PBANKA_0406600

PIC4 (PBANKA_0406600) is a candidate component of the PhIL1-associated inner membrane complex (IMC) in Plasmodium falciparum, identified solely through interaction proteomics: it was recovered as a candidate PhIL1 partner by immunoprecipitation/mass spectrometry of the gametocyte IMC (PMID:28985225) and again as a PhIL1-proximal protein in a BioID proximity-labelling screen in asexual blood-stage parasites (PMID:33830607). Both lines of evidence position PIC4 within the PhIL1 interaction neighborhood rather than assigning it an independent activity. Beyond its candidate membership in the PhIL1-associated IMC complex (PMID:28985225, PMID:33830607), no direct functional, structural, or localization data for PIC4 itself have been characterized in the available corpus.

1. 2017 Low

   To define the composition of the PhIL1-associated inner membrane complex, PIC4 was first placed in that complex as a candidate PhIL1 interactor, establishing its earliest association with the IMC.

   Evidence Immunoprecipitation followed by mass spectrometry of the gametocyte IMC in P. falciparum

   PMID:28985225

   Open questions at the time

   • Single Co-IP/MS experiment identifying PIC4 as a candidate; no reciprocal pulldown from PIC4 as bait
   • No direct localization of PIC4 to the IMC demonstrated
   • No functional role for PIC4 established
2. 2021 Low

   To test whether the PhIL1 association held in a different developmental stage and by an orthogonal method, PIC4 was recovered near PhIL1 in asexual blood-stage parasites, corroborating its candidate IMC-complex membership.

   Evidence BioID proximity-dependent biotin labelling with PhIL1 as bait, followed by mass spectrometry, in P. falciparum asexual blood stages

   PMID:33830607

   Open questions at the time

   • Proximity labelling identifies PIC4 as a candidate but does not confirm a direct interaction or IMC localization of PIC4
   • No functional validation (knockout, knockdown, tagging) of PIC4 itself
   • No structural or biochemical characterization of PIC4

• It remains unknown what PIC4 does at the molecular level, where it localizes, and whether it is functionally required, since all evidence to date is candidate-level interaction proteomics without direct characterization of PIC4 itself.
• No confirmed subcellular localization of PIC4
• No molecular activity or substrate identified for PIC4
• No genetic or phenotypic data (essentiality, stage-specific role) for PIC4