3twr: Difference between revisions

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-[[Image:3twr.png|left|200px]]
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+==Crystal structure of ARC4 from human Tankyrase 2 in complex with peptide from human 3BP2==
-The line below this paragraph, containing "STRUCTURE_3twr", creates the "Structure Box" on the page.
+<StructureSection load='3twr' size='340' side='right'caption='[[3twr]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3twr]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TWR FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
--->
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SET:AMINOSERINE'>SET</scene></td></tr>
-{{STRUCTURE_3twr|  PDB=3twr  |  SCENE=  }}
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3twq|3twq]], [[3tws|3tws]], [[3twt|3twt]], [[3twu|3twu]], [[3twv|3twv]], [[3tww|3tww]], [[3twx|3twx]]</div></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP5B, TANK2, TNKL, TNKS2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=3twr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3twr OCA], [https://pdbe.org/3twr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3twr RCSB], [https://www.ebi.ac.uk/pdbsum/3twr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3twr ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[https://www.uniprot.org/uniprot/3BP2_HUMAN 3BP2_HUMAN]] Defects in SH3BP2 are the cause of cherubism (CRBM) [MIM:[https://omim.org/entry/118400 118400]]. CRBM is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.<ref>PMID:11381256</ref> <ref>PMID:12900899</ref> <ref>PMID:14577811</ref>
+== Function ==
+[[https://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] 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 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 poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>  [[https://www.uniprot.org/uniprot/3BP2_HUMAN 3BP2_HUMAN]] Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The poly(ADP-ribose)polymerases Tankyrase 1/2 (TNKS/TNKS2) catalyze the covalent linkage of ADP-ribose polymer chains onto target proteins, regulating their ubiquitylation, stability, and function. Dysregulation of substrate recognition by Tankyrases underlies the human disease cherubism. Tankyrases recruit specific motifs (often called RxxPDG "hexapeptides") in their substrates via an N-terminal region of ankyrin repeats. These ankyrin repeats form five domains termed ankyrin repeat clusters (ARCs), each predicted to bind substrate. Here we report crystal structures of a representative ARC of TNKS2 bound to targeting peptides from six substrates. Using a solution-based peptide library screen, we derive a rule-based consensus for Tankyrase substrates common to four functionally conserved ARCs. This 8-residue consensus allows us to rationalize all known Tankyrase substrates and explains the basis for cherubism-causing mutations in the Tankyrase substrate 3BP2. Structural and sequence information allows us to also predict and validate other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and MERIT40.
-===Crystal structure of ARC4 from human Tankyrase 2 in complex with peptide from human 3BP2===
+Structural basis and sequence rules for substrate recognition by tankyrase explain the basis for cherubism disease.,Guettler S, Larose J, Petsalaki E, Gish G, Scotter A, Pawson T, Rottapel R, Sicheri F Cell. 2011 Dec 9;147(6):1340-54. PMID:22153077<ref>PMID:22153077</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3twr" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22153077}}, adds the Publication Abstract to the page
+*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22153077 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22153077}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Human]]
-[[3twr]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TWR OCA].
+[[Category: Large Structures]]
+[[Category: Guettler, S]]
-==Reference==
+[[Category: Sicheri, F]]
-<ref group="xtra">PMID:022153077</ref><references group="xtra"/>
-[[Category: Homo sapiens]]
-[[Category: Guettler, S.]]
-[[Category: Sicheri, F.]]
 [[Category: Ankyrin repeat]]
 [[Category: Protein-protein interaction]]
 [[Category: Signaling protein-peptide complex]]
 [[Category: Substrate recruitment]]