{"gene":"TG_276990","gene_symbol":"MAPR","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2023,"finding":"TgMAPR is a hemoprotein containing a conserved heme-binding cytochrome b5 domain, identifying its biochemical nature as a cytochrome b5-type heme-binding protein.","method":"Sequence/domain analysis with experimental validation of hemoprotein identity","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical characterization of hemoprotein in a single study with domain-level validation","pmids":["37651449"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"TgMAPR localizes to the mitochondrion of Toxoplasma gondii, as determined by direct localization experiments.","method":"Subcellular localization (imaging/fractionation)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in a single lab, single paper","pmids":["37651449"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"TgMAPR physically interacts with the mitochondrial type I CYP450 enzyme TgCYP450mt, as demonstrated by in situ proximity ligation assays, establishing a binding partnership analogous to MAPR-CYP450 interactions in mammalian steroidogenesis.","method":"In situ proximity ligation assay","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity ligation assay in a single lab, single study","pmids":["37651449"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"Genetic ablation of TgMAPR (ΔTgMAPR) causes poor global fitness, loss of plasma membrane integrity, aberrant mitochondrial cristae, an abnormally long S-phase in the cell cycle, reduced steroid levels, and loss of virulence in mice, establishing TgMAPR as required for mitochondrial steroidogenesis and parasite fitness.","method":"Genetic knockout (ΔTgMAPR) with phenotypic readouts including growth assays, cell cycle analysis, metabolomics (steroid quantification), and mouse virulence assays","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean knockout with multiple orthogonal phenotypic and metabolomic readouts in a single rigorous study","pmids":["37651449"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"TgMAPR functions as part of a mitochondrial steroidogenic pathway in Toxoplasma gondii, supporting the production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone, as shown by reduced steroid levels in ΔTgMAPR parasites via metabolomics.","method":"LC-MS targeted lipidomics/metabolomics comparing ΔTgMAPR to wild-type parasites","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — metabolomics with genetic KO providing direct pathway placement, single lab with multiple orthogonal methods","pmids":["37651449"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMAPR is a mitochondrion-localized hemoprotein with a cytochrome b5 heme-binding domain that physically interacts with the mitochondrial CYP450 enzyme TgCYP450mt to support steroidogenesis in Toxoplasma gondii; loss of TgMAPR reduces parasite steroid levels and causes defects in membrane integrity, mitochondrial morphology, cell cycle progression, and virulence."},"narrative":{"mechanistic_narrative":"TgMAPR is a mitochondrion-localized cytochrome b5-type heme-binding protein that supports steroidogenesis in Toxoplasma gondii [PMID:37651449]. Through its conserved heme-binding cytochrome b5 domain it functions as a hemoprotein [PMID:37651449] and physically associates with the mitochondrial type I CYP450 enzyme TgCYP450mt, forming a redox partnership analogous to mammalian MAPR-CYP450 steroidogenic interactions [PMID:37651449]. This partnership sustains a mitochondrial steroidogenic pathway generating hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone [PMID:37651449]. Genetic ablation of TgMAPR reduces parasite steroid levels and produces pleiotropic defects—loss of plasma membrane integrity, aberrant mitochondrial cristae, an abnormally prolonged S-phase, poor fitness, and loss of virulence in mice—establishing the protein as required for parasite steroidogenesis and viability [PMID:37651449]. All available evidence derives from a single study; no additional mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing the biochemical identity of TgMAPR was needed to place it in a functional class; it was shown to be a cytochrome b5-type hemoprotein.","evidence":"Sequence/domain analysis with experimental validation of hemoprotein identity in Toxoplasma gondii","pmids":["37651449"],"confidence":"Medium","gaps":["Heme redox properties and electron-transfer chemistry not characterized","Domain-level validation only; no structural model"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Whether TgMAPR acts at a defined organelle was unknown; direct localization placed it at the mitochondrion, implicating it in mitochondrial biology.","evidence":"Subcellular localization by imaging/fractionation in Toxoplasma gondii","pmids":["37651449"],"confidence":"Medium","gaps":["Submitochondrial topology not resolved","Single-lab localization"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The molecular partner mediating TgMAPR's function was unknown; a physical interaction with the mitochondrial type I CYP450 enzyme TgCYP450mt identified its steroidogenic binding partner.","evidence":"In situ proximity ligation assay in Toxoplasma gondii","pmids":["37651449"],"confidence":"Medium","gaps":["Proximity assay without reciprocal biochemical validation","Direct electron/heme transfer to TgCYP450mt not demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The