Cyclin-dependent kinase

spinqualitylabelsall models CDK2 (cyan) complex with cyclin A2 (green), ATP analog roscovitine and monothioglycerol (PDB code 3ddq) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Cyclin-dependent kinase (CDK) or Cell division protein kinase are serine/threonine protein kinases which are important to the regulation of the cell cycle. CDKs are small proteins which contain just a kinase domain. In order to function, CDK binds the regulatory protein cyclin. CDKs phosphorylate their substrates at a consensus tetrapeptide. The CDK classes differ by the binding cyclin and their function in human. CDK1 binds cyclin and forms a complex which phosphorylates a variety of substrates which are involved in cell cycle progression •CDK2 is involved in the control of the cell cycle. It interacts with the regulatory protein cyclin A2. Phosphorylation at Thr14 or Tyr15 inactivates it; phosphorylation at Thr160 (T160P) – activates it. See also Intrinsically Disordered Protein. •CDK3 binds cyclin C and functions during the G1 phase. •For details on CDK4 see Cyclin Dependent Kinase-4 and Palbociclib. CDK5 binds p53 and functions during transcription. •CDK6 binds cyclin D and functions during the G1 phase. See also Palbociclib and Abemaciclib. CDK7 may serve as a direct link between transcription regulation and the cell cycle. •CDK8 binds cyclin C and functions during transcription. •CDK9 regulates gene transcription elongation by phosphorylating the C-terminal domain of RNA polymerase II. •CDK11 plays a role in regulating cell cycle, RNA transcription and processing, neuronal function and apoptosis. •CDK12 phosphorylates the C-terminal domain of the large subunit of RNA polymerase II. Acts as a regulator of transcription elongation. •CDK13 is required for RNA splicing. •CDK16 plays a role in vesicle-mediated transport processes and exocytosis. See also Proteins involved in cancer. Relevance CDK is a potential target for anti-cancer therapy. Overexprssion of CDK2 is indicator of oral cancer. CDK2 may be a suitable drug target for melanoma. Inhibition of CDK5 alleviates the cardiac phenotypes of Timothy Syndrome. Up-regulated CDK6 activity is associated with several types of cancers and thus its inhibitors can serve as cancer drug targets. Overexprssion of CDK7 is associated with unfavorable prognosis of oral squamous cells carcinoma. CDK16 negatively modulates p53 signaling pathway to promote radio resistance and hence represents a therapeutic target for lung cancer radiotherapy. Disease CDK12 mutations have been found in several malignancies including ovarian carcinoma. Structural highlights The kinase ATP-binding active site is located in a cleft between the small N-lobe and the large C-lobe. Phosphorylated Thr near the binding site is required for kinase activity. 3D structures of cyclin-dependent kinase Cyclin-dependent kinase 3D structures

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