RING finger, H2 subclass, found in E3 ubiquitin-protein ligase Deltex1 (DTX1), Deltex2 (DTX2), Deltex4 (DTX4), and similar proteins
This family includes Drosophila melanogaster Deltex, its vertebrate homologs, DTX1, DTX2, and DTX4, and other similar proteins mainly from eumetazoa. Deltex is a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus. The vertebrate homologs of Deltex have been involved in Notch signaling and neurogenesis. The mammalian DTX1 is most closely related to the Drosophila Deltex. Both of them bind to SH3-domain containing protein Grb2 and further inhibit E2A. DTX1 functions as a Notch downstream transcription regulator. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participated in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1. So it likely interacts with the intracellular domain of Notch as well. Like DTX1 and DTX4, DTX2 is expressed in thymocytes. It interacts with the intracellular domain of Notch receptors and acts as a negative regulator of Notch signals in T cells. However, the endogenous levels of DTX1 and DTX2 is not important for regulating Notch signals during thymocyte development. In contrast to other DTXs, DTX3 does not contain N-terminal two Notch-binding WWE domains, but a short unique N-terminal domain. It does not interact with intracellular domain of Notch. In addition, it has a different class of RING finger (C3HC4 type or RING-HC subclass) than do the other DTXs which harbor a C3H2C3-type RING-H2 finger. Thus DTX3 is not included in this family.