PIC5

PIC5 (PF3D7_1310700) is an inner membrane complex (IMC) protein of Plasmodium falciparum identified as a PhIL1-interacting candidate across asexual blood-stage and sexual (gametocyte) parasites (PMID:33830607, PMID:28985225). It was first recovered as an uncharacterized protein enriched by BioID proximity labeling using PhIL1 as bait in asexual blood stages, and endogenous GFP-tagging confirmed its localization to the IMC (PMID:33830607). Immunoprecipitation of the PhIL1 complex placed PIC5 within the PhIL1-associated protein complex that co-exists with the glideosome motor complex in merozoites (PMID:34324609) and within the gametocyte IMC (PMID:28985225). Beyond its membership in the PhIL1-associated IMC complex and its IMC localization, no independent molecular function, substrate, or phenotype has been characterized for PIC5 itself in the available corpus.

1. 2017 Low

   The first question was whether PF3D7_1310700 associates with the IMC machinery in a specific developmental stage; identifying it in the gametocyte PhIL1 complex established it as a candidate component of the sexual-stage IMC.

   Evidence Immunoprecipitation and mass spectrometry of the PhIL1 complex in P. falciparum gametocytes

   PMID:28985225

   Open questions at the time

   • Single Co-IP/MS identifying PIC5 as a candidate; no reciprocal pulldown or direct-interaction validation
   • No functional characterization of PIC5 itself in gametocytes
   • Localization not independently confirmed by tagging in this study
2. 2021 Medium

   Whether PF3D7_1310700 is a genuine IMC protein in asexual blood stages was unresolved; proximity labeling with PhIL1 plus endogenous tagging established both its physical proximity to PhIL1 and its IMC localization.

   Evidence BioID proximity-dependent biotinylation with PhIL1 as bait plus endogenous GFP-tagging and fluorescence microscopy in asexual blood-stage P. falciparum

   PMID:33830607

   Open questions at the time

   • Proximity labeling does not demonstrate a direct binary interaction with PhIL1
   • No genetic knockdown/knockout to define a functional role
   • Molecular activity of PIC5 remains undefined
3. 2021 Low

   Whether PF3D7_1310700 belongs to the motility-associated IMC machinery of invasive stages was addressed by placing it in the PhIL1-associated complex that co-exists with the glideosome motor in merozoites.

   Evidence Co-immunoprecipitation and mass spectrometry using PhIL1 as bait in P. falciparum merozoites

   PMID:34324609

   Open questions at the time

   • Single Co-IP without PIC5-specific functional follow-up
   • Relationship of PIC5 to glideosome function not tested
   • Does not establish whether PIC5 is required for complex assembly or motility

• The intrinsic molecular function of PIC5, and whether it is required for IMC integrity, gliding motility, invasion, or gametocyte development, remains unknown.
• No loss-of-function phenotype for PIC5
• No defined molecular activity or direct binding partner
• No structural or domain-level characterization