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==Crystal Structure of CLK3==
==Crystal Structure of CLK3==
<StructureSection load='2eu9' size='340' side='right' caption='[[2eu9]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
<StructureSection load='2eu9' size='340' side='right'caption='[[2eu9]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2eu9]] is a 1 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=2EU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EU9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2eu9]] is a 1 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=2EU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EU9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.53&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2eu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eu9 OCA], [https://pdbe.org/2eu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2eu9 RCSB], [https://www.ebi.ac.uk/pdbsum/2eu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2eu9 ProSAT]</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=2eu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eu9 OCA], [http://pdbe.org/2eu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2eu9 RCSB], [http://www.ebi.ac.uk/pdbsum/2eu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2eu9 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CLK3_HUMAN CLK3_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:9637771</ref> <ref>PMID:19168442</ref>
[https://www.uniprot.org/uniprot/CLK3_HUMAN CLK3_HUMAN] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:9637771</ref> <ref>PMID:19168442</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2eu9 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2eu9 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Splicing requires reversible phosphorylation of serine/arginine-rich (SR) proteins, which direct splice site selection in eukaryotic mRNA. These phosphorylation events are dependent on SR protein (SRPK) and cdc2-like kinase (CLK) families. SRPK1 phosphorylation of splicing factors is restricted by a specific docking interaction whereas CLK activity is less constrained. To understand functional differences between splicing factor targeting kinases, we determined crystal structures of CLK1 and CLK3. Intriguingly, in CLKs the SRPK1 docking site is blocked by insertion of a previously unseen helix alphaH. In addition, substrate docking grooves present in related mitogen activating protein kinases (MAPKs) are inaccessible due to a CLK specific beta7/8-hairpin insert. Thus, the unconstrained substrate interaction together with the determined active-site mediated substrate specificity allows CLKs to complete the functionally important hyperphosphorylation of splicing factors like ASF/SF2. In addition, despite high sequence conservation, we identified inhibitors with surprising isoform specificity for CLK1 over CLK3.
Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.,Bullock AN, Das S, Debreczeni JE, Rellos P, Fedorov O, Niesen FH, Guo K, Papagrigoriou E, Amos AL, Cho S, Turk BE, Ghosh G, Knapp S Structure. 2009 Mar 11;17(3):352-62. PMID:19278650<ref>PMID:19278650</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2eu9" style="background-color:#fffaf0;"></div>


==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: Aerrowsmith, C]]
[[Category: Aerrowsmith C]]
[[Category: Bullock, A]]
[[Category: Bullock A]]
[[Category: Bunkoczi, G]]
[[Category: Bunkoczi G]]
[[Category: Das, S]]
[[Category: Das S]]
[[Category: Delft, F von]]
[[Category: Edwards A]]
[[Category: Edwards, A]]
[[Category: Fedorov O]]
[[Category: Fedorov, O]]
[[Category: Gileadi C]]
[[Category: Gileadi, C]]
[[Category: Knapp S]]
[[Category: Knapp, S]]
[[Category: Papagrigoriou E]]
[[Category: Papagrigoriou, E]]
[[Category: Rellos P]]
[[Category: Rellos, P]]
[[Category: Savitsky P]]
[[Category: Savitsky, P]]
[[Category: Sobott F]]
[[Category: Sobott, F]]
[[Category: Sundstrom M]]
[[Category: Sundstrom, M]]
[[Category: Turnbull A]]
[[Category: Turnbull, A]]
[[Category: Ugochukwu E]]
[[Category: Ugochukwu, E]]
[[Category: Weigelt J]]
[[Category: Weigelt, J]]
[[Category: Von Delft F]]
[[Category: Kinase domain]]
[[Category: Transferase]]

Latest revision as of 12:19, 14 February 2024

Crystal Structure of CLK3Crystal Structure of CLK3

Structural highlights

2eu9 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.
Method:X-ray diffraction, Resolution 1.53Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLK3_HUMAN Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.[1] [2]

Evolutionary Conservation

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

See Also

References

  1. ↑ Duncan PI, Stojdl DF, Marius RM, Scheit KH, Bell JC. The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. Exp Cell Res. 1998 Jun 15;241(2):300-8. PMID:9637771 doi:http://dx.doi.org/S0014-4827(98)94083-6
  2. ↑ Eisenreich A, Bogdanov VY, Zakrzewicz A, Pries A, Antoniak S, Poller W, Schultheiss HP, Rauch U. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res. 2009 Mar 13;104(5):589-99. doi: 10.1161/CIRCRESAHA.108.183905. Epub, 2009 Jan 22. PMID:19168442 doi:10.1161/CIRCRESAHA.108.183905

2eu9, resolution 1.53Å

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