{"gene":"TG_269290","gene_symbol":"NUP503","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2024,"finding":"TgNup503 (a nuclear pore component) physically interacts with TgTom40 (a mitochondrial protein translocon component), forming a molecular tether at a nuclear-mitochondrial membrane contact site in Toxoplasma gondii.","method":"Interaction/co-IP between nuclear pore and TOM translocon components, combined with genetic disruption (depletion) of TgNup503 and TgTom40 leading to contact site reduction","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction identified and supported by genetic disruption with defined morphological/functional readout, single lab, two orthogonal methods (interaction assay + genetic disruption)","pmids":["38456969"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"Genetic depletion of TgNup503 results in mitochondrial morphology defects and mitochondrial functional defects, demonstrating a role for TgNup503-mediated nuclear-mitochondrial contact sites in organelle communication.","method":"Conditional depletion/knockdown of TgNup503 with assessment of mitochondrial morphology and function as phenotypic readouts","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype (mitochondrial morphology and function), single lab, multiple readouts","pmids":["38456969"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgNup503 is a nuclear pore component in Toxoplasma gondii that interacts with the mitochondrial translocon protein TgTom40 to form a nuclear-mitochondrial membrane contact site, and its depletion reduces these contacts and causes mitochondrial morphology and functional defects, implicating it as a molecular tether mediating nuclear-mitochondrial communication."},"narrative":{"mechanistic_narrative":"TgNup503 is a nuclear pore component in Toxoplasma gondii that functions as a molecular tether establishing a nuclear-mitochondrial membrane contact site through physical interaction with the mitochondrial protein translocon component TgTom40 [PMID:38456969]. Genetic depletion of TgNup503 reduces these contact sites and produces mitochondrial morphology and functional defects, implicating TgNup503-mediated contacts in nuclear-mitochondrial organelle communication [PMID:38456969]. Beyond this tethering and organelle-communication role, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Whether a nuclear pore component physically bridges the nucleus and mitochondrion was unknown; identifying a reciprocal interaction between TgNup503 and the TOM translocon component TgTom40 established a defined molecular tether at a nuclear-mitochondrial membrane contact site.","evidence":"Co-IP/interaction assay between nuclear pore and TOM translocon components plus genetic disruption showing contact site reduction, in Toxoplasma gondii","pmids":["38456969"],"confidence":"Medium","gaps":["The interaction interface and whether binding is direct versus bridged by additional factors is not resolved","No structural model of the contact site is available","Stoichiometry and dynamics of the tether are uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Whether these contact sites are functionally important was unknown; conditional depletion of TgNup503 causing mitochondrial morphology and functional defects established that the tether mediates nuclear-mitochondrial organelle communication.","evidence":"Conditional depletion/knockdown of TgNup503 with mitochondrial morphology and function readouts in Toxoplasma gondii","pmids":["38456969"],"confidence":"Medium","gaps":["The molecular content exchanged across the contact site is not identified","Mechanism linking loss of contact to mitochondrial functional decline is unresolved","Whether the phenotype reflects loss of tethering versus a separate nuclear pore function is not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"What molecules or signals are transmitted across the TgNup503-TgTom40 contact site, and the structural basis of the tether, remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No cargo or signal transferred across the contact site identified","No structural characterization of the tether","Regulation of contact site formation is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGTOM40"],"other_free_text":["Functions as a molecular tether forming a nuclear-mitochondrial membrane contact site [#0]","Depletion reduces contact sites and impairs mitochondrial morphology and function [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"38456969","id":"PMC_38456969","title":"Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.","date":"2024","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38456969","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2825,"output_tokens":599,"usd":0.00873,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5306,"output_tokens":1539,"usd":0.032502,"stage2_stop_reason":"end_turn"},"total_usd":0.041232,"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\": 2024,\n      \"finding\": \"TgNup503 (a nuclear pore component) physically interacts with TgTom40 (a mitochondrial protein translocon component), forming a molecular tether at a nuclear-mitochondrial membrane contact site in Toxoplasma gondii.