{"gene":"PF3D7_0317300","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2022,"finding":"NUP335 (PF3D7_0317300) 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 NPC localization. Gene deletion attempts indicate NUP335 is essential to parasite survival. NUP335 lacks primary sequence homology with proteins outside the Plasmodium genus.","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 with MS and GFP localization confirmation, single lab, two orthogonal methods (proteomics + imaging + genetic essentiality)","pmids":["36040030"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"NUP335 (PF3D7_0317300) co-purified with SUN1, a conserved nuclear envelope protein, placing NUP335 in proximity to the SUN1-ALLAN complex at the nuclear envelope during male gametogenesis in P. berghei. This co-purification was detected by interactomics and suggests NUP335-containing nuclear pores are associated with the SUN1 complex that coordinates MTOC dynamics at the nuclear envelope.","method":"Interactomics (co-purification/mass spectrometry), live-cell imaging, ultrastructural expansion microscopy","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-purification result mentioning NUP335 incidentally within a study focused on SUN1 and ALLAN; no direct functional experiment performed on NUP335 itself","pmids":["40392232"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"NUP335 (PF3D7_0317300) is an essential, Plasmodium-specific component of the nuclear pore complex in P. berghei, identified by TurboID proximity labeling and confirmed by GFP localization, with no primary sequence homology outside the Plasmodium genus; it also co-purifies with the nuclear envelope protein SUN1, suggesting its NPC is physically associated with the SUN1-containing LINC-like complex at the nuclear envelope."},"narrative":{"mechanistic_narrative":"NUP335 (PF3D7_0317300) is an essential, Plasmodium-specific component of the nuclear pore complex (NPC), identified in P. berghei by TurboID proximity labeling with the nucleoporin NUP313 as bait and confirmed to localize to the NPC by GFP tagging; gene deletion attempts indicate it is essential for parasite survival, and it lacks primary sequence homology to proteins outside the Plasmodium genus [PMID:36040030]. Beyond its membership in the NPC and a single co-purification with the nuclear envelope protein SUN1 during male gametogenesis in P. berghei [PMID:40392232], no direct molecular function, substrate, or mechanism has been characterized for NUP335 itself in the available corpus.","teleology":[{"year":2022,"claim":"Whether PF3D7_0317300 is part of the Plasmodium nuclear pore was unknown; proximity labeling from a known nucleoporin bait placed it within the NPC and established it as an essential, genus-restricted component.","evidence":"TurboID proximity labeling with NUP313 bait, affinity purification/mass spectrometry, GFP live imaging, and gene deletion attempts in P. berghei","pmids":["36040030"],"confidence":"Medium","gaps":["No direct biochemical activity or transport function assigned to NUP335 itself","Structural position within the NPC and direct binding partners not resolved","Essentiality inferred from failed deletion, not from conditional knockdown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Whether the NUP335-containing NPC physically associates with the nuclear envelope LINC-like machinery was untested; co-purification with SUN1 placed NUP335 in proximity to the SUN1 complex during male gametogenesis.","evidence":"Interactomics/co-purification with mass spectrometry, live-cell imaging, and ultrastructural expansion microscopy in P. berghei, in a study focused on SUN1 and ALLAN","pmids":["40392232"],"confidence":"Low","gaps":["Single incidental co-purification within a SUN1/ALLAN-focused study; no direct functional experiment on NUP335","No reciprocal pulldown or direct interaction validation for NUP335","Functional consequence of the NPC-SUN1 association for NUP335 not tested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct molecular function of NUP335, its structural role within the NPC, and its specific binding partners remain unresolved beyond membership in the pore complex.","evidence":"No further mechanistic evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No defined molecular activity for NUP335","No mapped direct protein-protein interfaces within the NPC","No conditional depletion to define its role in nucleocytoplasmic transport or nuclear organization"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Nuclear pore complex (NPC)"],"partners":["NUP313 (PROXIMITY-LABELING BAIT)","SUN1 (CO-PURIFICATION)"],"other_free_text":["Essential for parasite survival in P. berghei (gene deletion attempts failed) [#0]","Plasmodium-specific: no primary sequence homology outside the Plasmodium genus [#0]","Co-purifies with SUN1 during male gametogenesis, associating the NPC with the SUN1-ALLAN nuclear envelope complex [#1]"]}},"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":"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":["NUP335"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4636,"output_tokens":717,"usd":0.012332,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5355,"output_tokens":1500,"usd":0.032137,"stage2_stop_reason":"end_turn"},"total_usd":0.044469,"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\": \"NUP335 (PF3D7_0317300) 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 NPC localization. Gene deletion attempts indicate NUP335 is essential to parasite survival. NUP335 lacks primary sequence homology with proteins outside the Plasmodium genus.