physiological requirement for TgMAPR was undefined; knockout linked its loss to a mitochondrial steroidogenic pathway and to pleiotropic fitness and virulence defects.","evidence":"Genetic knockout (ΔTgMAPR) with growth, cell-cycle, metabolomic steroid quantification, and mouse virulence assays in Toxoplasma gondii","pmids":["37651449"],"confidence":"High","gaps":["Causal chain from reduced steroids to membrane/mitochondrial/cell-cycle defects not dissected","Whether phenotypes are direct or downstream of steroid loss unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The specific metabolic output supported by TgMAPR was unknown; metabolomics placed it in production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone.","evidence":"LC-MS targeted metabolomics comparing ΔTgMAPR to wild-type parasites","pmids":["37651449"],"confidence":"High","gaps":["Enzymatic step catalyzed within the pathway not defined","Functional role of these steroids in the parasite unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgMAPR's heme chemistry mechanistically drives TgCYP450mt-dependent steroidogenesis, and how steroid loss produces the membrane, mitochondrial, and cell-cycle phenotypes, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstitution of the TgMAPR-TgCYP450mt catalytic cycle","Mechanistic link between steroids and downstream phenotypes untested","All findings from a single study"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGCYP450MT"],"other_free_text":["Cytochrome b5-type heme-binding domain protein (MAPR family) [#0]","Loss produces defects in plasma membrane integrity, mitochondrial cristae, S-phase progression, fitness, and mouse virulence [#3]","Supports production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone [#4]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37651449","id":"PMC_37651449","title":"Function and regulation of a steroidogenic CYP450 enzyme in the mitochondrion of Toxoplasma gondii.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37651449","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3125,"output_tokens":1193,"usd":0.013635,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6197,"output_tokens":2362,"usd":0.045018,"stage2_stop_reason":"end_turn"},"total_usd":0.058653,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"TgMAPR is a hemoprotein containing a conserved heme-binding cytochrome b5 domain, identifying its biochemical nature as a cytochrome b5-type heme-binding protein.\",\n      \"method\": \"Sequence/domain analysis with experimental validation of hemoprotein identity\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical characterization of hemoprotein in a single study with domain-level validation\",\n      \"pmids\": [\"37651449\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TgMAPR localizes to the mitochondrion of Toxoplasma gondii, as determined by direct localization experiments.\",\n      \"method\": \"Subcellular localization (imaging/fractionation)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in a single lab, single paper\",\n      \"pmids\": [\"37651449\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TgMAPR physically interacts with the mitochondrial type I CYP450 enzyme TgCYP450mt, as demonstrated by in situ proximity ligation assays, establishing a binding partnership analogous to MAPR-CYP450 interactions in mammalian steroidogenesis.\",\n      \"method\": \"In situ proximity ligation assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity ligation assay in a single lab, single study\",\n      \"pmids\": [\"37651449\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Genetic ablation of TgMAPR (ΔTgMAPR) causes poor global fitness, loss of plasma membrane integrity, aberrant mitochondrial cristae, an abnormally long S-phase in the cell cycle, reduced steroid levels, and loss of virulence in mice, establishing TgMAPR as required for mitochondrial steroidogenesis and parasite fitness.\",\n      \"method\": \"Genetic knockout (ΔTgMAPR) with phenotypic readouts including growth assays, cell cycle analysis, metabolomics (steroid quantification), and mouse virulence assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with multiple orthogonal phenotypic and metabolomic readouts in a single rigorous study\",\n      \"pmids\": [\"37651449\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TgMAPR functions as part of a mitochondrial steroidogenic pathway in Toxoplasma gondii, supporting the production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone, as shown by reduced steroid levels in ΔTgMAPR parasites via metabolomics.\",\n      \"method\": \"LC-MS targeted lipidomics/metabolomics comparing ΔTgMAPR to wild-type parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — metabolomics with genetic KO providing direct pathway placement, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"37651449\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgMAPR is a mitochondrion-localized hemoprotein with a cytochrome b5 heme-binding domain that physically interacts with the mitochondrial CYP450 enzyme TgCYP450mt to support steroidogenesis in Toxoplasma gondii; loss of TgMAPR reduces parasite steroid levels and causes defects in membrane integrity, mitochondrial morphology, cell cycle progression, and virulence.