\",\n      \"method\": \"Interaction/co-IP between nuclear pore and TOM translocon components, combined with genetic disruption (depletion) of TgNup503 and TgTom40 leading to contact site reduction\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction identified and supported by genetic disruption with defined morphological/functional readout, single lab, two orthogonal methods (interaction assay + genetic disruption)\",\n      \"pmids\": [\"38456969\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Genetic depletion of TgNup503 results in mitochondrial morphology defects and mitochondrial functional defects, demonstrating a role for TgNup503-mediated nuclear-mitochondrial contact sites in organelle communication.\",\n      \"method\": \"Conditional depletion/knockdown of TgNup503 with assessment of mitochondrial morphology and function as phenotypic readouts\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype (mitochondrial morphology and function), single lab, multiple readouts\",\n      \"pmids\": [\"38456969\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgNup503 is a nuclear pore component in Toxoplasma gondii that interacts with the mitochondrial translocon protein TgTom40 to form a nuclear-mitochondrial membrane contact site, and its depletion reduces these contacts and causes mitochondrial morphology and functional defects, implicating it as a molecular tether mediating nuclear-mitochondrial communication.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgNup503 is a nuclear pore component in Toxoplasma gondii that functions as a molecular tether establishing a nuclear-mitochondrial membrane contact site through physical interaction with the mitochondrial protein translocon component TgTom40 [#0]. Genetic depletion of TgNup503 reduces these contact sites and produces mitochondrial morphology and functional defects, implicating TgNup503-mediated contacts in nuclear-mitochondrial organelle communication [#1]. Beyond this tethering and organelle-communication role, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether a nuclear pore component physically bridges the nucleus and mitochondrion was unknown; identifying a reciprocal interaction between TgNup503 and the TOM translocon component TgTom40 established a defined molecular tether at a nuclear-mitochondrial membrane contact site.\",\n      \"evidence\": \"Co-IP/interaction assay between nuclear pore and TOM translocon components plus genetic disruption showing contact site reduction, in Toxoplasma gondii\",\n      \"pmids\": [\"38456969\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"The interaction interface and whether binding is direct versus bridged by additional factors is not resolved\",\n        \"No structural model of the contact site is available\",\n        \"Stoichiometry and dynamics of the tether are uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether these contact sites are functionally important was unknown; conditional depletion of TgNup503 causing mitochondrial morphology and functional defects established that the tether mediates nuclear-mitochondrial organelle communication.\",\n      \"evidence\": \"Conditional depletion/knockdown of TgNup503 with mitochondrial morphology and function readouts in Toxoplasma gondii\",\n      \"pmids\": [\"38456969\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"The molecular content exchanged across the contact site is not identified\",\n        \"Mechanism linking loss of contact to mitochondrial functional decline is unresolved\",\n        \"Whether the phenotype reflects loss of tethering versus a separate nuclear pore function is not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"What molecules or signals are transmitted across the TgNup503-TgTom40 contact site, and the structural basis of the tether, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No cargo or signal transferred across the contact site identified\",\n        \"No structural characterization of the tether\",\n        \"Regulation of contact site formation is uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0044233\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007005\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgTom40\"],\n    \"other_free_text\": [\n      \"Functions as a molecular tether forming a nuclear-mitochondrial membrane contact site [#0]\",\n      \"Depletion reduces contact sites and impairs mitochondrial morphology and function [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_269290","name":"NUP503","product":"nucleoporin NUP503","uniprot_acc":"S8GIN8","chromosome":"TGME49_chrVIII","start_pos":5928490},{"strain":"GT1","gene_id":"TGGT1_269290","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":5927256},{"strain":"RH88","gene_id":"TGRH88_081980","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":11047287},{"strain":"VEG","gene_id":"TGVEG_269290","name":null,"product":"hypothetical protein","uniprot_acc":"V4Z880","chromosome":"TGVEG_chrVIII","start_pos":5944135}]}