PROSITE documentation PDOC50168

{PDOC50168}
{PS50168; DED}
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* Death effector domain (DED) profile *
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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 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

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