Family C14
Summary for family C14
| Name | Peptidase family C14 (caspase family) |
|---|
| Family type peptidase | C14.001 - caspase-1 (Rattus norvegicus), MEROPS Accession MER0000852 (peptidase unit: 119-402) |
| Content of family | Peptidase family C14 contains cytosolic endopeptidases termed caspases that have strict specificity for the hydrolysis of aspartyl, arginyl or lysyl bonds. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Cysteine |
| Active site | The active site residues are in the order His, Cys forming the catalytic dyad. Both active site residues are preceded by blocks of hydrophobic residues. The catalytic residues are found in the motifs His-Gly and Ala-Cys. These motifs are conserved throughout clan CD (Chen et al., 1998). |
| Activities and specificities | All the peptidases of family C14 have a strict requirement for the amino acid in P1. Members of subfamily C14A (caspases) have a strict specificity for aspartyl bonds. However, the substrate specificities of the individual caspases are distinct, being determined by the residues present in the pockets of P2, P3 and P4. Members of subfamily C14B (metacaspases and paracaspases) have a strict specificity for either arginyl or lysyl bonds. |
| Inhibitors | Caspase-1 is inhibited by CrmA (I04.028), a natural inhibitor from cowpox virus. Members of clan CD are known to be susceptible to peptide aldehyde and peptidylchloromethane inhibitors. Like other peptidases in clan CD, the peptidases of family C14 are not inhibited by compound E-64. |
| Molecular structure | The caspases normally exist as inactive single chain proenzymes. When cells enter apoptosis, the caspases are activated by cleavages on the carboxyl side of specific aspartic acid residues resulting in the liberation of a large (alpha) subunit and small (beta) subunit. Each alpha/beta subunit consists of five parallel and one anti-parallel beta-strands, forming a twisted beta sheet. The beta sheet is flanked by two alpha-helices on one side and three on the other (Donepudi & Grtter, 2002) known as the Rossmann fold. The active enzyme has been shown to be a dimer. Metacaspase 4 (C14.033) is also activated by self-cleavage, but this is calcium dependent (Zhu et al., 2020). |
| Clan | CD |
| Basis of clan assignment | Type family of clan CD. |
| Biological functions | The apoptosis cascade, known mainly in animal cells, is primarily controlled by the caspases. It is thought that the caspases with long prodomains are responsible for the initiation of the apoptotic response whereas those with shorter prodomains are "effector" caspases (Earnshaw et al., 1999). The effector caspases are activated by the initiator caspases and are directly responsible for cell death (Thornberry & Lazebnik, 1998). Caspase-1, the type example of family C14, is involved in the processing of interleukin 1 beta precursor and does not have a role in apoptosis. |
| Pharmaceutical and biotech relevance | Caspase inhibitors have potential for the treatment of problems caused by excessive apoptosis. These include ischaemic damage and neurodegenerative diseases. |
| Statistics for family C14 | Sequences: | 9177 |
| Identifiers: | 60 |
| Identifiers with PDB entries: | 17 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| paracaspase | C14.026 | Yes |
| metacaspase-4 (Arabidopsis-type) | C14.033 | Yes |
| metacaspase-9 (Arabidopsis-type) | C14.034 | - |
| metacaspase Yca1 (Saccharomyces cerevisiae-type) | C14.035 | Yes |
| metacaspase mcII-Pa (Picea abies)-like peptidase | C14.036 | - |
| metacaspase PfMCA1 (Plasmodium falciparum)-like peptidase | C14.041 | - |
| metacaspase Ld (Leishmania-type) | C14.043 | - |
| metacaspase TbMCA2 | C14.044 | Yes |
| metacaspase Ac (Acanthamoeba-type) | C14.045 | - |
| metacaspase Atmc8 (Arabidopsis thaliana) | C14.046 | - |
| metacaspase-1 (Arabidopsis-type) | C14.047 | - |
| bacterial metacaspase | C14.048 | Yes |
| metacaspase Atmc5 (Arabidopsis sp.) | C14.049 | - |
| orthocaspase MaOC1 (Microcystis aeruginosa) | C14.050 | - |
| metacaspase Atmc6 (Arabidopsis thaliana) | C14.A01 | - |
| metacaspase Atmc7 g.p. (Arabidopsis thaliana) | C14.A03 | - |
| metacaspase Atmc2 (Arabidopsis thaliana) | C14.A04 | - |
| metacaspase Atmc3 (Arabidopsis thaliana) | C14.A05 | - |
| pcp (Dictyostelium discoideum) | C14.A07 | - |
| Subfamily C14B non-peptidase homologues | non-peptidase homologue | - |
| Subfamily C14B unassigned peptidases | unassigned | - |
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Peptidases not assigned to subfamily
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