VPS51

PF3D7_0103100 (VPS51) is a Plasmodium falciparum protein of largely uncharacterized function that, based on endogenous tagging, localizes to discrete foci in the parasite cytosol during asexual blood-stage development without consistent overlap with the K13 compartment (PMID:38039338). It is dispensable for in vitro asexual proliferation, as targeted gene disruption yielded viable parasites (PMID:38039338). VPS51 was recovered as a proximity-biotinylation hit using K13 and Eps15 as baits, placing it near, but not within, the K13 compartment protein network (PMID:38039338). Beyond this cytosolic focal localization and its dispensability for asexual growth, no direct enzymatic activity, binding partner, or defined trafficking role has been experimentally established for PF3D7_0103100 in the available corpus; its proposed membership in a GARP/VFT-type multi-subunit tethering complex rests on bioinformatic inference rather than functional data (PMID:24086721), and its transcript upregulation during zygote-to-ookinete development is transcriptomic only (PMID:36847501).

1. 2013 Low

   The first question was whether P. falciparum even encodes a VPS51-like tethering subunit, establishing candidate membership in a multi-subunit tethering complex.

   Evidence Comparative genomic analysis across 12 apicomplexan genomes

   PMID:24086721

   Open questions at the time

   • Computational inference only; no protein-level or functional validation of PF3D7_0103100
   • Reported sparse conservation of complex subunits across apicomplexa leaves complex assembly unconfirmed
   • No demonstrated binding partners for the predicted complex
2. 2023 Low

   Single-cell transcriptomics addressed when VPS51 is expressed, revealing stage-specific upregulation during early mosquito-stage development.

   Evidence Single-cell transcriptomics across zygote-to-ookinete pseudotime

   PMID:36847501

   Open questions at the time

   • Transcript-level data only, no protein or functional validation
   • Does not establish any trafficking role during the stage transition
   • No causal link between VPS51 expression and ookinete development
3. 2023 Medium

   Endogenous tagging and knockout tested where VPS51 acts and whether it is required, showing cytosolic foci distinct from the K13 compartment and dispensability for asexual growth.

   Evidence Endogenous 2xFKBP-GFP-2xFKBP tagging with fluorescence microscopy plus targeted gene disruption and in vitro growth assay

   PMID:38039338

   Open questions at the time

   • The identity and function of the cytosolic foci are undefined
   • No binding partner or cargo established for VPS51
   • Dispensability tested only for in vitro asexual stages; sexual/mosquito-stage roles untested
4. 2023 Low

   Proximity biotinylation asked whether VPS51 belongs to the K13 compartment network, placing it near K13/Eps15 but not confirming it as a bona fide K13 compartment protein.

   Evidence Proximity-dependent biotinylation (BioID) with K13 and Eps15 as baits

   PMID:38039338

   Open questions at the time

   • Single proximity-labeling experiment not corroborated by localization
   • Proximity does not establish direct interaction with K13 or Eps15
   • Functional relevance of the association is unknown

• The core molecular function of VPS51 remains open: no direct binding partner, tethering-complex assembly, cargo, or trafficking role has been experimentally demonstrated for PF3D7_0103100.
• No biochemical confirmation of GARP/VFT or other tethering-complex membership
• Nature and cargo of the cytosolic foci undefined
• No functional test in sexual or mosquito stages despite stage-specific transcript upregulation