3kr7: Difference between revisions

Revision as of 15:13, 24 December 2014

Human tankyrase 2 - catalytic PARP domain

Structural highlights

3kr7 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	GOL, SO4, ZN
Related:	3kr8
Gene:	PARP5B, TANK2, TNKL, TNKS2 (Homo sapiens)
Activity:	NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and suggests routes for further development of tankyrase inhibitors.

Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.,Karlberg T, Markova N, Johansson I, Hammarstrom M, Schutz P, Weigelt J, Schuler H J Med Chem. 2010 Jul 22;53(14):5352-5. PMID:20565110^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sbodio JI, Lodish HF, Chi NW. Tankyrase-2 oligomerizes with tankyrase-1 and binds to both TRF1 (telomere-repeat-binding factor 1) and IRAP (insulin-responsive aminopeptidase). Biochem J. 2002 Feb 1;361(Pt 3):451-9. PMID:11802774
↑ Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332-42. PMID:11739745
↑ Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16. PMID:19759537 doi:10.1038/nature08356
↑ Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang SM, Cong F. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011 May;13(5):623-9. doi: 10.1038/ncb2222. Epub 2011 Apr 10. PMID:21478859 doi:10.1038/ncb2222
↑ Karlberg T, Markova N, Johansson I, Hammarstrom M, Schutz P, Weigelt J, Schuler H. Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor. J Med Chem. 2010 Jul 22;53(14):5352-5. PMID:20565110 doi:10.1021/jm100249w

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Sbodio JI, Lodish HF, Chi NW. Tankyrase-2 oligomerizes with tankyrase-1 and binds to both TRF1 (telomere-repeat-binding factor 1) and IRAP (insulin-responsive aminopeptidase). Biochem J. 2002 Feb 1;361(Pt 3):451-9. PMID:11802774

[2] Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332-42. PMID:11739745

[3] Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16. PMID:19759537 doi:10.1038/nature08356

[4] Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang SM, Cong F. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011 May;13(5):623-9. doi: 10.1038/ncb2222. Epub 2011 Apr 10. PMID:21478859 doi:10.1038/ncb2222

[5] Karlberg T, Markova N, Johansson I, Hammarstrom M, Schutz P, Weigelt J, Schuler H. Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor. J Med Chem. 2010 Jul 22;53(14):5352-5. PMID:20565110 doi:10.1021/jm100249w

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3kr7]] is a 1 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=3KR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KR7 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kr8|3kr8]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kr8|3kr8]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP5B, TANK2, TNKL, TNKS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP5B, TANK2, TNKL, TNKS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kr7 RCSB], [http://www.ebi.ac.uk/pdbsum/3kr7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kr7 RCSB], [http://www.ebi.ac.uk/pdbsum/3kr7 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith, C H]]
-[[Category: Berg, S Van Den.]]
+[[Category: Berg, S Van Den]]
-[[Category: Berglund, H.]]
+[[Category: Berglund, H]]
-[[Category: Bountra, C.]]
+[[Category: Bountra, C]]
-[[Category: Collins, R.]]
+[[Category: Collins, R]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards, A M]]
-[[Category: Flodin, S.]]
+[[Category: Flodin, S]]
-[[Category: Flores, A.]]
+[[Category: Flores, A]]
-[[Category: Graslund, S.]]
+[[Category: Graslund, S]]
-[[Category: Hammarstrom, M.]]
+[[Category: Hammarstrom, M]]
-[[Category: Johansson, A.]]
+[[Category: Johansson, A]]
-[[Category: Johansson, I.]]
+[[Category: Johansson, I]]
-[[Category: Kallas, A.]]
+[[Category: Kallas, A]]
-[[Category: Karlberg, T.]]
+[[Category: Karlberg, T]]
-[[Category: Kotenyova, T.]]
+[[Category: Kotenyova, T]]
-[[Category: Kotzsch, A.]]
+[[Category: Kotzsch, A]]
-[[Category: Kraulis, P.]]
+[[Category: Kraulis, P]]
-[[Category: Moche, M.]]
+[[Category: Moche, M]]
-[[Category: Nielsen, T K.]]
+[[Category: Nielsen, T K]]
-[[Category: Nordlund, P.]]
+[[Category: Nordlund, P]]
-[[Category: Nyman, T.]]
+[[Category: Nyman, T]]
-[[Category: Persson, C.]]
+[[Category: Persson, C]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Structural genomic]]
-[[Category: Schuler, H.]]
+[[Category: Schuler, H]]
-[[Category: Schutz, P.]]
+[[Category: Schutz, P]]
-[[Category: Siponen, M I.]]
+[[Category: Siponen, M I]]
-[[Category: Thorsell, A G.]]
+[[Category: Thorsell, A G]]
-[[Category: Tresaugues, L.]]
+[[Category: Tresaugues, L]]
-[[Category: Weigelt, J.]]
+[[Category: Weigelt, J]]
-[[Category: Welin, M.]]
+[[Category: Welin, M]]
-[[Category: Wisniewska, M.]]
+[[Category: Wisniewska, M]]
 [[Category: Adp-ribosylation]]
 [[Category: Ank repeat]]
@@ Line 81: / Line 83: @@
 [[Category: Protein transport]]
 [[Category: Sgc]]
-[[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]
 [[Category: Telomere]]
 [[Category: Transferase]]

3kr7: Difference between revisions

Revision as of 15:13, 24 December 2014

Human tankyrase 2 - catalytic PARP domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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