NUP269

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.

1. 2022 Medium

   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

   PMID:36040030

   Open questions at the time

   • 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
2. 2024 Low

   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

   PMID:38195464

   Open questions at the time

   • 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
3. 2025 Low

   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

   PMID:40392232

   Open questions at the time

   • 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

• 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.
• 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