InterPro domain: IPR029030

This superfamily represents the caspase-like domain found in caspases, metacaspases and peptidases of the C25 family (gingipains).

Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases [ 1 ]. They are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. Caspases are mainly involved in mediating cell death (apoptosis) [ 2 , 3 , 4 ]. They have two main roles within the apoptosis cascade: as initiators that trigger the cell death process, and as effectors of the process itself. Caspases can have roles other than in apoptosis, such as caspase-1 (interleukin-1 beta convertase) ( 3.4.22.36 ), which is involved in the inflammatory process. The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. Caspases may also be involved in cell differentiation [ 5 ].

Metacaspases are arginine/lysine-specific, in contrast to caspases, which are aspartate-specific. They are found only in plants [ 6 , 7 ], fungi [ 8 ] and lower eukaryotes, including the protozoa [ 9 ]. While plant metacaspases have been shown to be involved in cell death pathways, in other organisms they have evolved alternative functions [ 10 ].

Lys-gingipains are cysteine proteinases with a strong preference for substrates with Lys in the P1 position [ 11 ].

1. Evolutionary lines of cysteine peptidases. Biol. Chem. 382, 727-33
2. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6, 1028-42
3. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 68, 383-424
4. Caspase activation - stepping on the gas or releasing the brakes? Lessons from humans and flies. Oncogene 23, 2774-84
5. Death without caspases, caspases without death. Trends Cell Biol. 14, 184-93
6. Metacaspase-8 modulates programmed cell death induced by ultraviolet light and H2O2 in Arabidopsis. J. Biol. Chem. 1783, 1320-7
7. A pepper (Capsicum annuum L.) metacaspase 9 (Camc9) plays a role in pathogen-induced cell death in plants. Mol. Plant Pathol. 283, 774-83
8. Caspase-dependent apoptosis in yeast. Biochim. Biophys. Acta 286, 39914-25
9. Substrate specificity and the effect of calcium on Trypanosoma brucei metacaspase 2. FEBS J. 385, 1041-7
10. Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor. J. Biol. Chem.
11. Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes. Biol. Chem.