Taxonomic distribution of proteins containing CARD domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing CARD domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment.

Chou JJ, Matsuo H, Duan H, Wagner G
Cell. 1998; 94: 171-80

Apoptosis requires recruitment of caspases by receptor-associated adaptors through homophilic interactions between the CARDs (caspase recruitment domains) of adaptor proteins and prodomains of caspases. We have solved the CARD structure of the RAIDD adaptor protein that recruits ICH-1/caspase-2. It consists of six tightly packed helices arranged in a topology homologous to the Fas death domain. The surface contains a basic and an acidic patch on opposite sides. This polarity is conserved in the ICH-1 CARD as indicated by homology modeling. Mutagenesis data suggest that these patches mediate CARD/CARD interaction between RAIDD and ICH-1. Subsequent modeling of the CARDs of Apaf-1 and caspase-9, as well as Ced-4 and Ced-3, showed that the basic/acidic surface polarity is highly conserved, suggesting a general mode for CARD/CARD interaction.

ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases.

Koseki T, Inohara N, Chen S, Nunez G
Proc Natl Acad Sci U S A. 1998; 95: 5156-60

We have identified and characterized ARC, apoptosis repressor with caspase recruitment domain (CARD). Sequence analysis revealed that ARC contains an N-terminal CARD fused to a C-terminal region rich in proline/glutamic acid residues. The CARD domain of ARC exhibited significant homology to the prodomains of apical caspases and the CARDs present in the cell death regulators Apaf-1 and RAIDD. Immunoprecipitation analysis revealed that ARC interacts with caspase-2, -8, and Caenorhabditis elegans CED-3, but not with caspase-1, -3, or -9. ARC inhibited apoptosis induced by caspase-8 and CED-3 but not that mediated by caspase-9. Further analysis showed that the enzymatic activity of caspase-8 was inhibited by ARC in 293T cells. Consistent with the inhibition of caspase-8, ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis factor-R1, and TRAMP/DR3. Remarkably, the expression of human ARC was primarily restricted to skeletal muscle and cardiac tissue. Thus, ARC represents an inhibitor of apoptosis expressed in muscle that appears to selectively target caspases. Delivery of ARC by gene transfer or enhancement of its endogenous activity may provide a strategy for the treatment of diseases that are characterized by inappropriately increased cell death in muscle tissue.

The CARD domain: a new apoptotic signalling motif.

Hofmann K, Bucher P, Tschopp J
Trends Biochem Sci. 1997; 22: 155-6

The interleukin-1 beta converting enzyme family of cysteine proteases.

Miller DK, Myerson J, Becker JW
J Cell Biochem. 1997; 64: 2-10

Interleukin-1 beta converting enzyme (ICE) is the first enzyme of a new family of cysteine endoproteinases to be isolated and characterized. An overview of the structure and activity of ICE is outlined together with highlights of salient features common to members of each of the family members.