Cyclin-dependent kinase 6

UniProt Q00534 Organism Homo sapiens Gene CDK6, CDKN6 EC 2.7.11.22

Also known as: CDK6, CDKN6

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 negatively regulates 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.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: CDK, CDK6, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 22

1BI7 X-ray 3.40A
1BI8 X-ray 2.80A
1BLX X-ray 1.90A
1G3N X-ray 2.90A
1JOW X-ray 3.10A
1XO2 X-ray 2.90A
2EUF X-ray 3.00A
2F2C X-ray 2.80A
3NUP X-ray 2.60A
3NUX X-ray 2.70A
4AUA X-ray 2.31A
4EZ5 X-ray 2.70A
… and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 41

Disease associations

OMIM:612223 RAW:OMIM_612223
microcephaly 12, primary, autosomal recessive MONDO:0014484

Drugs targeting this protein · 12

PHA-793887 inhibitor
PALBOCICLIB inhibitor
ABEMACICLIB inhibitor
RIBOCICLIB inhibitor
RIBOCICLIB SUCCINATE inhibitor
TRILACICLIB inhibitor
ALVOCIDIB inhibitor
RONICICLIB inhibitor
AT-7519 inhibitor
TRILACICLIB DIHYDROCHLORIDE inhibitor
AZD-5438 inhibitor
UCN-01 inhibitor

Related proteins · sequence + function similarity

Cyclin-dependent kinase 6 0.99
Cyclin-dependent kinase 4 0.95
Cyclin-dependent kinase 4 0.92
Cyclin-dependent kinase 1 0.92
Cyclin-dependent kinase B1-2 0.92
Cell division protein kinase 2 homolog CRK1 0.91
Cyclin-dependent kinase B1-1 0.91
Cell division control protein 2 homolog 1 0.91
Cyclin-dependent kinase 4 0.91
Cyclin-dependent kinase 5 homolog 0.90
Cyclin-dependent kinase 5 0.90
Cyclin-dependent kinase B1-1 0.90

Co-cited proteins · studied together in the literature

Cyclin-dependent kinase 6 1 shared papers
Cyclin-dependent kinase 4 inhibitor D 2 shared papers
F-box only protein 7 1 shared papers
Retinoblastoma-associated protein 2 shared papers
Runt-related transcription factor 1 1 shared papers
Nucleophosmin 1 shared papers
Cyclin-dependent kinase 17 1 shared papers
Cyclin-dependent kinase 18 1 shared papers
Cyclin-dependent kinase inhibitor 2A 1 shared papers
Hsp90 co-chaperone Cdc37 1 shared papers
Cyclin-dependent kinase-like 1 1 shared papers
Cyclin-dependent kinase 3 1 shared papers

Literature · 34 cited papers

CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly. Hum. Mol. Genet. · 2013
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6. J. Med. Chem. · 2010
Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6. Diabetes · 2010
Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathog. · 2010
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer · 2009
A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A. J. Cell Biol. · 2009
Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. EMBO J. · 2007
… and 22 more in the literature graph

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