Table 1.

Comparative analysis of key properties of caspases, metacaspases, and paracaspases.

Properties	Caspases	Metacaspases	Paracaspases	Reference
Distribution	Metazoans	Protists, fungi, algae, and plants	Metazoans and Dictyostelium	Uren et al. (2000)
Catalytic site	His-Cys catalytic dyad	His-Cys catalytic dyad with few exceptions such as TbMCA-1 and TbMCA-4 that have Tyr and Ser in place of His-Cys.	His-Cys catalytic dyad	Uren et al. (2000); Hachmann et al. (2012); McLuskey and Mottram (2015)
Substrate specificity	Aspartic acid specificity	Arginine and lysine substrate specificity	Arginine-specific protease	Uren et al. (2000); Hachmann et al. (2012)
Types/forms	Effectors caspases (caspase-2, -3, -6, -7) and initiator caspases (caspase-8, -9, -10)	Type-I metacaspases have N-terminal pro-domain with proline-rich repeat motif and zinc finger motif. Type II metacaspases lack pro-domain but possess a linker region between the large (p20) and small (p10) subunits. Type III metacaspases found only in algae that have undergone secondary endosymbiosis	Type-1 paracaspases constitute MALT1-like domain having death domain, immunoglobulin-like domains and a caspase-like domain. Type-II paracaspases in metazoan represent ancestral form, having caspase-like-domain.	Uren et al. (2000); Mottram et al. (2003); Elmore (2007); Hulpiau et al. (2016)
Biological functions	Key regulators of programmed cell death, proliferation and inflammation, playing essential roles in the survival and death of animal cells.	Multifunctional proteases essential for parasite physiology but their detailed functions were poorly characterized.	Plays a major role in several pro-inflammatory pathways in innate and adaptive immunity.	Nuñez et al. (1998) Elmore (2007)
Enzymatic functions	Endo-proteases- hydrolyze peptide bonds that depend on catalytic cysteine residue in the active site and occur after aspartic acid residue in the substrates. Caspase-mediated processing results in substrate inactivation. It may also generate active signaling molecules that participate in ordered processes such as apoptosis and inflammation.	Cysteine proteases hydrolyze peptide bonds after arginine/lysine residues in their substrates Report on T. brucei MCA-4 suggested that the phenotypes induced by TbMCA-4 expression in yeast were completely lost when the putative catalytic dyad residues histidine164 and cystein218 were both independently mutated to alanine.	Cysteine proteases hydrolyze peptide bonds after arginine residues in their substrates	1. Uren et al. (2000); Szallies et al. (2002); McIlwain et al. (2013)