Names & Taxonomy

Uniprot ID:
Q00534
Entry Name:
CDK6_HUMAN
Status:
reviewed
Protein Names:
Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE)
Gene Names:
CDK6 CDKN6
Gene Names Primary:
CDK6
Organism:
Homo sapiens (Human)

Structure

Length:
326
Sequence:
MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIREVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGEEDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYFQDLERCKENLDSHLPPSQNTSELNTA
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm. Nucleus. Cell projection, ruffle. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Function

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. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
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).
Active Site:
ACT_SITE 145 145 Proton acceptor.
Cross Reference Drug Bank:
DB09073
Gene Ontology Go:
centrosome
cyclin-dependent protein kinase holoenzyme complex
cytoplasm
cytosol
nucleoplasm
nucleus
ruffle
ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
astrocyte development
cell cycle arrest
cell dedifferentiation
cell division
dentate gyrus development
G1/S transition of mitotic cell cycle
generation of neurons
gliogenesis
hematopoietic stem cell differentiation
lateral ventricle development
mitotic cell cycle
negative regulation of cell cycle
negative regulation of cell differentiation
negative regulation of cell proliferation
negative regulation of cellular senescence
negative regulation of epithelial cell proliferation
negative regulation of myeloid cell differentiation
negative regulation of osteoblast differentiation
Notch signaling pathway
positive regulation of cell-matrix adhesion
positive regulation of fibroblast proliferation
positive regulation of gene expression
protein phosphorylation
regulation of cell motility
regulation of erythrocyte differentiation
regulation of gene expression
response to virus
T cell differentiation in thymus
type B pancreatic cell development
Gene Ontology Biological Process:
astrocyte development
cell cycle arrest
cell dedifferentiation
cell division
dentate gyrus development
G1/S transition of mitotic cell cycle
generation of neurons
gliogenesis
hematopoietic stem cell differentiation
lateral ventricle development
mitotic cell cycle
negative regulation of cell cycle
negative regulation of cell differentiation
negative regulation of cell proliferation
negative regulation of cellular senescence
negative regulation of epithelial cell proliferation
negative regulation of myeloid cell differentiation
negative regulation of osteoblast differentiation
Notch signaling pathway
positive regulation of cell-matrix adhesion
positive regulation of fibroblast proliferation
positive regulation of gene expression
protein phosphorylation
regulation of cell motility
regulation of erythrocyte differentiation
regulation of gene expression
response to virus
T cell differentiation in thymus
type B pancreatic cell development
Gene Ontology Molecular Function:
ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
Gene Ontology Cellular Component:
centrosome
cyclin-dependent protein kinase holoenzyme complex
cytoplasm
cytosol
nucleoplasm
nucleus
ruffle
Keywords:
3D-structure
ATP-binding
Acetylation
Cell cycle
Cell division
Cell projection
Complete proteome
Cytoplasm
Cytoskeleton
Differentiation
Disease mutation
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Primary microcephaly
Reference proteome
Serine/threonine-protein kinase
Transferase
Interacts With:
P24385; P30281; Q16543; P42771; P42772; P42773; P55273; Q08050-1; P08238; Q01196

Publication

PubMed ID:
1639063 14702039 12853948 12690205 15489334 8114739 9482106 12833137 14985467 15254224 16096642 15809340 15592455 16548883 17431401 17420273 19139263 19369195 19690332 19608861 20668294 20333249 16294322 19238148 21269460 22814378 23918663 9751050 11124804 11828325 15689157 16789739 21038853 17344846