Affinage · Plasmodium

RCC-PIP

PF3D7_0919900 · regulator of chromosome condensation-PP1-interacting protein

Annotated
2026-09-08
20 papers in source corpus 1 papers cited in narrative 1 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RCC-PIP (PF3D7_0919900) is a dual-anchoring scaffold protein in Plasmodium falciparum that bridges a phosphatase and a kinase, and appears essential for blood-stage parasite survival (PMID:30429842). It directly interacts with the phosphatase PfPP1 in vitro and is present in complex with PfPP1 in parasite extracts; in a Xenopus oocyte system it binds endogenous PP1 and, in synergy with suboptimal progesterone, triggers oocyte maturation, indicating a regulatory, activating effect on PP1 (PMID:30429842). Its RCC1-motif-containing region additionally binds the calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein (PMID:30429842). Reverse genetic studies failed to yield viable knock-out parasites, consistent with an essential role in intraerythrocytic survival (PMID:30429842). Beyond (PMID:30429842), no further mechanistic detail — including structural basis of binding, mutagenesis of interaction motifs, or defined pathway position — has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2018 Medium

    Whether PF3D7_0919900 acts as a regulator of the parasite phosphatase PfPP1 was unknown; this work established it as a direct PP1-interacting protein that modulates PP1 activity and simultaneously anchors the kinase CDPK7, defining it as a dual kinase/phosphatase scaffold essential for blood-stage growth.

    Evidence In vitro pull-down and reciprocal co-immunoprecipitation from parasite extracts, Xenopus oocyte functional maturation assay, direct binding of recombinant CDPK7, and failed knock-out by reverse genetics

    PMID:30429842

    Open questions at the time
    • No structural model or mutagenesis of the PP1- or CDPK7-binding motifs to define contact residues
    • The biochemical consequence of RCC-PIP anchoring on CDPK7 activity and on PP1 in the native parasite is undefined
    • The pathway context and substrates coordinated by this kinase-phosphatase scaffold remain unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RCC-PIP integrates PfPP1 and CDPK7 signaling to support intraerythrocytic survival, and which downstream substrates it regulates, remains unresolved.
  • No conditional knockdown to define the essential function underlying the failed knock-out
  • No identification of substrates or the cellular process controlled by the scaffold
  • No structural characterization of the RCC1-repeat interaction interfaces

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CDPK7 (CALCIUM-DEPENDENT PROTEIN KINASE 7)PFPP1 (PROTEIN PHOSPHATASE 1)
Complex memberships
RCC-PIP–PfPP1 complex (in parasite extracts and in vitro)

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 PF3D7_0919900 (RCC-PIP) directly interacts with PfPP1 in vitro and is present in complex with PfPP1 in P. falciparum parasite extracts. In a Xenopus oocyte model, RCC-PIP interacts with endogenous PP1 and acts in synergy with suboptimal doses of progesterone to trigger oocyte maturation, indicating a regulatory (activating/modulatory) effect on PP1. Reverse genetic studies failed to produce viable knock-out parasites, suggesting an essential role in blood-stage survival. Additionally, the RCC1-motif-containing region of RCC-PIP was shown to interact with the parasite calcium-dependent protein kinase CDPK7, establishing RCC-PIP as both a phosphatase- and kinase-anchoring protein. In vitro pull-down, co-immunoprecipitation from parasite extracts, Xenopus oocyte functional assay, reverse genetics (failed KO), direct binding assay with recombinant CDPK7 Frontiers in microbiology Medium 30429842

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference. Malaria journal 58 12057017
2020 Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes. Nature communications 40 32669539
2006 Protein phosphatase 1, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites. Cellular microbiology 40 16548885
2006 Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine-rich repeat protein of the human malaria parasite Plasmodium falciparum. Molecular microbiology 34 16629662
2002 Plasmodium falciparum protein phosphatase type 1 functionally complements a glc7 mutant in Saccharomyces cerevisiae. International journal for parasitology 30 12062492
2013 Plasmodium falciparum encodes a conserved active inhibitor-2 for Protein Phosphatase type 1: perspectives for novel anti-plasmodial therapy. BMC biology 27 23837822
2021 Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages. Communications biology 18 34145386
2011 Plasmodium falciparum inhibitor-3 homolog increases protein phosphatase type 1 activity and is essential for parasitic survival. The Journal of biological chemistry 18 22128182
2019 Essential role of GEXP15, a specific Protein Phosphatase type 1 partner, in Plasmodium berghei in asexual erythrocytic proliferation and transmission. PLoS pathogens 15 31348803
2014 Identification of a Plasmodium falciparum inhibitor-2 motif involved in the binding and regulation activity of protein phosphatase type 1. The FEBS journal 14 25132288
2016 Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1. Frontiers in microbiology 12 27303372
2020 The Multifaceted Role of Protein Phosphatase 1 in Plasmodium. Trends in parasitology 11 33036936
2018 Characterization of a Protein Phosphatase Type-1 and a Kinase Anchoring Protein in Plasmodium falciparum. Frontiers in microbiology 11 30429842
2019 Plasmodium pseudo-Tyrosine Kinase-like binds PP1 and SERA5 and is exported to host erythrocytes. Scientific reports 9 31148576
2025 The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole. PLoS pathogens 7 39808636
2022 Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development. Open biology 5 35920043
2016 Phosphatases are emerging as novel druggable targets in Plasmodium. Future microbiology 4 27159136
2022 Mapping PP1c and Its Inhibitor 2 Interactomes Reveals Conserved and Specific Networks in Asexual and Sexual Stages of Plasmodium. International journal of molecular sciences 3 35162991
2023 Characterization of GEXP15 as a Potential Regulator of Protein Phosphatase 1 in Plasmodium falciparum. International journal of molecular sciences 1 37628837
2025 Plasmodium falciparum PP1 phosphatase is a key regulator of malaria parasite transmission. mBio 0 40823845