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<StructureSection load='2x7f' size='340' side='right'caption='[[2x7f]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='2x7f' size='340' side='right'caption='[[2x7f]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2x7f]] is a 5 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=2X7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X7F FirstGlance]. <br>
<table><tr><td colspan='2'>[[2x7f]] is a 5 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=2X7F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X7F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=824:9-HYDROXY-4-PHENYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE'>824</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.8&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=824:9-HYDROXY-4-PHENYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE'>824</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=2x7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x7f OCA], [http://pdbe.org/2x7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x7f RCSB], [http://www.ebi.ac.uk/pdbsum/2x7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x7f ProSAT]</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=2x7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x7f OCA], [https://pdbe.org/2x7f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x7f RCSB], [https://www.ebi.ac.uk/pdbsum/2x7f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x7f ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TNIK_HUMAN TNIK_HUMAN]] Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322.<ref>PMID:10521462</ref> <ref>PMID:15342639</ref> <ref>PMID:19061864</ref> <ref>PMID:19816403</ref> <ref>PMID:20159449</ref> <ref>PMID:21690388</ref>
[https://www.uniprot.org/uniprot/TNIK_HUMAN TNIK_HUMAN] Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322.<ref>PMID:10521462</ref> <ref>PMID:15342639</ref> <ref>PMID:19061864</ref> <ref>PMID:19816403</ref> <ref>PMID:20159449</ref> <ref>PMID:21690388</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Alfano I]]
[[Category: Alfano, I]]
[[Category: Arrowsmith CH]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra C]]
[[Category: Bountra, C]]
[[Category: Bray J]]
[[Category: Bray, J]]
[[Category: Burgess-Brown N]]
[[Category: Burgess-Brown, N]]
[[Category: Chaikuad A]]
[[Category: Chaikuad, A]]
[[Category: Edwards A]]
[[Category: Delft, F von]]
[[Category: Fedorov O]]
[[Category: Edwards, A]]
[[Category: Filippakopoulos P]]
[[Category: Fedorov, O]]
[[Category: Gileadi O]]
[[Category: Filippakopoulos, P]]
[[Category: Knapp S]]
[[Category: Gileadi, O]]
[[Category: Mahajan P]]
[[Category: Knapp, S]]
[[Category: Muniz JRC]]
[[Category: Mahajan, P]]
[[Category: Phillips C]]
[[Category: Muniz, J R.C]]
[[Category: Pike ACW]]
[[Category: Phillips, C]]
[[Category: Roos A]]
[[Category: Pike, A C.W]]
[[Category: Shrestha B]]
[[Category: Roos, A]]
[[Category: Ugochukwu E]]
[[Category: Shrestha, B]]
[[Category: Vollmar M]]
[[Category: Ugochukwu, E]]
[[Category: Weigelt J]]
[[Category: Vollmar, M]]
[[Category: Von Delft F]]
[[Category: Weigelt, J]]
[[Category: Kinase]]
[[Category: Phosphoprotein]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]

Latest revision as of 13:25, 20 December 2023

Crystal structure of the kinase domain of human Traf2- and Nck- interacting Kinase with Wee1Chk1 inhibitorCrystal structure of the kinase domain of human Traf2- and Nck- interacting Kinase with Wee1Chk1 inhibitor

Structural highlights

2x7f is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TNIK_HUMAN Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322.[1] [2] [3] [4] [5] [6]

Evolutionary Conservation

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

References

  1. ↑ Fu CA, Shen M, Huang BC, Lasaga J, Payan DG, Luo Y. TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. J Biol Chem. 1999 Oct 22;274(43):30729-37. PMID:10521462
  2. ↑ Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, Uezato H, Nonaka S, Kariya K. The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004 Nov 19;279(47):49488-96. Epub 2004 Sep 1. PMID:15342639 doi:10.1074/jbc.M406370200
  3. ↑ Uechi Y, Bayarjargal M, Umikawa M, Oshiro M, Takei K, Yamashiro Y, Asato T, Endo S, Misaki R, Taguchi T, Kariya K. Rap2 function requires palmitoylation and recycling endosome localization. Biochem Biophys Res Commun. 2009 Jan 23;378(4):732-7. doi:, 10.1016/j.bbrc.2008.11.107. Epub 2008 Dec 4. PMID:19061864 doi:http://dx.doi.org/10.1016/j.bbrc.2008.11.107
  4. ↑ Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, Heck AJ, Clevers H. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009 Nov 4;28(21):3329-40. doi: 10.1038/emboj.2009.285. Epub 2009 Oct 8. PMID:19816403 doi:http://dx.doi.org/10.1038/emboj.2009.285
  5. ↑ Kawabe H, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee J, Brose N. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007. PMID:20159449 doi:10.1016/j.neuron.2010.01.007
  6. ↑ Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L. Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11127-32. doi:, 10.1073/pnas.1104128108. Epub 2011 Jun 20. PMID:21690388 doi:http://dx.doi.org/10.1073/pnas.1104128108

2x7f, resolution 2.80Å

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