PF3D7_0711500

PF3D7_0711500 is a nuclear protein of Plasmodium falciparum, identified by nuclear-fraction proteomics and confirmed with tagged transgenic lines (PMID:23181666). Named PfRCC-PIP, it functions as a dual anchoring scaffold: it directly binds the parasite Protein Phosphatase type-1 (PfPP1) both in vitro and in the parasite, and the region containing its RCC1 motifs also engages the parasite kinase CDPK7, positioning it to bridge a phosphatase and a kinase (PMID:30429842). Attempted knockout yielded no viable parasites, consistent with a role essential for asexual survival (PMID:30429842). Beyond these interaction and localization findings, the downstream substrates and the biological consequence of the PfPP1/CDPK7 anchoring have not been characterized in the available corpus.

1. 2012 Medium

   Whether PF3D7_0711500 resides in a specific subcellular compartment was unknown; establishing nuclear localization provided the first functional context for this putative RCC1-motif protein.

   Evidence High-accuracy mass spectrometry of P. falciparum nuclear fractions with transgenic tagged-line validation

   PMID:23181666

   Open questions at the time

   • Functional consequence of nuclear localization not tested for this protein
   • No cell-cycle or chromatin association demonstrated
   • Interaction partners unidentified at this stage
2. 2018 Medium

   It was unknown what molecular partners PF3D7_0711500 engaged; direct binding to PfPP1 and to CDPK7 via its RCC1-motif region established it as a dual kinase/phosphatase anchoring scaffold (PfRCC-PIP).

   Evidence In vitro binding assay, co-immunoprecipitation from parasite lysate, and Xenopus oocyte PP1 regulatory assay

   PMID:30429842

   Open questions at the time

   • Substrates dephosphorylated/phosphorylated within the complex not identified
   • Biological process coordinated by the anchoring not defined
   • Structural basis of RCC1-motif binding to CDPK7 not resolved
3. 2018 Low

   Whether the gene is required for parasite growth was untested; failure to recover knockout parasites indicated it is likely essential for survival.

   Evidence Reverse genetics / attempted gene knockout in P. falciparum

   PMID:30429842

   Open questions at the time

   • Single failed-KO approach without a conditional system to rigorously confirm essentiality
   • Stage-specific requirement not defined
   • No phenotype from controlled depletion

• The downstream substrates and the cellular process coordinated by the PfPP1/CDPK7 anchoring function of PF3D7_0711500 remain unknown.
• No substrate of the anchored phosphatase/kinase identified
• No conditional-depletion phenotype linking the scaffold to a specific pathway
• No structural model of the complex