Dual specificity protein kinase

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== Function ==
== Function ==
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'''Dual specificity protein kinases''' are kinases which act as both tyrosine kinase and serine/threonine kinase. '''CLK1''' phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing.
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'''Dual specificity protein kinases''' are kinases which act as both tyrosine kinase and serine/threonine kinase.
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*'''CLK1''' phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing.
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*'''Clk2''' and '''Clk3''' cause the redistribution of SR proteins and can regulate the alternative splicing of precursor mRNA<ref>PMID:9637771</ref>.
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*'''CLK4''' phosphorylates tyrosine or serine/threonine<ref>PMID:35092699</ref>.
== Structural highlights ==
== Structural highlights ==
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The dual specificity protein kinase '''TTK''' or '''monopolar spindle kinase 1''' contains tetratricopeptide repeat domain (TPR) which serves as interaction domain between proteins. The TPR domain is a helical 34 amino acid motif which is found in several copies in a protein which fold together forming a protein-protein binding domain. Cancer therapy potential drugs bind in <scene name='46/468134/Cv/2'>TTK active site</scene>.<ref>PMID:9779990</ref><ref>PMID:21159646</ref>
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The dual specificity protein kinase '''TTK''' or '''monopolar spindle kinase 1''' contains tetratricopeptide repeat domain (TPR) which serves as interaction domain between proteins. The TPR domain is a helical 34 amino acid motif which is found in several copies in a protein which fold together forming a protein-protein binding domain. Cancer therapy potential drugs bind in <scene name='46/468134/Cv/3'>TTK active site</scene>.<ref>PMID:9779990</ref><ref>PMID:21159646</ref>
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</StructureSection>
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==3D structures of dual specificity protein kinase==
==3D structures of dual specificity protein kinase==
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[[Dual specificity protein kinase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*CLK1 kinase domain
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**[[1z57]] – hCLK1 + himenialdizine – human
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**[[5j1v]], [[5j1w]], [[2vag]], [[5x8i]] – hCLK1 + inhibitor<br />
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**[[6g33]] – hCLK1 + iodotubercidine inhibitor<br />
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*CLK2 kinase domain
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**[[3nr9]] – hCLK2<br />
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**[[5unp]] – hCLK2 + inhibitor<br />
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*CLK3
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**[[2eu9]] – hCLK3
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**[[2exe]] – hCLK3 kinase domain, phosphorylated
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**[[2wu6]], [[2wu7]] – hCLK3 kinase domain + inhibitor
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**[[3raw]] - hCLK3 kinase domain + leucettine
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*TTK
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**[[3cek]], [[3dbq]], [[2zmc]] – hTTK kinase domain<br />
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**[[4b94]], [[4h7x]], [[4h7y]] - hTTK TPR domain<br />
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**[[3gfw]] - hTTK kinase domain + pyrolo-pyridin ligand
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**[[3h9f]] - hTTK kinase domain + pyrimidino-diazepin ligand
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**[[2x9e]], [[3vqu]], [[3w1f]], [[4bhz]], [[4bi0]], [[4bi1]], [[4bi2]], [[4c4e]], [[4c4f]], [[4c4g]], [[4c4h]], [[4c4i]], [[4c4j]], [[4js8]], [[4jt3]], [[3wzj]], [[3wzk]], [[4o6l]], [[5ehl]], [[5eho]], [[5ehy]], [[5ei2]], [[5ei6]], [[5ei8]], [[5ap0]], [[5ap1]], [[5ap2]], [[5eh0]], [[4zeg]], [[6b4w]], [[5na0]], [[5n9s]], [[5n93]], [[5n87]], [[5n84]], [[5n7v]] - hTTK kinase domain + inhibitor
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**[[2zmd]], [[5ap3]], [[5ap4]], [[5ap5]], [[5ap6]], [[5ap7]], [[5o91]], [[5ntt]], [[5nad]], [[5mrb]] - hTTK kinase domain (mutant) + inhibitor<br />
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**[[3hmn]] - hTTK kinase domain + ATP
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**[[3hmo]] - hTTK kinase domain + staurosporine
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**[[3hmp]] - hTTK kinase domain + quinazoline ligand<br />
 
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**[[5ljj]] - hTTK kinase domain + reversine<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Dual specificity protein kinase TTK kinase domain complex with inhibitor, 2x9e

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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. ↑ Shen Y, Zhang H, Yao S, Su F, Wang H, Yin J, Fang Y, Tan L, Zhang K, Fan X, Zhong M, Zhou Q, He J, Zhang Z. Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy. Clin Transl Med. 2022 Jan;12(1):e719. PMID:35092699 doi:10.1002/ctm2.719
  3. ↑ Dhanasekaran N, Premkumar Reddy E. Signaling by dual specificity kinases. Oncogene. 1998 Sep 17;17(11 Reviews):1447-55. PMID:9779990 doi:http://dx.doi.org/10.1038/sj.onc.1202251
  4. ↑ Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J. Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646 doi:10.1158/0008-5472.CAN-10-2101

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