Fig. 7

Schematic comparison of the domain architecture of the DTX family. Domain architecture of the human Deltex-like E3 ubiquitin ligases and DTX family members DTX1, DTX2A, DTX2B, DTX3, DTX3L and DTX4. The domain organization is based on analogous functional motifs in murine DTX family members DTX1, DTX2, DTX2deltaE and DTX3 [589], human DTX1 [544, 646], and human DTX3L [542, 543]. DTX1, DTX2 and DTX4 have well-conserved domains I, II and III. DTX1, DTX2A, DTX2B and DTX4 contain two conserved tandem WWE modules in their domain I [646]. The N-terminal domains I of DTX1, DTX2A and DTX2B bind through their tandem WWE modules to the ankyrin repeat region of intracellular NOTCH1 [646]. The WWE domain is named after three conserved residues (W-W-E)and is predicted to mediate specific protein-protein interactions in ubiquitin- and ADP-ribose conjugation systems [555, 636, 637]. DTX3 lacks most of the site corresponding to the binding site for the ankyrin repeats of human NOTCH1. Of interest, the WWE domain of DTX1 serves also as a bona fide poly-ADP-ribose binding module [555]. Domains II of DTX1, DTX2A, DTX3 and DTX4 contain a proline-rich region (black boxes) that is not found in DTX3L. DTX2B is an alternatively spliced form of DTX2A, DTX2B lack a proline-rich motif (PRM), the fourth of nine predicted DTX2 exons. The most conserved region of all human DTX family members (DTX1, DTX2A, DTX2B, DTX3, DTX3L and DTX4) is their C-terminal part, domain III. The C-terminal domain III of DTX1, DTX2A, DTX2B and DTX4 contain a classic RING finger E3 ubiquitin ligase domain (RING-H2 finger motif; red box); while domain III of DTX3 and DTX3L contain a RING-C3HC4 finger motif found in many E3 ubiquitin ligases (indicated by an orange box). Human DTX3 has a short unique N-terminal domain (yellow box), and DTX3L contains a longer unique N-terminal region (grey box). Abbreviations: RING really interesting new gene, DTX deltex, DTC Deltex C-terminal domain