Table 3.

Comparative analyses of key features of protozoa metacaspases.

Features	Leishmania metacaspases	Trypanosoma metacaspases	Plasmodium metacaspases
Cys/His Catalytic dyad	All metacaspases contain His/Cys dyad.	TbMCA2, TbMCA3, TbMCA5, TcMCA5 and TcMCA3 possess His/Cys dyad (McLuskey et al., 2014)	MCA-1 and -2 of P. vivax, P. falciparum and P. berghi have His/Cys dyad. PvMCA-3 has Cys/His catalytic dyad, but it is absent in PfMCA-3 and PbMCA-3.
Localization/ Expression	LdMC1 and LdMC2 expressed in promastigote and axenic amastigote forms. LmjMCA located in the mitochondrion and associated with the mitotic spindle (Castanys-Muñoz et al., 2012).	TbMCA-2, TbMCA-3, and TbMCA-4 expressed in bloodstream stage only. TbMCA-5 expressed in both life cycle stages. TbMCA-2, TbMCA-3, and TbMCA-5 were located predominantly in endosomes associated with RAB11.	PfMCA-1 and PvMCA-1 gene expressed during asexual stages (Meslin et al., unpublished observations). PbMCA-1 expression was detected in female gametocytes, oocysts, and sporozoites. PfMCA-2 was localized in schizonts and gametocytes stages I–IV (Vandana et al., 2018).
Enzymatic Activation/Processing	LdMCAs has arginine/lysine specificity without any proteolytic activation LmjMCA activated by auto-processing and shows arginine/lysine substrate specificity.	Arg/Lys specificity and activity was strictly Ca2+-dependent.	Arg/Lys specificity and activity were Ca2+-independent and no auto-processing occurred in PfMCA-2 (Vandana et al., 2018). PfMCA-1 shows auto processing leading to pro-domain removal as typical of initiator caspases.
Forms/Types	All Leishmania species expressed one single metacaspase gene except L.infantum and L. donovani, in which two metacaspases were reported.	Type-I metacaspases; T. brucei has TbMCA1-TbMCA5 and T. cruzi has TcMCA3 and TcMCA5.	Type-I metacaspases; P. falciparumPfMCA1-3, P. vivax PvMCA1-3, and P. berghei (PbMCA1-3)
Predicted Functions	Predicted to be involved in stress-induced cell death regulation. LmjMCAs involved in cell cycle progression.	Regulation of cell death pathways; cytokinesis of parasite. Mechanistic role in PCD needs to be explored deeply.	PfMCA-2 is likely involved in the progression of growth in vitro and indirectly responsible for cell death in the parasite (Vandana et al., 2018). Role of other MCAs of P. vivax and P. berghei needs to be elucidated.