Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

CDK6 (Q00534) - Overview - Molecular Target Synopsis


CDK6, Cyclin-dependent kinase 6
Enzyme Classification
UniProt Q00534

Also Known as CDK6_HUMAN, CDK6, CDKN6

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. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). 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.

Inspect Structure
See all 3D Structures for CDK6

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
326ENSG00000105810ENST00000265734, ENST00000424848ENSP00000265734, ENSP00000397087Q00534-1


CDK6 is targeted by Approved Drugs PD0332991, Ribociclib, Ribociclib Succinate. (see details)
Ribociclib Succinate

Sub-cellular localization

UniProt: CDK6 is active in the following subcellular-locations: cell projection, centrosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleus, ruffle.
GO terms: CDK6 is active in the following subcellular-locations: centrosome, cyclin D2-CDK6 complex, cyclin-dependent protein kinase holoenzyme complex, cytoplasm, cytosol, nucleoplasm, nucleus, ruffle.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project CDK6 has gain in 16 cell-lines, loss in 2 cell-lines and no signal in 986 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: MOLT_4, CCRF_CEM, LOXIMVI

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-M1, Jurkat, Clone E6-1, SU-DHL-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, SK-N-SH, HMEC

(see details)

RNA Interference

CDK6 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SCC47, HCC1954. (see details)

3D Structures

For CDK6 there are:
16 structures (18 chains) solved
11 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

CDK6 is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

CDK6 has been screened with 1060 compounds (1765 bioactivities), 281 compounds have bioactivities that show binding affinity of <= 500nM (289 bioactivities). (see details)