|PROSITE documentation PDOC50017 [for PROSITE entry PS50017]|
The death domain [1,2,3] (FAS/TNF cytosolic interaction domain) has first been described as a region in the cytoplasmic tail of the 75 Kd TNF receptor (TNFR-1) (see <PDOC00561>) which is involved in TNF-mediated cell death signaling. A corresponding region is found in the cytoplasmic tail of FAS/APO1 another surface receptor inducing apoptotic cell death. This region mediates self-association of these receptors, thus giving the signal to downstream events leading to apoptosis.
Subsequently, a number of other proteins have been found to interact with the cytoplasmic part of either FAS or the TNF receptor in the region of the death domain. Overexpression of these proteins usually leads to cell death. By profile analysis, it has been shown that a number of other proteins contain regions with significant similarity to the death domain. Interestingly, several of these proteins also work in the context of cell death signaling.
The following proteins have been found to contain a death domain:
In most of these proteins, the death domain is located at the extreme C-terminus. Exceptions are ankyrin, MyD88 and pelle, all protein probably not directly involved in cell death signaling. In the case of ankyrin, the isoform 2.1 is a splice variant which has the death domain located at the C-terminus.
The profile covers the complete domain up to the boundaries that define a minimally functional death domain in FAS and TNF-receptor. This region is slightly bigger than the observed sequence conservation.Expert(s) to contact by email:
July 1999 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Cleveland J.L. Ihle J.N.|
|Title||Contenders in FasL/TNF death signaling.|
|2||Authors||Hofmann K. Tschopp J.|
|Title||The death domain motif found in Fas (Apo-1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance.|
|Source||FEBS Lett. 371:321-323(1995).|
|3||Authors||Feinstein E. Kimchi A. Wallach D. Boldin M. Varfolomeev E.|
|Title||The death domain: a module shared by proteins with diverse cellular functions.|
|Source||Trends Biochem. Sci. 20:342-344(1995).|
|4||Authors||Golstein P. Marguet D. Depraetere V.|
|Title||Homology between reaper and the cell death domains of Fas and TNFR1.|