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| | ==Crystal structure of the tetratricopeptide repeat (TPR) motif of human dual specificity protein kinase Mps1== | | ==Crystal structure of the tetratricopeptide repeat (TPR) motif of human dual specificity protein kinase Mps1== |
| - | <StructureSection load='4h7x' size='340' side='right' caption='[[4h7x]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4h7x' size='340' side='right'caption='[[4h7x]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4h7x]] 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=4H7X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H7X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4h7x]] 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=4H7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H7X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4h7y|4h7y]]</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=4h7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h7x OCA], [https://pdbe.org/4h7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h7x RCSB], [https://www.ebi.ac.uk/pdbsum/4h7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h7x ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MPS1, MPS1L1, NCBI Reference Sequence NM_003318.4, TTK ([http://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'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </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=4h7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h7x OCA], [http://pdbe.org/4h7x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h7x RCSB], [http://www.ebi.ac.uk/pdbsum/4h7x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h7x ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN]] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref> | + | [https://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Dual specificity protein kinase|Dual specificity protein kinase]] | + | *[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dual-specificity kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Blundell TL]] |
| - | [[Category: Bolanos-Garcia, V M]] | + | [[Category: Bolanos-Garcia VM]] |
| - | [[Category: Chirgadze, D Y]] | + | [[Category: Chirgadze DY]] |
| - | [[Category: Cancer]]
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| - | [[Category: Chromosome instability]]
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| - | [[Category: Mitotic checkpoint]]
| + | |
| - | [[Category: Mitotic checkpoint kinase]]
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| - | [[Category: Transferase]]
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| Structural highlights
Function
TTK_HUMAN Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.[1]
Publication Abstract from PubMed
The SAC (spindle assembly checkpoint) is a surveillance system that ensures the timely and accurate transmission of the genetic material to offspring. The process implies kinetochore targeting of the mitotic kinases Bub1 (budding uninhibited by benzamidine 1), BubR1 (Bub1 related) and Mps1 (monopolar spindle 1), which is mediated by the N-terminus of each kinase. In the present study we report the 1.8 A (1 A=0.1 nm) crystal structure of the TPR (tetratricopeptide repeat) domain in the N-terminal region of human Mps1. The structure reveals an overall high similarity to the TPR motif of the mitotic checkpoint kinases Bub1 and BubR1, and a number of unique features that include the absence of the binding site for the kinetochore structural component KNL1 (kinetochore-null 1; blinkin), and determinants of dimerization. Moreover, we show that a stretch of amino acids at the very N-terminus of Mps1 is required for dimer formation, and that interfering with dimerization results in mislocalization and misregulation of kinase activity. The results of the present study provide an important insight into the molecular details of the mitotic functions of Mps1 including features that dictate substrate selectivity and kinetochore docking.
Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint).,Thebault P, Chirgadze DY, Dou Z, Blundell TL, Elowe S, Bolanos-Garcia VM Biochem J. 2012 Dec 15;448(3):321-8. doi: 10.1042/BJ20121448. PMID:23067341[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046
- ↑ Thebault P, Chirgadze DY, Dou Z, Blundell TL, Elowe S, Bolanos-Garcia VM. Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint). Biochem J. 2012 Dec 15;448(3):321-8. doi: 10.1042/BJ20121448. PMID:23067341 doi:http://dx.doi.org/10.1042/BJ20121448
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