PROSITE documentation PDOC51135
CIDE-N domain profile


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 [1].

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 [2,3]. 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 [4,5].

Tertiary structures show that the CIDE-N domain forms an α/β roll fold of five β-strands forming a single, mixed parallel/anti-parallel β-sheet with one [4] or two [3,5] α-helices packed against the sheet (see <PDB:1IBX>). 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:

  • 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 homolog that can inhibit CIDE-A-induced apoptosis.

The profile we developed covers the entire CIDE-N domain.

Last update:

June 2005 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CIDE_N, PS51135; CIDE-N domain profile  (MATRIX)


1AuthorsWoo E.J. Kim Y.G. Kim M.S. Han W.D. Shin S. Robinson H. Park S.Y. Oh B.H.
TitleStructural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway.
SourceMol. Cell 14:531-539(2004).
PubMed ID15149602

2AuthorsInohara N. Koseki T. Chen S. Wu X. Nunez G.
TitleCIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor.
SourceEMBO J. 17:2526-2533(1998).
PubMed ID9564035

3AuthorsLugovskoy A.A. Zhou P. Chou J.J. McCarty J.S. Li P. Wagner G.
TitleSolution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis.
SourceCell 99:747-755(1999).
PubMed ID10619428

4AuthorsUegaki K. Otomo T. Sakahira H. Shimizu M. Yumoto N. Kyogoku Y. Nagata S. Yamazaki T.
TitleStructure of the CAD domain of caspase-activated DNase and interaction with the CAD domain of its inhibitor.
SourceJ. Mol. Biol. 297:1121-1128(2000).
PubMed ID10764577

5AuthorsZhou P. Lugovskoy A.A. McCarty J.S. Li P. Wagner G.
TitleSolution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45.
SourceProc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001).
PubMed ID11371636

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