ID:CDK6_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase 6; EC=2.7.11.22; AltName: Full=Cell division protein kinase 6; AltName: Full=Serine/threonine-protein kinase PLSTIRE; FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: 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). SUBUNIT: Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7- binding promotes D-type cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V- cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels. INTERACTION: P24385:CCND1; NbExp=2; IntAct=EBI-295663, EBI-375001; P30281:CCND3; NbExp=2; IntAct=EBI-295663, EBI-375013; Q16543:CDC37; NbExp=2; IntAct=EBI-295663, EBI-295634; P42771:CDKN2A; NbExp=9; IntAct=EBI-295663, EBI-375053; Q08050-1:FOXM1; NbExp=2; IntAct=EBI-295663, EBI-866499; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, ruffle. Note=Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. TISSUE SPECIFICITY: Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells. INDUCTION: Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry. PTM: Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity. POLYMORPHISM: Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIM:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits. MISCELLANEOUS: Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations. MISCELLANEOUS: Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdk6/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q00534
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_g1Pathway - Cell Cycle: G1/S Check Point h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth h_cellcyclePathway - Cyclins and Cell Cycle Regulation
Reactome (by CSHL, EBI, and GO)
Protein Q00534 (Reactome details) participates in the following event(s):
R-HSA-8938853 CDK6 binds RUNX1 R-HSA-182594 Association of INK4 with CDK4/6 R-HSA-8941895 Formation of CDK4/6:CCND complexes R-HSA-8941915 Cip/Kip CDK inhibitors bind CDK4/6:CCND complexes R-HSA-8942607 Tyrosine kinases phosphorylate Cip/Kip inhibitors bound to CDK4/6:CCND complexes R-HSA-8942836 CDK4/6:CCND complexes are activated by T-loop phosphorylation of CDK4/6 R-HSA-69227 Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes R-HSA-1226094 Cyclin D:Cdk4/6 mediated phosphorylation of p130 (RBL2) and dissociation of phosphorylated p130 (RBL2) from DP1:E2F4/5 complex R-HSA-1226095 Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex R-HSA-8934593 Regulation of RUNX1 Expression and Activity R-HSA-69231 Cyclin D associated events in G1 R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) R-HSA-2559585 Oncogene Induced Senescence R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-69236 G1 Phase R-HSA-2559583 Cellular Senescence R-HSA-212436 Generic Transcription Pathway R-HSA-453279 Mitotic G1-G1/S phases R-HSA-2262752 Cellular responses to stress R-HSA-73857 RNA Polymerase II Transcription R-HSA-69278 Cell Cycle (Mitotic) R-HSA-8953897 Cellular responses to external stimuli R-HSA-74160 Gene expression (Transcription) R-HSA-1640170 Cell Cycle
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
