|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6y2x' size='340' side='right'caption='[[6y2x]], [[Resolution|resolution]] 1.77Å' scene=''> | | <StructureSection load='6y2x' size='340' side='right'caption='[[6y2x]], [[Resolution|resolution]] 1.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6y2x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y2X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y2X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6y2x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y2X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[62yy|62yy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DTX2, KIAA1528, RNF58 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6y2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y2x OCA], [https://pdbe.org/6y2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y2x RCSB], [https://www.ebi.ac.uk/pdbsum/6y2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y2x ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y2x OCA], [http://pdbe.org/6y2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y2x RCSB], [http://www.ebi.ac.uk/pdbsum/6y2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y2x ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DTX2_HUMAN DTX2_HUMAN]] Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. | + | [https://www.uniprot.org/uniprot/DTX2_HUMAN DTX2_HUMAN] Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RING-type E3 ubiquitin transferase]]
| + | [[Category: Buetow L]] |
| - | [[Category: Buetow, L]] | + | [[Category: Gabrielsen M]] |
| - | [[Category: Gabrielsen, M]] | + | [[Category: Huang DT]] |
| - | [[Category: Huang, D T]] | + | |
| - | [[Category: E3 ring ligase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Par-binding]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| Structural highlights
Function
DTX2_HUMAN Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.
Publication Abstract from PubMed
Cross-talk between ubiquitination and ADP-ribosylation regulates spatiotemporal recruitment of key players in many signaling pathways. The DELTEX family ubiquitin ligases (DTX1 to DTX4 and DTX3L) are characterized by a RING domain followed by a C-terminal domain (DTC) of hitherto unknown function. Here, we use two label-free mass spectrometry techniques to investigate the interactome and ubiquitinated substrates of human DTX2 and identify a large proportion of proteins associated with the DNA damage repair pathway. We show that DTX2-catalyzed ubiquitination of these interacting proteins requires PARP1/2-mediated ADP-ribosylation and depends on the DTC domain. Using a combination of structural, biochemical, and cell-based techniques, we show that the DTX2 DTC domain harbors an ADP-ribose-binding pocket and recruits poly-ADP-ribose (PAR)-modified proteins for ubiquitination. This PAR-binding property of DTC domain is conserved across the DELTEX family E3s. These findings uncover a new ADP-ribose-binding domain that facilitates PAR-dependent ubiquitination.
DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination.,Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT Sci Adv. 2020 Aug 21;6(34). pii: 6/34/eabc0629. doi: 10.1126/sciadv.abc0629., Print 2020 Aug. PMID:32937373[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT. DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination. Sci Adv. 2020 Aug 21;6(34). pii: 6/34/eabc0629. doi: 10.1126/sciadv.abc0629., Print 2020 Aug. PMID:32937373 doi:http://dx.doi.org/10.1126/sciadv.abc0629
|
