DDB G0282499

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Transcriptional modulators of the E2F family fall into two groups. Both groups have othologs in animals and plants and thus appear to be ancient. One of these groups is well known and the other less so.

The better known group, represented by animal E2F1-3 and E2Fs a, b and c of Arabidopsis, consists of proteins which form heterodimers with the "dimerization partner", DP. E2F and DP each contribute half of the DNA binding motif of the dimer. E2F proteins in this group have a single DNA binding domain and a leucine-zipper motif which mediates the E2F/DP interaction; there is also a transactivation domain and domain for interaction with the retinoblastoma susceptibility protein Rb. In animals, further members of this group are found which have lost the transactivation domain, and appear to function as transcriptional repressors; examples are E2F4-6[1].

Proteins in the second group, which includes animal E2F7-8 and DEL1-3 of Arabidopsis, are thought to act as monomers. These proteins contain two DNA binding domains, each of which is identifiable by its homology to the DNA binding domain of E2F. These proteins lack activation domains and are thought to act as repressors. Proteins of this group were discovered relatively recently; their roles appear to include proliferation control but are not limited to this [2].

Blast searches in D. discoideum turn up one heterodimeric E2F protein (DDB_G0284129) but none in the second group. However, when the search universe is extended to include other cellular slime molds, good orthologs of monomeric E2Fs are recovered from Polysphondylium and D. fasciculatum. When these are blasted into Dd, they hit DDB_G0271994 and DDB_G0282499 with respectable e-values. The Dd proteins appear to be highly diverged, so that the E2F binding domains are barely recognizable, if at all. When they are blasted back to the human proteome, the first hits are nonetheless to E2F7, albeit at marginal e-value. Tree-building algorithms support the idea that these proteins belong in in the monomeric E2F group.

Harry MacWilliams, February 2011

Image:E2f family conserved domains.tif

Image:e2f family tree.tif

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