CDK6 - Cyclin-dependent kinase 6 - human protein (Function)
 
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CDK6 »  Cyclin-dependent kinase 6   [ EC 2.7.11.22 ]
 
Protein also known as:  Serine/threonine-protein kinase PLSTIRE.
Gene name:  CDK6
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 148 1
GENE REF ISO

Function

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Overview 
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. Erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.  
9
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDABHF-UCL
Cyclin bindingdefinition[GO:0030332]  
1
  • IPIBHF-UCL
Cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0004693]  
1
  • IDABHF-UCL
Protein bindingdefinition[GO:0005515]  
16
  • IPIIntAct
  • IPIBHF-UCL
GO biological process 
Astrocyte developmentdefinition[GO:0014002]  
1
  • ISSUniProtKB
Cell cycle arrestdefinition[GO:0007050]  
1
  • TASUniProtKB
Cell dedifferentiationdefinition[GO:0043697]  
1
  • IMPBHF-UCL
Cell divisiondefinition[GO:0051301]  
  • IEAUniProtKB KW
Dentate gyrus developmentdefinition[GO:0021542]  
1
  • ISSUniProtKB
G1/S transition of mitotic cell cycledefinition[GO:0000082]  
1
  • TASUniProtKB
Generation of neuronsdefinition[GO:0048699]  
1
  • ISSUniProtKB
Gliogenesisdefinition[GO:0042063]  
1
  • IMPBHF-UCL
Lateral ventricle developmentdefinition[GO:0021670]  
1
  • ISSUniProtKB
Negative regulation of cell cycledefinition[GO:0045786]  
1
  • IDAUniProtKB
Negative regulation of cell differentiationdefinition[GO:0045596]  
1
  • TASUniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • TASUniProtKB
Negative regulation of cellular senescencedefinition[GO:2000773]  
1
  • IDAUniProtKB
Negative regulation of epithelial cell proliferationdefinition[GO:0050680]  
1
  • IMPBHF-UCL
Negative regulation of myeloid cell differentiationdefinition[GO:0045638]  
1
  • IDAUniProtKB
Negative regulation of osteoblast differentiationdefinition[GO:0045668]  
1
  • IDABHF-UCL
Positive regulation of cell-matrix adhesiondefinition[GO:0001954]  
1
  • IDABHF-UCL
Positive regulation of fibroblast proliferationdefinition[GO:0048146]  
1
  • IMPBHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDABHF-UCL
Regulation of cell motilitydefinition[GO:2000145]  
1
  • ISSUniProtKB
Regulation of erythrocyte differentiationdefinition[GO:0045646]  
1
  • IMPBHF-UCL
Regulation of gene expressiondefinition[GO:0010468]  
2
  • IMPBHF-UCL
Response to virusdefinition[GO:0009615]  
1
  • IEPUniProtKB
Type B pancreatic cell developmentdefinition[GO:0003323]  
1
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.22: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. Erythroid and osteoblast).  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+1021  
Chronic myeloid leukemia  hsa05220+1021  
Glioma  hsa05214+1021  
Measles  hsa05162+1021  
Melanoma  hsa05218+1021  
Non-small cell lung cancer  hsa05223+1021  
p53 signaling pathway  hsa04115+1021  
Pancreatic cancer  hsa05212+1021  
Pathways in cancer  hsa05200+1021  
Small cell lung cancer  hsa05222+1021  
According to Reactome, this protein belongs to the following pathways:
Cyclin D associated events in G1  REACT_821  
Oncogene Induced Senescence  REACT_169325  
Oxidative Stress Induced Senescence  REACT_169436  
Senescence-Associated Secretory Phenotype (SASP)  REACT_169168  
Note 
Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations.  
  • CuratedUniProtKB
Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
Differentiation  definition   [KW-0221]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Cyclin-dependent_kinase_6
GenomeRNAi: 1021
PRO: PR:Q00534
Chemistry
GuidetoPHARMACOLOGY: 1978