GET4

PF3D7_1438600 (GET4) is the P. falciparum homolog of Get4 and a component of the conserved Guided Entry of Tail-Anchored (GET) protein trafficking pathway, implicated in the post-translational membrane insertion of tail-anchored proteins in this parasite (PMID:34780541). Its assignment to this pathway rests on in vitro association studies showing that GET4 physically interacts with PfGet3, the parasite homolog of the GET pathway ATPase (PMID:34780541). Beyond this demonstrated association with PfGet3, no further mechanistic detail about GET4 itself—its structure, substrate range, or role in tail-anchored protein insertion—has been characterized in the available corpus.

1. 2021 Medium

   It was unknown whether P. falciparum encodes a functional GET pathway; identifying GET4 and its binding partner established that the parasite possesses a conserved tail-anchored protein insertion machinery.

   Evidence In vitro association/pull-down assay plus proximity labelling identifying GET pathway constituents in P. falciparum

   PMID:34780541

   Open questions at the time

   • Interaction shown by in vitro association without mutagenesis mapping the GET4–PfGet3 interface
   • No structural validation of GET4 or the GET4–PfGet3 complex
   • Functional role of GET4 in tail-anchored protein insertion not directly demonstrated in the parasite

• Whether GET4 is essential for tail-anchored protein targeting, which substrates it handles, and how it functions within the assembled GET complex in P. falciparum remain open.
• No loss-of-function or genetic essentiality data for GET4 in P. falciparum
• No identified tail-anchored substrates trafficked via GET4
• Stoichiometry and architecture of the parasite GET complex uncharacterized