Conserved Protein Domain Family

cd16459: RING-H2_DTX1_like 
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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.
PSSM-Id: 319373
View PSSM: cd16459
Aligned: 13 rows
Threshold Bit Score: 65.1019
Threshold Setting Gi: 765548404
Created: 2-May-2013
Updated: 18-Aug-2016
Aligned Rows:
Zn binding siteRING-H2 finger
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:Zn binding site [ion binding site]
  • Structure:1V87; Mus musculus Deltex2 binding two Zn2+ ions through its RING-H2 finger.
    View structure with Cn3D

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70
Feature 1         #  #                               # #  #  #                    #  #     
1V87_A        27 DCIICMEKLAvasgysdmt--dskalgpmvVGRLTKCSHAFHLLCLLAMYcng-----nkDGSLQCPSCKTIYG 93
gi 260799660 379 DCPICCENLRgpsgydat-----dnmapsmVTKLQHCNHVFHGVCLLAMYnsg-----skDGSLQCPSCKTIYG 442
gi 405964812 391 DCCICCEKLThasgyge------gkkdekvVFKLNRCSHMFHKLCILAMYest-----tkNGSVQCPTCKTIYG 453
gi 37077046  410 DCTICMERLVtasgyegvl--rhkgvrpelVGRLGRCGHMYHLLCLVAMYsng-----nkDGSLQCPTCKAIYG 476
gi 585664949   1 DCPICFEELCsnsgyee-------nkassvVYKLDKCGHVFHKSCLAAMYnsg-----pkDGSLQCPTCKAIYG 62
gi 919045669 396 DCCICCEKLNdasgyd---------skdtvVFQLRKCSHMFHKACLHAMYeng-----qkDGSIQCPTCKTIYG 455
gi 780113393 429 ECPICFEKLCnvshyne------deeegdsVLKLDRCRHFFHQSCLYAMYnsg-----pkDGSIQCPTCKAIYG 491
gi 70569222  320 DCVICMTSLSdvsgfqts----gatnqassVIELKTCKHIFHAECLIASMqs------gaNDSFTCPCCKVIYG 383
gi 443732723 401 ECPICCADLKsasgfceg-----asgghpaVIQLKRCKHAYHTDCMVAMYens-----akNGCLQCPTCKTIYG 464
gi 215497426 225 DCSICREPLCqpsay----------agsgrVVRLRRCSHPLHHACLVAMCqss-----pqAGHLQCPVCKALHG 283
gi 156214891   1 ECAICIEKLSevsgfcqt-----asstlpeVKKLTKCNHCFHEECLLELLkn------skGGYIQCPTCKTIHG 63
gi 340381924 234 PCPICMNNLNeesgfeddstpspsstsscdVCKLRKCGHMLHRSCLITYSkns----tdaKGCLRCPTCKVIHG 303
gi 765548404 456 DCSLCYAEPLaq-----------------aPCIRNACGHVFHHACLVQQIsaghsgkrivFTYLKCPQCPKLIS 512

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