CAD

Domains present in proteins implicated in post-mortem DNA fragmentation
CAD
SMART accession number:SM00266
Description: -
Interpro abstract (IPR003508):

The CIDE-N or CAD domain is a ~78 amino acid protein-protein interaction domain in the N-terminal part of Cell death-Inducing DFF45-like Effector (CIDE) proteins, involved in apoptosis. At the final stage of programmed cell death, chromosomal DNA is degraded into fragments by Caspase-activated DNase (CAD), also named DNA fragmentation factor 40 kDa (DFF40). In normal cells CAD/DFF40 is completely inhibited by its binding to DFF45 or Inhibitor of CAD (ICAD). Apoptotic stimuli provoke cleavage of ICAD/DFF45 by caspases, resulting in self-assembly of CAD/DFF40 into the active dimer [(PUBMED:15149602)].

Both CAD/DFF40 and ICAD/DFF45 possess an N-terminal CIDE-N domain that is involved in their interaction. The name of the CIDE-N domain refers to the CIDE proteins and CAD, where the domain forms the N-terminal part [(PUBMED:9564035), (PUBMED:10619428)]. The CIDE-N domains from different proteins can interact, e.g. CIDE-N of CIDE-B and ICAD/DFF45 with CIDE-N of CAD/DFF40, and such interactions can also be needed for proper folding [(PUBMED:10764577), (PUBMED:11371636)].

Tertiary structures show that the CIDE-N domain forms an alpha/beta roll fold of five beta-strands forming a single, mixed parallel/anti-parallel beta-sheet with one [(PUBMED:10764577)] or two [(PUBMED:10619428), (PUBMED:11371636)] alpha-helices packed against the sheet. Binding surfaces of the CIDE-N domain form a central hydrophobic cluster, while specific binding interfaces can be formed by charged patches.

Some proteins known to contain a CIDE-N domain include:

  • Mammalian DNA fragmentation factor 40 kDa (DFF40) or Caspase-activated deoxyribonuclease (CAD), an endonuclease that induces DNA fragmentation and chromatin condensation during apoptosis. The degradation of chromosomal DNA by CAD/DFF40 will kill the cells.
  • Mammalian DNA fragmentation factor 45 kDa (DFF45) or Inhibitor of CAD (ICAD), which controls the activity and proper folding of CAD/DFF40.
  • Mammalian CIDE-A and CIDE-B, activators of cell death and DNA fragmentation that can be inhibited by ICAD/DFF45. In contrast with CAD and ICAD, the CIDE proteins are expressed in a highly restricted way and show pronounced tissue specificity.
  • Fruit fly DNAation factor DREP1, a DFF45 homologue that can inhibit CIDE-A-induced apoptosis.
GO process:apoptotic process (GO:0006915)
GO component:intracellular (GO:0005622)
Family alignment:
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There are 475 CAD domains in 475 proteins in SMART's nrdb database.

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