Domain

CIDE-N domain (IPR003508)

Short name: CIDE-N_dom

Overlapping homologous superfamilies

None.

Domain relationships

None.

Description

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 40kDa (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 [PMID: 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 [PMID: 9564035, PMID: 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 [PMID: 10764577, PMID: 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 [PMID: 10764577] or two [PMID: 10619428, PMID: 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 40kDa (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 45kDa (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 terms

Biological Process

GO:0006915 apoptotic process

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles
Pfam
SMART