PROSITE documentation PDOC50168Death effector domain (DED) profile
The apoptotic signal coming from ligand-induced oligomerization of death receptors is mediated by a number of adaptor proteins containing specialized interaction domains. Besides the death effector domain (DED), this group is formed by the death domain (DD) (see <PDOC50017>) and the caspase recruitment domain (CARD) (see <PDOC50209>).
The death effector domain was first described in the FADD/Mort1 protein [1] and later shown to also occur in several other proteins [2,3]. The DED typically associates with other DED-containing proteins, forming either dimers or trimers [2,3,4]. It has been predicted that the DED is related in structure and sequence to both DD and CARD domains, which work in similar pathways and show similar interaction properties [5]. Important members of the DED family are:
- FADD/MORT1 death adaptor protein.
- Caspase-8 (EC 3.4.22.-), upstream death protease, interacts with FADD.
- Caspase-10 (EC 3.4.22.-).
- v-FLIP, FLICE(caspase)-inhibitors that occur in γ herpesviruses and the poxvirus MCV, interact with FADD and/or Caspase-8.
- c-FLIP, cellular FLICE-inhibitor with inactive caspase domain, interacts with FADD and/or caspase-8.
- PEA15, a brain-specific phosphoprotein of unknown function
The profile covers the complete domain.
Expert(s) to contact by email: Last update:December 2001 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Chinnaiyan A.M. O'Rourke K. Tewari M. Dixit V.M. |
| Title | FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. | |
| Source | Cell 81:505-512(1995). | |
| PubMed ID | 7538907 |
| 2 | Authors | Thome M. Schneider P. Hofmann K. Fickenscher H. Meinl E. Neipel F. Mattmann C. Burns K. Bodmer J.L. Schroter M. Scaffidi C. Krammer P.H. Peter M.E. Tschopp J. |
| Title | Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. | |
| Source | Nature 386:517-521(1997). | |
| PubMed ID | 9087414 |
| 3 | Authors | Irmler M. Thome M. Hahne M. Schneider P. Hofmann K. Steiner V. Bodmer J.L. Schroter M. Burns K. Mattmann C. Rimoldi D. French L.E. Tschopp J. |
| Title | Inhibition of death receptor signals by cellular FLIP. | |
| Source | Nature 388:190-195(1997). | |
| PubMed ID | 9217161 | |
| DOI | 10.1038/40657 |
| 4 | Authors | Muzio M. Chinnaiyan A.M. Kischkel F.C. O'Rourke K. Shevchenko A. Ni J. Scaffidi C. Bretz J.D. Zhang M. Gentz R. Mann M. Krammer P.H. Peter M.E. Dixit V.M. |
| Title | FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. | |
| Source | Cell 85:817-827(1996). | |
| PubMed ID | 8681377 |
| 5 | Authors | Hofmann K. Bucher P. Tschopp J. |
| Title | The CARD domain: a new apoptotic signalling motif. | |
| Source | Trends Biochem. Sci. 22:155-156(1997). | |
| PubMed ID | 9175472 |
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)