9.B.367.  The Plasmodium falciparum virulence factor trafficking system (PfVFTS) Family

After invading human red blood cells (RBCs), the malaria parasite Plasmodium falciparum remodels the host cell by trafficking proteins to the RBC compartment. The virulence protein, P. falciparum erythrocyte membrane protein 1 (PfEMP1; UniProt acc # K9KG67), is responsible for cytoadherence of infected cells to host endothelial receptors. This protein is exported across the parasite plasma membrane and parasitophorous vacuole membrane and inserted into the RBC membrane. PfEMP1 export through the infected RBC has been studied (Knuepfer et al. 2005), showing that a knob-associated histidine-rich protein (KAHRP) N-terminal protein export element appended to the PfEMP1 transmembrane and C-terminal domains is sufficient for efficient trafficking of protein domains to the outside of the P. falciparum-infected RBC. The physical state of the exported proteins suggested trafficking as a complex rather than in vesicles, and supports the hypothesis that endogenous PfEMP1 is trafficked in a similar manner. Also, the sequences required for expression of proteins to the outside of the P. falciparum-infected RBC membrane have been identified (Knuepfer et al. 2005).



Camus, D. and T.J. Hadley. (1985). A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science 230: 553-556.

Jaskiewicz, E., M. Jodłowska, R. Kaczmarek, and A. Zerka. (2019). Erythrocyte glycophorins as receptors for Plasmodium merozoites. Parasit Vectors 12: 317.

Knuepfer, E., M. Rug, N. Klonis, L. Tilley, and A.F. Cowman. (2005). Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes. Blood 105: 4078-4087.


TC#NameOrganismal TypeExample

Knob-associated histidine-rich protein, KAHRP, of 634 aas and 1 N-terminal TMS; plays a role in the transport of PfEMP1 from the P. falciparum cell to the RBC membrane (Knuepfer et al. 2005).

KAHRP of Plasmodium falciparum


Knob-associated His-rich protein of 659 aa

KAHP of Plasmodium vivax


Uncharacterized protein of 917 aas and 1 N-terminal TMS

UP of Plasmodium knowlesi


Erythrocyte-binding antigen 175, EBA-175, of 1435 aas and possibly two TMSs, N- and C-terminal. It may bind to human erythrocytes via glycophorin A (TC# 8.A.168.1.1) (Jaskiewicz et al. 2019). Binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans. EBA-175 may act as bridge between erythrocytes and merozoites (Camus and Hadley 1985).


EBA-175 of Plasmodium falciparum