\",\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 with MS and GFP localization confirmation, single lab, two orthogonal methods (proteomics + imaging + genetic essentiality)\",\n      \"pmids\": [\"36040030\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NUP335 (PF3D7_0317300) co-purified with SUN1, a conserved nuclear envelope protein, placing NUP335 in proximity to the SUN1-ALLAN complex at the nuclear envelope during male gametogenesis in P. berghei. This co-purification was detected by interactomics and suggests NUP335-containing nuclear pores are associated with the SUN1 complex that coordinates MTOC dynamics at the nuclear envelope.\",\n      \"method\": \"Interactomics (co-purification/mass spectrometry), live-cell imaging, ultrastructural expansion microscopy\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-purification result mentioning NUP335 incidentally within a study focused on SUN1 and ALLAN; no direct functional experiment performed on NUP335 itself\",\n      \"pmids\": [\"40392232\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"NUP335 (PF3D7_0317300) is an essential, Plasmodium-specific component of the nuclear pore complex in P. berghei, identified by TurboID proximity labeling and confirmed by GFP localization, with no primary sequence homology outside the Plasmodium genus; it also co-purifies with the nuclear envelope protein SUN1, suggesting its NPC is physically associated with the SUN1-containing LINC-like complex at the nuclear envelope.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP335 (PF3D7_0317300) is an essential, Plasmodium-specific component of the nuclear pore complex (NPC), identified in P. berghei by TurboID proximity labeling with the nucleoporin NUP313 as bait and confirmed to localize to the NPC by GFP tagging; gene deletion attempts indicate it is essential for parasite survival, and it lacks primary sequence homology to proteins outside the Plasmodium genus [#0]. Beyond its membership in the NPC and a single co-purification with the nuclear envelope protein SUN1 during male gametogenesis in P. berghei [#1], no direct molecular function, substrate, or mechanism has been characterized for NUP335 itself in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether PF3D7_0317300 is part of the Plasmodium nuclear pore was unknown; proximity labeling from a known nucleoporin bait placed it within the NPC and established it as an essential, genus-restricted component.\",\n      \"evidence\": \"TurboID proximity labeling with NUP313 bait, affinity purification/mass spectrometry, GFP live imaging, and gene deletion attempts in P. berghei\",\n      \"pmids\": [\"36040030\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical activity or transport function assigned to NUP335 itself\",\n        \"Structural position within the NPC and direct binding partners not resolved\",\n        \"Essentiality inferred from failed deletion, not from conditional knockdown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the NUP335-containing NPC physically associates with the nuclear envelope LINC-like machinery was untested; co-purification with SUN1 placed NUP335 in proximity to the SUN1 complex during male gametogenesis.\",\n      \"evidence\": \"Interactomics/co-purification with mass spectrometry, live-cell imaging, and ultrastructural expansion microscopy in P. berghei, in a study focused on SUN1 and ALLAN\",\n      \"pmids\": [\"40392232\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single incidental co-purification within a SUN1/ALLAN-focused study; no direct functional experiment on NUP335\",\n        \"No reciprocal pulldown or direct interaction validation for NUP335\",\n        \"Functional consequence of the NPC-SUN1 association for NUP335 not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of NUP335, its structural role within the NPC, and its specific binding partners remain unresolved beyond membership in the pore complex.\",\n      \"evidence\": \"No further mechanistic evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No defined molecular activity for NUP335\",\n        \"No mapped direct protein-protein interfaces within the NPC\",\n        \"No conditional depletion to define its role in nucleocytoplasmic transport or nuclear organization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Nuclear pore complex (NPC)\"],\n    \"partners\": [\"NUP313 (proximity-labeling bait)\", \"SUN1 (co-purification)\"],\n    \"other_free_text\": [\n      \"Essential for parasite survival in P. berghei (gene deletion attempts failed) [#0]\",\n      \"Plasmodium-specific: no primary sequence homology outside the Plasmodium genus [#0]\",\n      \"Co-purifies with SUN1 during male gametogenesis, associating the NPC with the SUN1-ALLAN nuclear envelope complex [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0317300","name":null,"product":"nucleoporin NUP335, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0807900","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0824500","name":null,"product":"nucleoporin NUP335, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NUP335","evaluation":null}