View source for 6cf6


==RNF146 TBM-Tankyrase ARC2-3 complex==
<StructureSection load='6cf6' size='340' side='right'caption='[[6cf6]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cf6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CF6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</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=6cf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cf6 OCA], [https://pdbe.org/6cf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cf6 RCSB], [https://www.ebi.ac.uk/pdbsum/6cf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cf6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TNKS1_MOUSE TNKS1_MOUSE] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1 (By similarity).
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== Publication Abstract from PubMed ==
Poly(ADP-ribosyl)ation (PARylation) catalyzed by the tankyrase enzymes (Tankyrase-1 and -2; a.k.a. PARP-5a and -5b) is involved in mitosis, telomere length regulation, GLUT-4 vesicle transport, and cell growth and differentiation. Together with the E3 ubiquitin ligase RNF146 (a.k.a. Iduna), tankyrases regulate the cellular concentrations of several important proteins including Axin, 3BP2, and angiomotins, which are key regulators of Wnt, Src and hippo signaling, respectively. These substrates of tankyrases are first PARylated and then ubiquitylated by RNF146, which is allosterically activated by binding to PAR polymer. Each tankyrase substrate is recognized by a tankyrase-binding motif (TBM). Here we show that RNF146 binds directly to tankyrases via motifs in its C-terminal region. Four of these RNF146 motifs represent novel, extended TBMs, that have one or two additional amino acids between the most conserved Arg and Gly residues. The individual RNF146 motifs display weak binding, but together mediate a strong multivalent interaction with the substrate-binding region of TNKS, forming a robust one-to-one complex. A crystal structure of the first RNF146 noncanonical TBM in complex with the second ankyrin repeat domain of TNKS shows how an extended motif can be accommodated in a peptide-binding groove on tankyrases. Overall, our work demonstrates the existence of a new class of extended TBMs that exist in previously uncharacterized tankyrase-binding proteins including those of IF4A1 and NELFE. This article is protected by copyright. All rights reserved.

Structural basis for tankyrase-RNF146 interaction reveals noncanonical tankyrase-binding motifs.,DaRosa PA, Klevit RE, Xu W Protein Sci. 2018 Mar 31. doi: 10.1002/pro.3413. PMID:29604130<ref>PMID:29604130</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6cf6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Da Rosa PA]]
[[Category: Xu W]]