Schematic of P. falciparum sumoylation pathway. P. falciparum orthologues for all members of the sumoylation pathway have been identified. The C-terminus of a mature SUMO (PF3D7_0505800) containing the glycine–glycine motif, is first activated by activating enzyme E1, a dimer of Uba 2 (PF3D7_1237000) and Aos1 (PF3D7_1144500), linking it by a thioester to a cysteine residue in Uba2. Activated SUMO is then transferred to a cysteine residue of E2, a SUMO-specific conjugating enzyme Ubc9 (PF3D7_0915100). In conjugation with SUMO ligases, Ubc9 conjugates SUMO to various substrate proteins. Target proteins contain SUMO motifs, whereby the SUMO binds to a specific lysine residue. Sumoylated substrates undergo de-conjugation via specific SUMO proteases, Ulp1(PFL1635w) and Ulp 2 (PFD 0970c Issar N, Roux E, Mattei D, Scherf A. Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments. Cell Microbiol. 2008 PMID: 18547337