{PDOC50168} {PS50168; DED} {BEGIN} *************************************** * Death 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 ) and the caspase recruitment domain (CARD) (see ). 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 gamma 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 -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: The profile covers the complete domain. -Expert(s) to contact by email: Hofmann K.; Kay.Hofmann@memorec.com -Last update: December 2001 / First entry. [ 1] Chinnaiyan A.M., O'Rourke K., Tewari M., Dixit V.M. "FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis." Cell 81:505-512(1995). PubMed=7538907 [ 2] 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. "Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors." Nature 386:517-521(1997). PubMed=9087414 [ 3] 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. "Inhibition of death receptor signals by cellular FLIP." Nature 388:190-195(1997). PubMed=9217161; DOI=10.1038/40657 [ 4] 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. "FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex." Cell 85:817-827(1996). PubMed=8681377 [ 5] Hofmann K., Bucher P., Tschopp J. "The CARD domain: a new apoptotic signalling motif." Trends Biochem. Sci. 22:155-156(1997). PubMed=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 https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}