CACYBP

CACYBP (PF3D7_1238100) is a component of the Plasmodium falciparum SCF (PfSCF) ubiquitin E3 ligase complex, associating with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1, as established by immunoprecipitation and in vitro interaction assays coupled with a functional ubiquitination assay (PMID:38416790). In P. yoelii nigeriensis, the ortholog is a ~27 kDa protein expressed across all blood stages that adopts both monomer and dimer forms (PMID:36707015). Beyond its membership in the PfSCF complex (PMID:38416790) and these basic molecular properties of the P. yoelii nigeriensis ortholog (PMID:36707015), no substrate, catalytic contribution, or specific molecular function of CACYBP itself has been characterized in the available corpus.

1. 2023 Low

   To provide any biochemical footing for an uncharacterized parasite protein, the basic molecular properties of the CACYBP ortholog were defined, establishing its expression pattern and oligomeric behavior.

   Evidence Cloning, recombinant protein purification, and Western blot of parasite lysate in P. yoelii nigeriensis

   PMID:36707015

   Open questions at the time

   • Single lab establishing only size, oligomeric state, and stage expression; no functional mechanism established
   • No binding partners or complex context defined for the ortholog
   • Functional significance of monomer/dimer interconversion unknown
2. 2024 Medium

   To place CACYBP in a defined molecular pathway, it was tested for association with a candidate ubiquitin ligase, establishing it as a member of a functional SCF E3 ligase complex.

   Evidence Immunoprecipitation, in vitro protein-protein interaction assay, and ubiquitination assay in P. falciparum

   PMID:38416790

   Open questions at the time

   • The specific role of CACYBP within the PfSCF complex (e.g. substrate recognition, scaffolding, or regulation) is not defined
   • No CACYBP-dependent ubiquitination substrate identified
   • Single-lab characterization without reciprocal in vivo validation of CACYBP's requirement for complex activity

• What distinct molecular function CACYBP contributes to the PfSCF complex, and whether it targets specific substrates for ubiquitination, remains unestablished.
• No substrate or CACYBP-specific catalytic/adaptor role defined
• No structural model of CACYBP within the complex
• No genetic loss-of-function phenotype for CACYBP itself