{PDOC51135}
{PS51135; CIDE_N}
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* CIDE-N domain profile *
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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 alpha/beta roll fold
of five beta-strands forming a single, mixed parallel/anti-parallel beta-sheet
with  one  [4]  or  two  [3,5]  alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: June 2005 / First entry.

[ 1] Woo E.J., Kim Y.G., Kim M.S., Han W.D., Shin S., Robinson H.,
     Park S.Y., Oh B.H.
     "Structural mechanism for inactivation and activation of CAD/DFF40 in
     the apoptotic pathway."
     Mol. Cell 14:531-539(2004).
     PubMed=15149602
[ 2] Inohara N., Koseki T., Chen S., Wu X., Nunez G.
     "CIDE, a novel family of cell death activators with homology to the 45
     kDa subunit of the DNA fragmentation factor."
     EMBO J. 17:2526-2533(1998).
     PubMed=9564035; DOI=10.1093/emboj/17.9.2526
[ 3] Lugovskoy A.A., Zhou P., Chou J.J., McCarty J.S., Li P., Wagner G.
     "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."
     Cell 99:747-755(1999).
     PubMed=10619428
[ 4] Uegaki K., Otomo T., Sakahira H., Shimizu M., Yumoto N., Kyogoku Y.,
     Nagata S., Yamazaki T.
     "Structure of the CAD domain of caspase-activated DNase and
     interaction with the CAD domain of its inhibitor."
     J. Mol. Biol. 297:1121-1128(2000).
     PubMed=10764577; DOI=10.1006/jmbi.2000.3643
[ 5] Zhou P., Lugovskoy A.A., McCarty J.S., Li P., Wagner G.
     "Solution structure of DFF40 and DFF45 N-terminal domain complex and
     mutual chaperone activity of DFF40 and DFF45."
     Proc. Natl. Acad. Sci. U.S.A. 98:6051-6055(2001).
     PubMed=11371636; DOI=10.1073/pnas.111145098

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