Motif contained in proteins involved in apoptotic signalling. Mediates homodimerisation. Structure consists of six antiparallel helices arranged in a topology homologue to the DEATH and the DED domain.
The caspase recruitment domain (CARD domain) is a homotypic protein interaction module composed of a bundle of six alpha-helices. CARD is related in sequence and structure to the death domain (DD, see IPR000488 ) and the death effector domain (DED, see IPR001875 ), which work in similar pathways and show similar interaction properties [ (PUBMED:11504623) ]. The CARD domain typically associates with other CARD-containing proteins, forming either dimers or trimers. CARD domains can be found in isolation, or in combination with other domains. Domains associated with CARD include: NACHT ( IPR007111 ) (in Nal1 and Bir1), NB-ARC ( IPR002182 ) (in Apaf-1), pyrin/dapin domains ( IPR004020 ) (in Nal1), leucine-rich repeats ( IPR001611 ) (in Nal1), WD repeats ( IPR001680 ) (in Apaf1), Src homology domains ( IPR001452 ), PDZ ( IPR001478 ), RING, kinase and DD domains [ (PUBMED:15226512) ].
CARD-containing proteins are involved in apoptosis through their regulation of caspases that contain CARDs in their N-terminal pro-domains, including human caspases 1, 2, 9, 11 and 12 [ (PUBMED:9175472) ]. CARD-containing proteins are also involved in inflammation through their regulation of NF-kappaB [ (PUBMED:12101092) ]. The mechanisms by which CARDs activate caspases and NF-kappaB involve the assembly of multi-protein complexes, which can facilitate dimerisation or serve as scaffolds on which proteases and kinases are assembled and activated.
Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment.
Cell. 1998; 94: 171-80
Display abstract
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.
Proc Natl Acad Sci U S A. 1998; 95: 5156-60
Display abstract
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 interleukin-1 beta converting enzyme family of cysteine proteases.
J Cell Biochem. 1997; 64: 2-10
Display abstract
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.
Metabolism (metabolic pathways involving proteins which contain this domain)
Epithelial cell signaling in Helicobacter pylori infection
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with CARD domain which could be assigned to a KEGG orthologous group, and not all proteins containing CARD domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
