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29  structures 383  species 0  interactions 1898  sequences 29  architectures

Family: CIDE-N (PF02017)

Summary: CIDE-N domain

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CIDE-N domain Provide feedback

This domain is found in CAD nuclease O76075 , ICAD O00273 the inhibitor of CAD nuclease. The two proteins interact through this domain.

Literature references

  1. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S; , Nature 1998;391:43-50.: A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [see comments] [published erratum appears in Nature 1998 May 28;393(6683):396] PUBMED:9422506 EPMC:9422506

  2. Sakahira H, Enari M, Nagata S; , Nature 1998;391:96-99.: Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis [see comments] PUBMED:9422513 EPMC:9422513

  3. Lugovskoy AA, Zhou P, Chou JJ, McCarty JS, Li P, Wagner G; , Cell 1999;99:747-755.: 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 [In Process Citation] PUBMED:10619428 EPMC:10619428

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry 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 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 [ 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 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.

Gene Ontology

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Domain organisation

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Seed source: [3]
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 85
Number in full: 1898
Average length of the domain: 73.10 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 25.31 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.6 23.9
Noise cut-off 23.3 23.4
Model length: 77
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CIDE-N domain has been found. There are 29 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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