CDK6

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly.

Cyclin Dependent Kinase 6

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).

Astrocyte development Source: UniProtKB
Cell cycle arrest Source: UniProtKB
Cell dedifferentiation Source: BHF-UCL
Cell division Source: UniProtKB-KW
Dentate gyrus development Source: UniProtKB
G1/S transition of mitotic cell cycle Source: UniProtKB
Generation of neurons Source: UniProtKB
Gliogenesis Source: BHF-UCL
Lateral ventricle development Source: UniProtKB
Negative regulation of cell cycle Source: UniProtKB
Negative regulation of cell differentiation Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of cellular senescence Source: UniProtKB
Negative regulation of epithelial cell proliferation Source: BHF-UCL
Negative regulation of G1/S transition of mitotic cell cycle Source: Reactome
Negative regulation of monocyte differentiation Source: UniProtKB
Negative regulation of myeloid cell differentiation Source: UniProtKB
Negative regulation of osteoblast differentiation Source: BHF-UCL
Positive regulation of cell-matrix adhesion Source: BHF-UCL
Positive regulation of fibroblast proliferation Source: BHF-UCL
Protein phosphorylation Source: BHF-UCL
Regulation of cell cycle Source: GO_Central
Regulation of cell motility Source: UniProtKB
Regulation of erythrocyte differentiation Source: BHF-UCL
Regulation of gene expression Source: BHF-UCL
Response to virus Source: UniProtKB
Type B pancreatic cell development Source: UniProtKB

Centrosome; Nucleus; Cytoplasm; Ruffle. Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Localized to the cytosol of neurons and showed prominent staining around either side of the nucleus (By similarity). Present in the cytosol and in the nucleus in interphase cells and at the centrosome during mitosis from prophase to telophase (PubMed:23918663).

Microcephaly 12, primary, autosomal recessive (MCPH12): A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.

Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.