{"gene":"TG_301270","gene_symbol":"TKL1","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2018,"finding":"TgTKL1 localizes to the nucleus in Toxoplasma gondii, as determined by endogenous tagging.","method":"Endogenous tagging / fluorescence localization","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by endogenous tagging, single lab, supported by functional studies in same paper","pmids":["29559568"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2018,"finding":"TgTKL1 contains a plant-like Enhanced Disease Resistance 1 (EDR1) domain, a domain architecture unique to plants and protozoa.","method":"Bioinformatic domain analysis / sequence annotation","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — computational domain prediction, no functional mutagenesis of the domain reported in abstract","pmids":["29559568"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Knockout of TgTKL1 causes specific impairment of host cell attachment, defects in microneme secretion and processing, and failure to progress through the lytic cycle.","method":"Genetic knockout / lytic cycle assay / attachment assay / microneme secretion assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with specific phenotypic readouts (attachment, microneme secretion/processing) and in vivo virulence, multiple orthogonal methods in one study","pmids":["29559568"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2018,"finding":"TgTKL1 knockout parasites show differential expression of over 200 genes, including significant downregulation of multiple genes implicated in host cell attachment and invasion.","method":"Transcriptomics (RNA-seq) on TgTKL1 knockout parasites","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transcriptomics on clean KO, single lab, functional consequence (attachment/invasion) linked","pmids":["29559568"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2018,"finding":"TgTKL1 knockout parasites are completely avirulent in mice infected intraperitoneally, establishing TgTKL1 as essential for acute toxoplasmosis.","method":"Mouse acute infection model with TgTKL1 knockout parasites","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO, in vivo virulence model, all mice survived; consistent with in vitro mechanistic findings","pmids":["29559568"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"finding":"TgTKL1 is a bona fide kinase, confirmed by in vitro kinase activity assay using purified recombinant TgTKL1 protein.","method":"In vitro kinase assay with purified recombinant protein","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro biochemical demonstration of kinase activity with recombinant protein, single lab","pmids":["39475314"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"finding":"A TgTKL1 kinase-dead mutant (generated by CRISPR-Cas9 active-site mutagenesis) displays defects in parasite growth and host cell invasion identical to TgTKL1 knockout, establishing that catalytic kinase activity is required for TgTKL1 function.","method":"CRISPR-Cas9 active-site mutagenesis / kinase mutant strain / growth and invasion assays","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 1 / Strong — active-site mutagenesis with in vitro phenotypic validation (growth, invasion) and in vivo virulence, multiple orthogonal readouts","pmids":["39475314"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"finding":"Loss of TgTKL1 kinase function leads to downregulation of TgSUB1 (subtilisin 1) expression, resulting in defects in post-exocytosis processing of micronemal proteins, an event critical for host cell invasion.","method":"Transcriptomics on kinase mutant + micronemal protein processing assay","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 2 / Strong — mechanistic link from kinase function to transcriptional target (TgSUB1) to micronemal processing defect established by two orthogonal methods in one study","pmids":["39475314"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"finding":"TgTKL1 kinase mutant parasites are completely avirulent in the mouse model of acute toxoplasmosis, confirming that kinase activity underlies the virulence function of TgTKL1.","method":"Mouse acute infection model with TgTKL1 kinase mutant parasites","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean kinase-dead mutant, in vivo virulence model, consistent with knockout data from prior study","pmids":["39475314"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"TgTKL1 is a nuclear, plant-like tyrosine kinase-like (TKL) family kinase in Toxoplasma gondii whose catalytic kinase activity is essential for parasite propagation: it maintains expression of invasion-related genes (including TgSUB1) through a nuclear signaling pathway, thereby enabling proper microneme secretion and post-exocytosis processing of micronemal proteins, host cell attachment, and invasion, and loss of TgTKL1 or its kinase activity renders parasites completely avirulent in mice."