PF3D7_1143500

PF3D7_1143500 (PfRCC-PIP) is an RCC1 motif-containing scaffold protein of Plasmodium falciparum that acts as a regulatory anchoring partner for the parasite Protein Phosphatase type-1 (PfPP1). It directly binds PfPP1 in vitro and forms a complex with PfPP1 in the parasite, ranking as a major PfPP1 interactor (PMID:30429842), and in a heterologous Xenopus oocyte system it engages endogenous PP1 and synergizes with suboptimal progesterone to promote oocyte maturation, indicating a positive regulatory effect on PP1 activity (PMID:30429842). Its RCC1 motif-containing region also binds the parasite kinase CDPK7, consistent with a role as a dual kinase- and phosphatase-anchoring scaffold (PMID:30429842), and attempted knock-out yielded no viable parasites, indicating the protein is required for blood-stage viability (PMID:30429842). Beyond these interaction and essentiality observations, no further mechanistic detail — substrate specificity, structural basis of binding, or in-parasite phosphoregulatory targets — has been characterized in the available corpus.

1. 2018 Medium

   Establishing whether PF3D7_1143500 physically partners a signaling enzyme addressed whether this RCC1-motif protein functions in phosphoregulation; it was shown to be a major direct binding partner of PfPP1 both in vitro and in the parasite.

   Evidence In vitro binding assay and co-immunoprecipitation from P. falciparum lysate

   PMID:30429842

   Open questions at the time

   • The structural basis and interaction interface with PfPP1 are not defined
   • Whether the interaction is constitutive or cell-cycle/stage-regulated is unknown
2. 2018 Medium

   To determine whether the PfPP1 interaction is functional rather than merely physical, the protein was tested in a heterologous system, showing it activates PP1-dependent oocyte maturation and thereby acts as a positive regulator of PP1 activity.

   Evidence Xenopus oocyte functional maturation assay with suboptimal progesterone

   PMID:30429842

   Open questions at the time

   • Regulatory effect on PfPP1 activity was inferred from a heterologous system, not measured on the parasite enzyme
   • The in-parasite substrates and dephosphorylation events controlled remain unidentified
3. 2018 Low

   Mapping partner binding to the RCC1 motif-containing region tested whether the scaffold engages more than one enzyme, revealing an interaction with the kinase CDPK7 and suggesting a dual kinase/phosphatase anchoring role.

   Evidence In vitro protein interaction assay with domain mapping

   PMID:30429842

   Open questions at the time

   • Single pulldown/binding assay without reciprocal or in-parasite validation
   • Functional consequence of CDPK7 anchoring is untested
   • Whether PfPP1 and CDPK7 binding are simultaneous or mutually exclusive is unknown
4. 2018 Low

   Attempted gene disruption addressed whether the protein is required for parasite survival, with failure to recover knock-outs indicating essentiality for blood-stage viability.

   Evidence Reverse genetics / attempted gene knock-out in P. falciparum

   PMID:30429842

   Open questions at the time

   • Essentiality inferred from a single failed KO attempt without conditional or complementation confirmation
   • The essential molecular function driving viability is not defined

• The in-parasite phosphoregulatory function of PF3D7_1143500 — its physiological PfPP1 substrates, the structural basis of PP1/CDPK7 binding, and its role across the parasite life cycle — remains unresolved.
• No substrate of the PfRCC-PIP/PfPP1 complex identified
• No structural model of the interactions
• Essentiality not confirmed by conditional depletion