [#3, #6].\",\n      \"Catalytic SET domain alone is insufficient; N- and C-terminal domains are required for activity, localization, and in vivo function [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_216080","name":"AKMT","product":"apical complex lysine methyltransferase","uniprot_acc":"A0A125YQK8","chromosome":"TGME49_chrXI","start_pos":6401719},{"strain":"GT1","gene_id":"TGGT1_216080","name":null,"product":"apical complex lysine methyltransferase","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":6322234},{"strain":"RH88","gene_id":"TGRH88_056480","name":null,"product":"apical complex lysine methyltransferase","uniprot_acc":null,"chromosome":"CM023092","start_pos":6461293},{"strain":"VEG","gene_id":"TGVEG_216080","name":null,"product":"apical complex lysine methyltransferase","uniprot_acc":"B9Q0K5","chromosome":"TGVEG_chrXI","start_pos":6396625}]}