},"narrative":{"mechanistic_narrative":"TgTKL1 is a nuclear tyrosine kinase-like family kinase in Toxoplasma gondii whose catalytic activity is essential for the lytic cycle and parasite virulence [PMID:29559568, PMID:39475314]. Localizing to the parasite nucleus [PMID:29559568], TgTKL1 acts as a signaling kinase whose activity sustains a transcriptional program required for host cell attachment and invasion: its loss deregulates over 200 genes, including downregulation of multiple invasion- and attachment-related genes [PMID:29559568]. Mechanistically, kinase function maintains expression of the subtilisin protease TgSUB1, and its loss impairs post-exocytosis processing of micronemal proteins, a step critical for invasion [PMID:39475314]. Consequently, TgTKL1 knockout or active-site kinase-dead parasites fail host cell attachment, show defective microneme secretion and processing, cannot progress through the lytic cycle, and are completely avirulent in mice [PMID:29559568, PMID:39475314]. How TgTKL1 nuclear signaling connects to its downstream transcriptional targets, and the identity of its direct phosphorylation substrates, have not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where TgTKL1 acts and whether it is dispensable answered whether this kinase functions in nuclear signaling and is required for the parasite lytic cycle.","evidence":"Endogenous tagging/fluorescence localization plus genetic knockout with attachment, microneme secretion, and lytic cycle assays in T. gondii RH","pmids":["29559568"],"confidence":"High","gaps":["Direct kinase activity not yet demonstrated at this stage","Mechanism linking nuclear localization to invasion defect unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2018,"claim":"Transcriptomics of the knockout linked TgTKL1 to a gene-expression program, framing it as a nuclear regulator of invasion-related genes rather than a purely structural or secretory factor.","evidence":"RNA-seq on TgTKL1 knockout parasites (T. gondii RH)","pmids":["29559568"],"confidence":"Medium","gaps":["Direct versus indirect transcriptional targets not distinguished","No DNA-binding or transcription-factor partner identified"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2018,"claim":"Complete loss of virulence in mice established TgTKL1 as essential for acute toxoplasmosis in vivo, not merely for in vitro growth.","evidence":"Mouse intraperitoneal acute infection model with knockout parasites (T. gondii RH)","pmids":["29559568"],"confidence":"High","gaps":["Whether virulence loss stems from kinase activity was not tested at this stage"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"claim":"In vitro activity and active-site mutagenesis proved that the catalytic kinase function itself, not merely the protein's presence, drives growth, invasion, and virulence.","evidence":"In vitro kinase assay with purified recombinant protein plus CRISPR-Cas9 kinase-dead mutant with growth, invasion, and mouse virulence assays (T. gondii RH)","pmids":["39475314"],"confidence":"High","gaps":["No physiological substrate of the kinase identified","Nuclear signaling cascade downstream of catalysis undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2024,"claim":"Linking kinase function to TgSUB1 expression and micronemal protein processing supplied a mechanistic route from a nuclear kinase to the secretory-invasion defect.","evidence":"Transcriptomics on the kinase mutant plus micronemal protein processing assay (T. gondii RH)","pmids":["39475314"],"confidence":"High","gaps":["How TgTKL1 controls TgSUB1 transcription is unknown","TgSUB1 may be one of several relevant effectors among the >200 deregulated genes"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":null,"claim":"The direct substrates of TgTKL1 and the molecular pathway connecting its nuclear kinase activity to invasion-gene transcription remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No phosphorylation substrate identified","No structural model or role established for the plant-like EDR1 domain","Findings restricted to the RH strain"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Contains a plant-like Enhanced Disease Resistance 1 (EDR1) domain, a domain architecture found only in plants and protozoa [#1].","Kinase activity maintains expression of the subtilisin protease TgSUB1, required for post-exocytosis processing of micronemal proteins [#7].","Loss of TgTKL1 or its kinase activity impairs host cell attachment and microneme secretion/processing and abolishes progression through the lytic cycle [#2, #6].","Knockout and kinase-dead parasites are completely avirulent in the mouse model of acute toxoplasmosis [#4, #8]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"33581139","id":"PMC_33581139","title":"Protein kinases in Toxoplasma gondii.","date":"2021","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/33581139","citation_count":35,"is_preprint":false},{"pmid":"31996457","id":"PMC_31996457","title":"Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice.","date":"2020","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/31996457","citation_count":24,"is_preprint":false},{"pmid":"29559568","id":"PMC_29559568","title":"TgTKL1 Is a Unique Plant-Like Nuclear Kinase That Plays an Essential Role in Acute Toxoplasmosis.","date":"2018","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/29559568","citation_count":17,"is_preprint":false},{"pmid":"39475314","id":"PMC_39475314","title":"Kinase function of TgTKL1 is essential for its role in Toxoplasma propagation and pathogenesis.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/39475314","citation_count":2,"is_preprint":false},{"pmid":"38719028","id":"PMC_38719028","title":"TKL family kinases in human apicomplexan pathogens.","date":"2024","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/38719028","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6090,"output_tokens":1961,"usd":0.023842,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7252,"output_tokens":2553,"usd":0.050042,"stage2_stop_reason":"end_turn"},"total_usd":0.073884,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"TgTKL1 localizes to the nucleus in Toxoplasma gondii, as determined by endogenous tagging.