Family C14

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

C14A

Summary Holotypes Alignment Tree Genomes Literature

C14B

Summary Holotypes Alignment Tree Genomes Literature

Summary for family C14

NamePeptidase family C14 (caspase family)
Family type peptidaseC14.001 - caspase-1 (Rattus norvegicus), MEROPS Accession MER0000852 (peptidase unit: 119-402)
Content of familyPeptidase family C14 contains cytosolic endopeptidases termed caspases that have strict specificity for the hydrolysis of aspartyl bonds.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeCysteine
Active siteThe 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 specificitiesAll the peptidases of family C14 have a strict requirement for the amino acid in P1 to be aspartate. However, the substrate specificities of the individual caspases are distinct, being determined by the residues present in the pockets of P2, P3 and P4.
InhibitorsCaspase-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 structureThe 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 & Grütter, 2002) known as the Rossmann fold. The active enzyme has been shown to be a dimer.
ClanCD
Basis of clan assignmentType family of clan CD.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsThe 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 relevanceCaspase inhibitors have potential for the treatment of problems caused by excessive apoptosis. These include ischaemic damage and neurodegenerative diseases.
Statistics for family C14Sequences:6109
Identifiers:59
Identifiers with PDB entries:15
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily C14A
Name Peptidase subfamily C14A
Subfamily type peptidase C14.001 - caspase-1 (Rattus norvegicus), MEROPS Accession MER0000852 (peptidase unit: 119-402)
Active site residues H236 C284 
Statistics Sequences: 4085
Identifiers: 40
Identifiers with PDB entries: 11
Other databases CATH 3.40.50.1460
HOMSTRAD CASc
HSSP 1ice
INTERPRO IPR002398
PANTHER PTHR10454
PFAM PF00656
SCOP 52130
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
caspase-1C14.001-
CED-3 peptidaseC14.002Yes
caspase-3C14.003Yes
caspase-7C14.004Yes
caspase-6C14.005Yes
caspase-2C14.006Yes
caspase-4C14.007-
caspase-5C14.008-
caspase-8C14.009Yes
caspase-9C14.010Yes
caspase-10C14.011-
caspase-11C14.012-
caspase-12C14.013-
caspase CSP-2 (Caenorhabditis elegans)C14.014-
caspase (insect 1)C14.015Yes
caspase (insect 2)C14.016-
caspase-13C14.017-
caspase-14C14.018-
caspase DRONC (Drosophila melanogaster)-type peptidaseC14.019Yes
caspase DECAYC14.022-
caspase STRICA (Drosophila sp.)C14.023-
Mername-AA065 peptidaseC14.024-
caspase DAMM (Drosophila sp.)C14.025-
Mername-AA143 peptidaseC14.028-
Mername-AA186 peptidaseC14.029-
Caspy peptidase (Brachydanio rerio-type)C14.030-
Caspy2 g.p. (Brachydanio rerio)C14.031-
SfAV caspase (Spodoptera frugiperda ascovirus)C14.037-
caspase-15C14.038-
caspase DreddC14.040-
caspase PmCasp (Penaeus monodon)-like peptidaseC14.042-
FLIP proteinC14.971Yes
CASH-alpha (Mus musculus)C14.974-
Mername-AA142 proteinC14.976-
protein similar to ICE-like cysteine peptidase (Rattus norvegicus)C14.977-
metacaspase-1 (Plasmodium sp.)C14.978-
csp-1 g.p. (Caenorhabditis elegans)C14.A06-
CASc g.p. (Brachydanio rerio)C14.A08-
caspase-12 pseudogene (Homo sapiens)C14.P01-
Mername-AA093 caspase pseudogeneC14.P02-
subfamily C14A non-peptidase homologuesnon-peptidase homologue-
subfamily C14A unassigned peptidasesunassignedYes
Subfamily C14B
Name Peptidase subfamily C14B
Subfamily type peptidase C14.035 - metacaspase Yca1 ({Saccharomyces cerevisiae}-type) (Saccharomyces cerevisiae), MEROPS Accession MER0039482 (peptidase unit: 135-329)
Active site residues H220 C276 
Statistics Sequences: 1940
Identifiers: 19
Identifiers with PDB entries: 4
Other databases INTERPRO IPR002398
PANTHER PTHR31773
PFAM PF00656
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
paracaspaseC14.026Yes
metacaspase-4 (Arabidopsis-type)C14.033-
metacaspase-9 (Arabidopsis-type)C14.034-
metacaspase Yca1 (Saccharomyces cerevisiae-type)C14.035Yes
metacaspase mcII-Pa (Picea abies)-like peptidaseC14.036-
metacaspase PfMCA1 (Plasmodium falciparum)-like peptidaseC14.041-
metacaspase Ld (Leishmania-type)C14.043-
metacaspase TbMCA2C14.044Yes
metacaspase Ac (Acanthamoeba-type)C14.045-
metacaspase Atmc8 (Arabidopsis thaliana)C14.046-
metacaspase-1 (Arabidopsis-type)C14.047-
bacterial metacaspaseC14.048Yes
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 homologuesnon-peptidase homologue-
subfamily C14B unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
family C14 non-peptidase homologuesnon-peptidase homologue-
family C14 unassigned peptidasesunassigned-