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgMAPR is a mitochondrion-localized cytochrome b5-type heme-binding protein that supports steroidogenesis in Toxoplasma gondii [#0, #1, #4]. Through its conserved heme-binding cytochrome b5 domain it functions as a hemoprotein [#0] and physically associates with the mitochondrial type I CYP450 enzyme TgCYP450mt, forming a redox partnership analogous to mammalian MAPR-CYP450 steroidogenic interactions [#2]. This partnership sustains a mitochondrial steroidogenic pathway generating hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone [#4]. Genetic ablation of TgMAPR reduces parasite steroid levels and produces pleiotropic defects—loss of plasma membrane integrity, aberrant mitochondrial cristae, an abnormally prolonged S-phase, poor fitness, and loss of virulence in mice—establishing the protein as required for parasite steroidogenesis and viability [#3]. All available evidence derives from a single study; no additional mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing the biochemical identity of TgMAPR was needed to place it in a functional class; it was shown to be a cytochrome b5-type hemoprotein.\",\n      \"evidence\": \"Sequence/domain analysis with experimental validation of hemoprotein identity in Toxoplasma gondii\",\n      \"pmids\": [\"37651449\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Heme redox properties and electron-transfer chemistry not characterized\", \"Domain-level validation only; no structural model\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether TgMAPR acts at a defined organelle was unknown; direct localization placed it at the mitochondrion, implicating it in mitochondrial biology.\",\n      \"evidence\": \"Subcellular localization by imaging/fractionation in Toxoplasma gondii\",\n      \"pmids\": [\"37651449\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Submitochondrial topology not resolved\", \"Single-lab localization\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The molecular partner mediating TgMAPR's function was unknown; a physical interaction with the mitochondrial type I CYP450 enzyme TgCYP450mt identified its steroidogenic binding partner.\",\n      \"evidence\": \"In situ proximity ligation assay in Toxoplasma gondii\",\n      \"pmids\": [\"37651449\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Proximity assay without reciprocal biochemical validation\", \"Direct electron/heme transfer to TgCYP450mt not demonstrated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The physiological requirement for TgMAPR was undefined; knockout linked its loss to a mitochondrial steroidogenic pathway and to pleiotropic fitness and virulence defects.\",\n      \"evidence\": \"Genetic knockout (\\u0394TgMAPR) with growth, cell-cycle, metabolomic steroid quantification, and mouse virulence assays in Toxoplasma gondii\",\n      \"pmids\": [\"37651449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Causal chain from reduced steroids to membrane/mitochondrial/cell-cycle defects not dissected\", \"Whether phenotypes are direct or downstream of steroid loss unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The specific metabolic output supported by TgMAPR was unknown; metabolomics placed it in production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone.\",\n      \"evidence\": \"LC-MS targeted metabolomics comparing \\u0394TgMAPR to wild-type parasites\",\n      \"pmids\": [\"37651449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Enzymatic step catalyzed within the pathway not defined\", \"Functional role of these steroids in the parasite unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgMAPR's heme chemistry mechanistically drives TgCYP450mt-dependent steroidogenesis, and how steroid loss produces the membrane, mitochondrial, and cell-cycle phenotypes, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstitution of the TgMAPR-TgCYP450mt catalytic cycle\", \"Mechanistic link between steroids and downstream phenotypes untested\", \"All findings from a single study\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0020037\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006694\", \"supporting_discovery_ids\": [3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006694\", \"supporting_discovery_ids\": [2, 3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgCYP450mt\"],\n    \"other_free_text\": [\n      \"Cytochrome b5-type heme-binding domain protein (MAPR family) [#0]\",\n      \"Loss produces defects in plasma membrane integrity, mitochondrial cristae, S-phase progression, fitness, and mouse virulence [#3]\",\n      \"Supports production of hydroxypregnenolone species, deoxycorticosterone, and dehydroepiandrosterone [#4]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_276990","name":"MAPR","product":"membrane-associated progesterone-binding protein homolog MAPR","uniprot_acc":"A0A125YP82","chromosome":"TGME49_chrXII","start_pos":6806157},{"strain":"GT1","gene_id":"TGGT1_276990","name":null,"product":"cytochrome b5 family heme/steroid binding domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":6715193},{"strain":"RH88","gene_id":"TGRH88_066330","name":null,"product":"cytochrome b5 family heme/steroid binding domain-containing protein","uniprot_acc":null,"chromosome":"CM023093","start_pos":6888222},{"strain":"VEG","gene_id":"TGVEG_276990","name":null,"product":"cytochrome b5 family heme/steroid binding domain-containing protein","uniprot_acc":"B6KRH3","chromosome":"TGVEG_chrXII","start_pos":6824740}]}