\",\n      \"method\": \"Endogenous tagging / fluorescence localization\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by endogenous tagging, single lab, supported by functional studies in same paper\",\n      \"pmids\": [\"29559568\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TgTKL1 contains a plant-like Enhanced Disease Resistance 1 (EDR1) domain, a domain architecture unique to plants and protozoa.\",\n      \"method\": \"Bioinformatic domain analysis / sequence annotation\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — computational domain prediction, no functional mutagenesis of the domain reported in abstract\",\n      \"pmids\": [\"29559568\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockout of TgTKL1 causes specific impairment of host cell attachment, defects in microneme secretion and processing, and failure to progress through the lytic cycle.\",\n      \"method\": \"Genetic knockout / lytic cycle assay / attachment assay / microneme secretion assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with specific phenotypic readouts (attachment, microneme secretion/processing) and in vivo virulence, multiple orthogonal methods in one study\",\n      \"pmids\": [\"29559568\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TgTKL1 knockout parasites show differential expression of over 200 genes, including significant downregulation of multiple genes implicated in host cell attachment and invasion.\",\n      \"method\": \"Transcriptomics (RNA-seq) on TgTKL1 knockout parasites\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transcriptomics on clean KO, single lab, functional consequence (attachment/invasion) linked\",\n      \"pmids\": [\"29559568\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TgTKL1 knockout parasites are completely avirulent in mice infected intraperitoneally, establishing TgTKL1 as essential for acute toxoplasmosis.\",\n      \"method\": \"Mouse acute infection model with TgTKL1 knockout parasites\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO, in vivo virulence model, all mice survived; consistent with in vitro mechanistic findings\",\n      \"pmids\": [\"29559568\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TgTKL1 is a bona fide kinase, confirmed by in vitro kinase activity assay using purified recombinant TgTKL1 protein.\",\n      \"method\": \"In vitro kinase assay with purified recombinant protein\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro biochemical demonstration of kinase activity with recombinant protein, single lab\",\n      \"pmids\": [\"39475314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A TgTKL1 kinase-dead mutant (generated by CRISPR-Cas9 active-site mutagenesis) displays defects in parasite growth and host cell invasion identical to TgTKL1 knockout, establishing that catalytic kinase activity is required for TgTKL1 function.\",\n      \"method\": \"CRISPR-Cas9 active-site mutagenesis / kinase mutant strain / growth and invasion assays\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — active-site mutagenesis with in vitro phenotypic validation (growth, invasion) and in vivo virulence, multiple orthogonal readouts\",\n      \"pmids\": [\"39475314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Loss of TgTKL1 kinase function leads to downregulation of TgSUB1 (subtilisin 1) expression, resulting in defects in post-exocytosis processing of micronemal proteins, an event critical for host cell invasion.\",\n      \"method\": \"Transcriptomics on kinase mutant + micronemal protein processing assay\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mechanistic link from kinase function to transcriptional target (TgSUB1) to micronemal processing defect established by two orthogonal methods in one study\",\n      \"pmids\": [\"39475314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TgTKL1 kinase mutant parasites are completely avirulent in the mouse model of acute toxoplasmosis, confirming that kinase activity underlies the virulence function of TgTKL1.\",\n      \"method\": \"Mouse acute infection model with TgTKL1 kinase mutant parasites\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean kinase-dead mutant, in vivo virulence model, consistent with knockout data from prior study\",\n      \"pmids\": [\"39475314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    }\n  ],\n  \"current_model\": \"TgTKL1 is a nuclear, plant-like tyrosine kinase-like (TKL) family kinase in Toxoplasma gondii whose catalytic kinase activity is essential for parasite propagation: it maintains expression of invasion-related genes (including TgSUB1) through a nuclear signaling pathway, thereby enabling proper microneme secretion and post-exocytosis processing of micronemal proteins, host cell attachment, and invasion, and loss of TgTKL1 or its kinase activity renders parasites completely avirulent in mice.