PF3D7_1313300

PF3D7_1313300 is annotated as a member of the Plasmodium falciparum cyclophilin family, a group of putative peptidyl-prolyl cis-trans isomerases and/or molecular chaperones assessed collectively by recombinant biochemistry (PMID:22546550, PMID:21549842). In P. falciparum extracts, cyclophilin-attributable PPIase activity is inhibited by cyclosporin A but not FK506 or rapamycin, and the cyclosporin A-bound cyclophilin fraction inhibits calcineurin phosphatase activity in vitro; however, this activity derives from an unresolved cyclophilin mixture and is not specifically assigned to PF3D7_1313300 (PMID:7520696). Across the recombinantly expressed family, only two of eight members showed PPIase activity while all eight showed chaperone activity, but the abstracts do not resolve which activity profile belongs to PF3D7_1313300 individually (PMID:22546550, PMID:21549842). In P. berghei, the ortholog of PF3D7_1313300 was recovered as a candidate interactor of the PP1c/inhibitor-2 phosphatase regulatory complex in both asexual and sexual stages by affinity pulldown-mass spectrometry (PMID:35162991). Beyond family-level membership and this single co-purification, no experiment has directly characterized the enzymatic activity, binding partners, structure, or in-parasite function of PF3D7_1313300 itself in the available corpus.

1. 1994 Medium

   Establishing whether P. falciparum harbors cyclosporin A-sensitive PPIase activity distinguished cyclophilins from FKBPs as the drug-relevant isomerases and linked this activity to calcineurin regulation, but did not resolve which of many cyclophilins was responsible.

   Evidence In vitro PPIase assay with an inhibitor panel and a calcineurin phosphatase inhibition assay on P. falciparum cell-free extracts

   PMID:7520696

   Open questions at the time

   • Activity attributed to an unresolved cyclophilin mixture, not to PF3D7_1313300 specifically
   • No demonstration that PF3D7_1313300 contributes to the calcineurin-inhibitory activity
   • No in-parasite functional assignment
2. 2011 Low

   Recombinant production of all 11 P. falciparum cyclophilin/cyclophilin-like proteins, including PF3D7_1313300, under a uniform system enabled family-wide folding and cyclosporin A binding comparison, but did not report PF3D7_1313300-specific results.

   Evidence Recombinant expression and purification in E. coli with thermal melt assays for folding and cyclosporin A binding

   PMID:21549842

   Open questions at the time

   • Abstract does not report specific folding or cyclosporin A binding data for PF3D7_1313300
   • No enzymatic characterization
   • No structural model
3. 2012 Low

   Orthogonal PPIase and chaperone assays across eight recombinant family members showed the family is functionally split (isomerase-active minority, chaperone-active majority), but the specific activity of PF3D7_1313300 was not distinguished.

   Evidence In vitro PPIase activity assay and thermal aggregation prevention chaperone assay on recombinant proteins

   PMID:22546550

   Open questions at the time

   • Whether PF3D7_1313300 is one of the two PPIase-active members is unstated
   • No substrate identity
   • No in-parasite validation of chaperone or isomerase role
4. 2022 Low

   Interactome mapping of the PP1c/inhibitor-2 phosphatase complex provided the first candidate physiological context for the PF3D7_1313300 ortholog, placing it near a phosphatase regulatory hub across asexual and sexual stages.

   Evidence mCherry-tagged PP1c and I2 affinity pulldown from P. berghei transgenic parasites followed by mass spectrometry

   PMID:35162991

   Open questions at the time

   • Co-purification not validated as a direct physical interaction
   • Shown for the P. berghei ortholog, not P. falciparum PF3D7_1313300 directly
   • Functional consequence of the association is unknown

• The direct enzymatic activity, substrates, binding partners, structure, and in-parasite function of PF3D7_1313300 itself remain uncharacterized, as all current evidence is either family-level or from an ortholog co-purification.
• No member-specific PPIase or chaperone activity established for PF3D7_1313300
• No genetic knockout/knockdown phenotype in either species
• No validated direct binding partner for PF3D7_1313300