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FLASH GENE
Symbol CDK6 contributors: mct/npt - updated : 26-09-2019
HGNC name cyclin-dependent kinase 6
HGNC id 1777
Corresponding disease
MCPH12 microcephaly 12, primary
Location 7q21.2      Physical location : 92.234.236 - 92.465.941
Synonym name
  • cell division protein kinase 6
  • serine/threonine-protein kinase PLSTIRE
    • Synonym symbol(s) PLSTIRE, MGC59692
    EC.number 2.7.11.22
    DNA
    TYPE functioning gene
    STRUCTURE 231.71 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D7S524 - D7S492 - ABCB4 - CDK6 - COL1A2 - D7S657
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 11628 - 326 - 1995 7566098
    8 - 11733 - 326 - 1995 7566098
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
     thymus   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, interphase, G1, checkpoint, G1S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PSTAIRE-like motif (PLSTIRE)
    • HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae cdc28
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • CDC2/CDKX subfamily
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    text
  • a majority of CDK6 is localized to the cytoplasm with concentrations of in the edges of the cytoplasm and in the cytoplasmic extensions of cells
  • associates with the centrosome during mitosis
    • basic FUNCTION
  • cyclin dependent kinase, involved in cell cycle regulation (G1 to S transition)
  • link growth factor stimulation with the onset of cell cycle progression
  • may play an important role in the development and/or progression of a subset of human prostate cancers by stimulating the activity of the AR
  • promotes cell cycle progression and is overexpressed in human lymphoid malignancies
  • required for Notch-dependent survival, proliferation, and differentiation
  • critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis
  • functions as a regulator of G(1) phase of the cell cycle
  • intrinsic key molecular regulator of the switch between proliferation and neuronal differentiation in the adult brain
  • required for early thymocyte development and tumorigenesis
  • regulates EYA2 activity, a mechanism that could be important in development and in cancer
  • CDK6 is critical effector of KMT2A fusions in leukemogenesis that might be targeted to overcome the differentiation block associated with KMT2A-rearranged RUNX1
  • is an important regulator of stem cell activation and an essential component of a transcriptional complex that suppresses EGR1 in hematopoietic stem cells [HSCs] and leukemic stem cells [LSCs]
  • CDK6 levels regulate quiescence exit in human hematopoietic stem cells
    • CELLULAR PROCESS cell cycle, progression
    PHYSIOLOGICAL PROCESS
    text negative control
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with cyclin D (D1, D2, D3)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylating RB1
  • target for TARDBP control and provide a possible mechanism of regulation
  • CCND3 and its partner CDK6 were required for the proliferation of Burkitt lymphoma (BL)
  • CDK6 connects cell-cycle progression to angiogenesis confirms CDK6 central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence CDKN2A
  • binds to and promotes degradation of the EYA2 protein (interaction suggesting that CDK6 regulates EYA2 activity, a mechanism that could be important in development and in cancer)
  • CDK6 physically and functionally interacts with the NFKB1 subunit RELA in the nucleus and is found at promoters of many transcriptionally active NFKB1 target genes
  • FBXO7 interacts with proteins that are not substrates of the ubiquitin proteasome system, such as CDK6 and PSMF1
  • SUMO1-CDK6 conjugation constitutes a mechanism of cell cycle control and inhibition of this SUMOylation pathway may provide a strategy for treatment of glioblastoma
  • ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6
  • NANOG may play important roles in spinal cord pathophysiology via interact with CDK6
  • RPS14 can act as a CDK4/6 inhibitor linking ribosome biogenesis defects to the main engine of cell cycle progression
  • CDK4/CDK6 regulate lysosome biogenesis through TFEB/TFE3
    • cell & other
    REGULATION
    Other CDK6 levels are specifically regulated by TARDBP
    CDK6 SUMOylation stabilizes the protein and drives the cell cycle for the cancer development and progression
    ASSOCIATED DISORDERS
    corresponding disease(s) MCPH12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms
    tumoral   translocation    
    dysregulated by translocation (2;7)(p12;q21-22 ) in spleen marginal zone lymphoma and non-Hodgkin lymphoma
    tumoral   translocation    
    in B-cell lymphoproliferative disorders (
    tumoral     --over  
    dramatically and selectively elevated in PARK2-expressing breast cancer cells (
    tumoral     --over  
    in lymphoid malignancies
    Susceptibility to rheumatoid arthritis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    specific therapeutic target in human lymphoid malignancies
    cancerhemopathy 
    potential therapeutic target in human lymphoid malignancies
    cancerhemopathy 
    treatment of Burkitt lymphoma cell lines with a CDK4/6 inhibitor not only caused cell cycle arrest but, unexpectedly, induced apoptosis
    ANIMAL & CELL MODELS