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgTKL1 is a nuclear tyrosine kinase-like family kinase in Toxoplasma gondii whose catalytic activity is essential for the lytic cycle and parasite virulence [#2, #5, #6]. Localizing to the parasite nucleus [#0], TgTKL1 acts as a signaling kinase whose activity sustains a transcriptional program required for host cell attachment and invasion: its loss deregulates over 200 genes, including downregulation of multiple invasion- and attachment-related genes [#3]. Mechanistically, kinase function maintains expression of the subtilisin protease TgSUB1, and its loss impairs post-exocytosis processing of micronemal proteins, a step critical for invasion [#7]. Consequently, TgTKL1 knockout or active-site kinase-dead parasites fail host cell attachment, show defective microneme secretion and processing, cannot progress through the lytic cycle, and are completely avirulent in mice [#2, #4, #6, #8]. How TgTKL1 nuclear signaling connects to its downstream transcriptional targets, and the identity of its direct phosphorylation substrates, have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where TgTKL1 acts and whether it is dispensable answered whether this kinase functions in nuclear signaling and is required for the parasite lytic cycle.\",\n      \"evidence\": \"Endogenous tagging/fluorescence localization plus genetic knockout with attachment, microneme secretion, and lytic cycle assays in T. gondii RH\",\n      \"pmids\": [\"29559568\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct kinase activity not yet demonstrated at this stage\", \"Mechanism linking nuclear localization to invasion defect unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Transcriptomics of the knockout linked TgTKL1 to a gene-expression program, framing it as a nuclear regulator of invasion-related genes rather than a purely structural or secretory factor.\",\n      \"evidence\": \"RNA-seq on TgTKL1 knockout parasites (T. gondii RH)\",\n      \"pmids\": [\"29559568\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect transcriptional targets not distinguished\", \"No DNA-binding or transcription-factor partner identified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Complete loss of virulence in mice established TgTKL1 as essential for acute toxoplasmosis in vivo, not merely for in vitro growth.\",\n      \"evidence\": \"Mouse intraperitoneal acute infection model with knockout parasites (T. gondii RH)\",\n      \"pmids\": [\"29559568\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether virulence loss stems from kinase activity was not tested at this stage\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"In vitro activity and active-site mutagenesis proved that the catalytic kinase function itself, not merely the protein's presence, drives growth, invasion, and virulence.\",\n      \"evidence\": \"In vitro kinase assay with purified recombinant protein plus CRISPR-Cas9 kinase-dead mutant with growth, invasion, and mouse virulence assays (T. gondii RH)\",\n      \"pmids\": [\"39475314\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No physiological substrate of the kinase identified\", \"Nuclear signaling cascade downstream of catalysis undefined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linking kinase function to TgSUB1 expression and micronemal protein processing supplied a mechanistic route from a nuclear kinase to the secretory-invasion defect.\",\n      \"evidence\": \"Transcriptomics on the kinase mutant plus micronemal protein processing assay (T. gondii RH)\",\n      \"pmids\": [\"39475314\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TgTKL1 controls TgSUB1 transcription is unknown\", \"TgSUB1 may be one of several relevant effectors among the >200 deregulated genes\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct substrates of TgTKL1 and the molecular pathway connecting its nuclear kinase activity to invasion-gene transcription remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No phosphorylation substrate identified\", \"No structural model or role established for the plant-like EDR1 domain\", \"Findings restricted to the RH strain\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004672\", \"supporting_discovery_ids\": [5, 6], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]},\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [5], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [3, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]},\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [2, 4, 8], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]},\n      {\"term_id\": \"GO:0007155\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Contains a plant-like Enhanced Disease Resistance 1 (EDR1) domain, a domain architecture found only in plants and protozoa [#1].\",\n      \"Kinase activity maintains expression of the subtilisin protease TgSUB1, required for post-exocytosis processing of micronemal proteins [#7].\",\n      \"Loss of TgTKL1 or its kinase activity impairs host cell attachment and microneme secretion/processing and abolishes progression through the lytic cycle [#2, #6].\",\n      \"Knockout and kinase-dead parasites are completely avirulent in the mouse model of acute toxoplasmosis [#4, #8].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_301270","name":"TKL1","product":"tyrosine kinase-like protein TKL1","uniprot_acc":"A0A125YK18","chromosome":"TGME49_chrIV","start_pos":2354847},{"strain":"GT1","gene_id":"TGGT1_301270","name":null,"product":"Tyrosine kinase-like (TKL) protein","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":2241797},{"strain":"RH88","gene_id":"TGRH88_009730","name":null,"product":"Tyrosine kinase-like (TKL) protein","uniprot_acc":null,"chromosome":"CM023085","start_pos":2540705},{"strain":"VEG","gene_id":"TGVEG_301270","name":null,"product":"Tyrosine kinase-like (TKL) protein","uniprot_acc":"V5AXL6","chromosome":"TGVEG_chrIV","start_pos":2389530}]}