{"gene":"PF3D7_1241200","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2022,"finding":"NUP269 (PF3D7_1241200) was identified as a component of the Plasmodium nuclear pore complex (NPC) by TurboID proximity labeling followed by affinity purification and mass spectrometry, using NUP313 as bait. GFP tagging confirmed its NPC localization. Gene deletion attempts indicated NUP269 is essential for parasite survival. NUP269 lacks primary sequence homology with proteins outside the Plasmodium genus, though it incorporates short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4.","method":"TurboID proximity labeling, affinity purification-mass spectrometry, GFP tagging (live imaging), gene deletion attempts","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labeling + MS + GFP localization + essentiality from deletion, single lab, multiple orthogonal methods","pmids":["36040030"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"NUP269 (PF3D7_1241200 / PBANKA_1454600) was identified as an interaction partner of PbNAB2 (a CCCH-type zinc finger protein) by immunoprecipitation-mass spectrometry, suggesting that NUP269 at the nuclear pore may participate in mRNA export in Plasmodium.","method":"Immunoprecipitation coupled to mass spectrometry (IP-MS) of PbNAB2::mCherry","journal":"Malaria journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS from a study focused on a different protein; NUP269 interaction is a secondary finding mentioned in the body text, not the main result","pmids":["38195464"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2025,"finding":"NUP269 (PF3D7_1241200) co-purified with the nuclear envelope protein SUN1 in Plasmodium berghei interactomics experiments, placing NUP269 in proximity to the SUN1-ALLAN complex at the nuclear envelope during male gametogenesis.","method":"Interactomics (co-purification/mass spectrometry) with SUN1 as bait","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — NUP269 co-purification is a secondary finding in a study focused on SUN1-ALLAN; single method, single lab","pmids":["40392232"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"NUP269 (PF3D7_1241200) is a Plasmodium-restricted nuclear pore complex component, confirmed by proximity labeling and GFP localization in P. berghei, essential for parasite survival, and identified as an interaction partner of the mRNA export factor PbNAB2 and the nuclear envelope protein SUN1, suggesting a role at the nuclear pore in nucleocytoplasmic transport."},"narrative":{"mechanistic_narrative":"NUP269 (PF3D7_1241200) is a Plasmodium-restricted component of the parasite nuclear pore complex, identified by TurboID proximity labeling with the nucleoporin NUP313 as bait, with GFP tagging confirming its localization at the nuclear pore and gene-deletion attempts indicating it is essential for parasite survival [PMID:36040030]. It lacks primary sequence homology to proteins outside the Plasmodium genus but contains short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4 [PMID:36040030]. Beyond its NPC membership, the direct molecular function of NUP269 itself has not been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Whether PF3D7_1241200 is a genuine nuclear pore component and whether it is required for parasite viability was unknown; proximity labeling, imaging, and deletion attempts established it as an essential Plasmodium-specific nucleoporin.","evidence":"TurboID proximity labeling with NUP313 bait, affinity purification-mass spectrometry, GFP live imaging, and gene deletion attempts","pmids":["36040030"],"confidence":"Medium","gaps":["No direct enzymatic or transport activity assigned to NUP269 itself","Structural homology to Nup155/Nup157/SMC4 is inferred from short domains, not experimentally resolved structure","Essentiality inferred from failed deletion, not conditional knockdown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"It was unknown whether NUP269 physically links to mRNA export machinery; a Co-IP placed it in proximity to the CCCH-type zinc finger protein PbNAB2, hinting at a role in nucleocytoplasmic mRNA transport.","evidence":"IP-MS of PbNAB2::mCherry","pmids":["38195464"],"confidence":"Low","gaps":["Single Co-IP from a study focused on PbNAB2; no reciprocal pulldown from NUP269","No functional demonstration that NUP269 participates in mRNA export","Direct versus indirect (whole-NPC) association not distinguished"],"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2025,"claim":"Whether NUP269 associates with nuclear envelope tethering machinery was untested; it co-purified with SUN1, placing it near the SUN1-ALLAN complex during male gametogenesis.","evidence":"Interactomics/co-purification mass spectrometry with SUN1 as bait","pmids":["40392232"],"confidence":"Low","gaps":["Secondary co-purification in a SUN1-focused study; not independently validated for NUP269","Functional role of NUP269 in gametogenesis not established","Proximity may reflect general NPC-nuclear envelope adjacency rather than specific interaction"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct molecular function of NUP269 within the nuclear pore — its structural role, transport substrates, and whether it actively mediates mRNA export or nuclear envelope tethering — remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimentally resolved structure or domain-function mapping","No demonstrated transport substrate or cargo","All partner associations are single-method co-purifications without functional follow-up"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Nuclear pore complex (NPC)"],"partners":["NUP313 (PROXIMITY LABELING BAIT)","PBNAB2 (CCCH-TYPE ZINC FINGER PROTEIN)","SUN1 (SUN1-ALLAN COMPLEX)"],"other_free_text":["Plasmodium-restricted; lacks primary sequence homology outside the genus but contains short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4 [#0]","Essential for parasite survival based on failed gene deletion [#0]","SUN1 co-purification observed during male gametogenesis [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36040030","id":"PMC_36040030","title":"TurboID Identification of Evolutionarily Divergent Components of the Nuclear Pore Complex in the Malaria Model Plasmodium berghei.