PROSITE documentation PDOC51135 [for PROSITE entry PS51135]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.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Woo E.J. Kim Y.G. Kim M.S. Han W.D. Shin S. Robinson H. Park S.Y. Oh B.H. |
| Title | Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway. | |
| Source | Mol. Cell 14:531-539(2004). | |
| PubMed ID | 15149602 |
| 2 | Authors | Inohara N. Koseki T. Chen S. Wu X. Nunez G. |
| Title | CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. | |
| Source | EMBO J. 17:2526-2533(1998). | |
| PubMed ID | 9564035 | |
| DOI | 10.1093/emboj/17.9.2526 |
| 3 | Authors | Lugovskoy A.A. Zhou P. Chou J.J. McCarty J.S. Li P. Wagner G. |
| Title | Solution 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. | |
| Source | Cell 99:747-755(1999). | |
| PubMed ID | 10619428 |
| 4 | Authors | Uegaki K. Otomo T. Sakahira H. Shimizu M. Yumoto N. Kyogoku Y. Nagata S. Yamazaki T. |
| Title | Structure of the CAD domain of caspase-activated DNase and interaction with the CAD domain of its inhibitor. | |
| Source | J. Mol. Biol. 297:1121-1128(2000). | |
| PubMed ID | 10764577 | |
| DOI | 10.1006/jmbi.2000.3643 |
| 5 | Authors | Zhou P. Lugovskoy A.A. McCarty J.S. Li P. Wagner G. |
| Title | Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001). | |
| PubMed ID | 11371636 | |
| DOI | 10.1073/pnas.111145098 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)