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==Structure of human CDC2-like kinase 2 (CLK2)==
==Structure of human CDC2-like kinase 2 (CLK2)==
<StructureSection load='3nr9' size='340' side='right' caption='[[3nr9]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
<StructureSection load='3nr9' size='340' side='right'caption='[[3nr9]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3nr9]] is a 3 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=3NR9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NR9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3nr9]] is a 3 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=3NR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NR9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NR9:(5Z)-5-(QUINOLIN-6-YLMETHYLIDENE)-2-[(THIOPHEN-2-YLMETHYL)AMINO]-1,3-THIAZOL-4(5H)-ONE'>NR9</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]] 2.89&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLK2 ([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=NR9:(5Z)-5-(QUINOLIN-6-YLMETHYLIDENE)-2-[(THIOPHEN-2-YLMETHYL)AMINO]-1,3-THIAZOL-4(5H)-ONE'>NR9</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=3nr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nr9 OCA], [https://pdbe.org/3nr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nr9 RCSB], [https://www.ebi.ac.uk/pdbsum/3nr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nr9 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=3nr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nr9 OCA], [http://pdbe.org/3nr9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nr9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nr9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nr9 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CLK2_HUMAN CLK2_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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref> <ref>PMID:8910305</ref> <ref>PMID:9637771</ref>
[https://www.uniprot.org/uniprot/CLK2_HUMAN CLK2_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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref> <ref>PMID:8910305</ref> <ref>PMID:9637771</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nr/3nr9_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nr/3nr9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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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: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Berridge, G]]
[[Category: Berridge G]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Chaikuad, A]]
[[Category: Chaikuad A]]
[[Category: Delft, F von]]
[[Category: Edwards AM]]
[[Category: Edwards, A M]]
[[Category: Eswaran J]]
[[Category: Eswaran, J]]
[[Category: Fedorov O]]
[[Category: Fedorov, O]]
[[Category: Filippakopoulos P]]
[[Category: Filippakopoulos, P]]
[[Category: Keates T]]
[[Category: Keates, T]]
[[Category: Knapp S]]
[[Category: Knapp, S]]
[[Category: Krojer T]]
[[Category: Krojer, T]]
[[Category: Muniz JRC]]
[[Category: Muniz, J R.C]]
[[Category: Phillips C]]
[[Category: Phillips, C]]
[[Category: Pike ACW]]
[[Category: Pike, A C.W]]
[[Category: Rellos P]]
[[Category: Rellos, P]]
[[Category: Savitsky P]]
[[Category: Structural genomic]]
[[Category: Weigelt J]]
[[Category: Savitsky, P]]
[[Category: Zhang Y]]
[[Category: Weigelt, J]]
[[Category: Von Delft F]]
[[Category: Zhang, Y]]
[[Category: Dual specificity protein kinase]]
[[Category: Protein kinase]]
[[Category: Sgc]]
[[Category: Transferase]]

Latest revision as of 12:19, 6 September 2023

Structure of human CDC2-like kinase 2 (CLK2)Structure of human CDC2-like kinase 2 (CLK2)

Structural highlights

3nr9 is a 3 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 2.89Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLK2_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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.[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.

See Also

References

  1. ↑ Moeslein FM, Myers MP, Landreth GE. The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 1999 Sep 17;274(38):26697-704. PMID:10480872
  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
  3. ↑ Lee K, Du C, Horn M, Rabinow L. Activity and autophosphorylation of LAMMER protein kinases. J Biol Chem. 1996 Nov 1;271(44):27299-303. PMID:8910305
  4. ↑ 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

3nr9, resolution 2.89Å

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OCA
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