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36040030","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38195464","id":"","title":"Characterization of a nuclear transport factor 2-like domain-containing protein in Plasmodium berghei.","date":"2024","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/38195464","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUP269"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40392232","id":"","title":"A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium berghei.","date":"2025","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/40392232","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUP269"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5273,"output_tokens":946,"usd":0.015005,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5652,"output_tokens":1819,"usd":0.036867,"stage2_stop_reason":"end_turn"},"total_usd":0.051872,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"NUP269 (PF3D7_1241200) was identified as a component of the Plasmodium nuclear pore complex (NPC) by TurboID proximity labeling followed by affinity purification and mass spectrometry, using NUP313 as bait. GFP tagging confirmed its NPC localization. Gene deletion attempts indicated NUP269 is essential for parasite survival. NUP269 lacks primary sequence homology with proteins outside the Plasmodium genus, though it incorporates short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4.\",\n      \"method\": \"TurboID proximity labeling, affinity purification-mass spectrometry, GFP tagging (live imaging), gene deletion attempts\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labeling + MS + GFP localization + essentiality from deletion, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"36040030\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NUP269 (PF3D7_1241200 / PBANKA_1454600) was identified as an interaction partner of PbNAB2 (a CCCH-type zinc finger protein) by immunoprecipitation-mass spectrometry, suggesting that NUP269 at the nuclear pore may participate in mRNA export in Plasmodium.\",\n      \"method\": \"Immunoprecipitation coupled to mass spectrometry (IP-MS) of PbNAB2::mCherry\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS from a study focused on a different protein; NUP269 interaction is a secondary finding mentioned in the body text, not the main result\",\n      \"pmids\": [\"38195464\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NUP269 (PF3D7_1241200) co-purified with the nuclear envelope protein SUN1 in Plasmodium berghei interactomics experiments, placing NUP269 in proximity to the SUN1-ALLAN complex at the nuclear envelope during male gametogenesis.\",\n      \"method\": \"Interactomics (co-purification/mass spectrometry) with SUN1 as bait\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — NUP269 co-purification is a secondary finding in a study focused on SUN1-ALLAN; single method, single lab\",\n      \"pmids\": [\"40392232\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"NUP269 (PF3D7_1241200) is a Plasmodium-restricted nuclear pore complex component, confirmed by proximity labeling and GFP localization in P. berghei, essential for parasite survival, and identified as an interaction partner of the mRNA export factor PbNAB2 and the nuclear envelope protein SUN1, suggesting a role at the nuclear pore in nucleocytoplasmic transport.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP269 (PF3D7_1241200) is a Plasmodium-restricted component of the parasite nuclear pore complex, identified by TurboID proximity labeling with the nucleoporin NUP313 as bait, with GFP tagging confirming its localization at the nuclear pore and gene-deletion attempts indicating it is essential for parasite survival [#0]. It lacks primary sequence homology to proteins outside the Plasmodium genus but contains short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4 [#0]. Beyond its NPC membership, the direct molecular function of NUP269 itself has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether PF3D7_1241200 is a genuine nuclear pore component and whether it is required for parasite viability was unknown; proximity labeling, imaging, and deletion attempts established it as an essential Plasmodium-specific nucleoporin.\",\n      \"evidence\": \"TurboID proximity labeling with NUP313 bait, affinity purification-mass spectrometry, GFP live imaging, and gene deletion attempts\",\n      \"pmids\": [\"36040030\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct enzymatic or transport activity assigned to NUP269 itself\",\n        \"Structural homology to Nup155/Nup157/SMC4 is inferred from short domains, not experimentally resolved structure\",\n        \"Essentiality inferred from failed deletion, not conditional knockdown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown whether NUP269 physically links to mRNA export machinery; a Co-IP placed it in proximity to the CCCH-type zinc finger protein PbNAB2, hinting at a role in nucleocytoplasmic mRNA transport.\",\n      \"evidence\": \"IP-MS of PbNAB2::mCherry\",\n      \"pmids\": [\"38195464\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP from a study focused on PbNAB2; no reciprocal pulldown from NUP269\",\n        \"No functional demonstration that NUP269 participates in mRNA export\",\n        \"Direct versus indirect (whole-NPC) association not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether NUP269 associates with nuclear envelope tethering machinery was untested; it co-purified with SUN1, placing it near the SUN1-ALLAN complex during male gametogenesis.\",\n      \"evidence\": \"Interactomics/co-purification mass spectrometry with SUN1 as bait\",\n      \"pmids\": [\"40392232\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Secondary co-purification in a SUN1-focused study; not independently validated for NUP269\",\n        \"Functional role of NUP269 in gametogenesis not established\",\n        \"Proximity may reflect general NPC-nuclear envelope adjacency rather than specific interaction\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of NUP269 within the nuclear pore — its structural role, transport substrates, and whether it actively mediates mRNA export or nuclear envelope tethering — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experimentally resolved structure or domain-function mapping\",\n        \"No demonstrated transport substrate or cargo\",\n        \"All partner associations are single-method co-purifications without functional follow-up\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017056\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006406\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Nuclear pore complex (NPC)\"\n    ],\n    \"partners\": [\n      \"NUP313 (proximity labeling bait)\",\n      \"PbNAB2 (CCCH-type zinc finger protein)\",\n      \"SUN1 (SUN1-ALLAN complex)\"\n    ],\n    \"other_free_text\": [\n      \"Plasmodium-restricted; lacks primary sequence homology outside the genus but contains short domains with structural homology to human Nup155/yeast Nup157 or condensin SMC4 [#0]\",\n      \"Essential for parasite survival based on failed gene deletion [#0]\",\n      \"SUN1 co-purification observed during male gametogenesis [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1241200","name":null,"product":"nucleoporin NUP269, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1454600","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1460300","name":null,"product":"nucleoporin NUP269, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NUP269","evaluation":null}