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FLASH GENE
Symbol CDK2 contributors: mct/npt/shn/pgu - updated : 24-12-2016
HGNC name cyclin-dependent kinase 2
HGNC id 1771
Location 12q13.2      Physical location : 56.360.555 - 56.366.567
Synonym name
  • p33 protein kinase
  • cdc2-related protein kinase
  • cell devision kinase 2
  • cell division protein kinase 2
  • Synonym symbol(s) p33, p33(CDK2)
    EC.number 2.7.11.22
    DNA
    TYPE functioning gene
    STRUCTURE 6.01 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure
  • two SP1 sites
  • MAPPING cloned Y linked N status confirmed
    Map ceb - D12S1724 - D12S1035 - CDK2 - D12S1632 - D12S1644 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 2325 33.8 298 - 2010 20195506
  • a seven exons variant
  • 6 splicing 2223 29.95 264 - 2010 20195506
  • a six exons variant
  • lacking exon five
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
     vessel   moderately
    Digestiveintestinesmall intestine  moderately
    Endocrineadrenal gland   moderately
    Lymphoid/Immunespleen   moderately
     thymus   highly
    Nervousnerve   moderately
    Reproductivefemale systemplacenta  moderately
     female systemuteruscervix highly
    Respiratoryrespiratory tracttrachea  moderately
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    cell cycle     cell cycle, G1, S, checkpoint, G1S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PSTAIRE motif
  • N terminal domain binding cyclins
  • a C terminal domain binding CSR1
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae cdc28
    ortholog to Cdk2, Mus musculus
    ortholog to Cdk2, Rattus norvegicus
    ortholog to cdk2, Pan troglodytes
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase
  • CDK subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • CCNA1/CDK2 localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase
  • basic FUNCTION
  • complexing and phosphorylating with cyclin E (CCNE1) for the regulation of chromosome stability
  • leading to the initiation of centrosome duplication
  • encoding a key regulator of the G1/S phase transition
  • having an activity upon SMAD3, its major physiologic substrate
  • phosphorylating the linker histone H1, thus providing a signal for the disassembly of higher order chromatin structure during interphase
  • phosphorylating FOXO1, resulting in cytoplasmic localization and inhibition of FOXO1 and regulating apoptotic cell death after DNA strand breakage
  • involved in apoptosis upon its regulation by p21
  • phosphorylating RIalpha and thus promoting the dissociation of the RIalpha-RFC40 complex (Replication Factor C) and subsequently the association of the RFC40-RFC37 complex
  • destabilizing p21 via the cy2 cyclin-binding motif and p21 phosphorylation
  • phosphorylating BARD1 and consequently down-regulating the ubiquitin-ligase activity of BRCA1-BARD1
  • essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase (
  • major regulator of S-phase entry
  • dispensable for neural progenitor cells proliferation, differentiation and survival of adult-born dentate gyrus granule neurons
  • G2 phase CCNA1/CDK2 controls the timing of entry into mitosis by controlling the subsequent activation of CCNB/CDK1, but also has an unexpected role in coordinating the activation of CCNB/CDK1 at the centrosome and in the nucleus
  • functionning as a progesterone receptor coactivator
  • playing an important role in cell cycle regulation in embryonic stem cells that are likely to bear significant impacts on the maintenance of their pluripotent phenotype
  • having a role in the G1 to S phase transition in embryonic stem cells
  • S-phase CDK, uniquely controls the G2/M checkpoint that prevents cells with damaged DNA from initiating mitosis
  • maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent TP53-independent G2/M checkpoint activation
  • involved in CDK1 and CDK2-mediated phosphorylation, a key mechanism governing EZH2 function
  • promote interphase nuclear pore complexes formation in human dividing cells
  • controls cell cycle progression of oligodendrocyte progenitor cell (
  • dispensable for myelination but is important for adult oligodendrocyte progenitor cell renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin (
  • CDK1, CDK2, CDK5, can phosphorylate human DNMT1 at Ser154, suggesting an important role for CDKs in controlling DNA methylation patterns in mammalian cells
  • cooperative function between CDK2 and SEPTIN2
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    CCNE1/CDK2/NPAT/HINFP pathway that is required for cell cycle-dependent activation of histone H4 genes at the G1/S phase transition
  • putative checkpoint between cell cycle and cell death pathway
  • a component
  • catalytic subunit of the cyclin dependent protein kinase complex
  • CDK2/CDK4/NPM pathway is a major guardian of centrosome dysfunction and genomic integrity
  • CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • cyclin E (
  • E2F transcription factor 1, E2F1 (
  • kinase-associated phosphatase, KAP (
  • cyclin-dependent kinase interactor 1, Cdi1 (
  • CksHs1 (
  • Cdc25 (
  • cyclin A (
  • Lyn tyrosine kinase (
  • p130 (
  • BRCA1a and BRCA1b (
  • H-1 kinase (
  • pol delta (
  • NF-kappa B (
  • cyclin E2 (
  • cell division cycle 6 homolog (S. cerevisiae), CDC6 (
  • p38 mitogen-activated protein kinase (
  • TOK-1alpha (
  • proliferating cell nuclear antigen, PCNA ( )
  • p12(DOC-1) (
  • protein kinase C eta, PKCeta (
  • HIR histone cell cycle regulation defective homolog A (S. cerevisiae), HIRA (
  • Cyclin A1 (
  • CDK-interacting protein phosphatase KAP (
  • transcription factor CCAAT/enhancer binding protein alpha, C/EBPalpha (
  • Speedy, Spy1 (
  • Cyclin B3, CCNB3 (
  • INCA1, KARCA1, PROCA1, GPS2, Ku70, receptor for activated protein kinase C1/guanine nucleotide-binding protein beta-2-like-1, and RBM4 (
  • NIRF (
  • Smad3 (
  • human O(6)-methylguanine-DNA methyltransferase, MGMT (
  • PURA
  • ANKRD17
  • CCNE2-CDK2 activation by estrogen occurs via E2F- and CHD8-mediated transcription of CCNE2 downstream of CCND1
  • KAT2B directly interacts with CDK2 (this interaction is mainly produced during S and G(2)/M phases of the cell cycle)
  • phosphorylating USP37, and stimulating its full activity
  • as cells progress through S phase, CCNA2 initially forms complexes with CDK2, and, later, most CCNA2 molecules are bound to CDK1
  • through activation of a centrosomal pool of CDK2, CDC25B stabilises the local pool of Monopolar spindle 1 (Mps1) which in turn regulates the level of CETN2 at the centrosome
  • CDK2 negatively regulates the stability and activity of FOXP3 and implicate CDK-coupled receptor signal transduction in the control of regulatory T cell function and stability
  • CDK2AP1 suppresses cell growth, differentiation and angiogenesis in numerous types of carcinoma by interacting with certain cell cycle proteins, including CDK2
  • interaction of MYBBP1A with CDK2 and TPP2, to form a protein-protein interaction network
  • HOXA7 stimulates human hepatocellular carcinoma proliferation through CCNE1/CDK2
  • CIZ1 is a nuclear matrix protein that cooperates with cyclin A2 (encoded by CCNA2) and CDK2 to promote mammalian DNA replication
  • CDK2 phosphorylation regulates the protein stability of KLF10 by interfering with binding of the E3 ligase SIAH1
  • CCP110 is a critical mediator of CDK2 inhibition-driven anaphase catastrophe
  • in addition to drive cell cycle progression, CDK2 also targets RNF4, which is involved in the regulatory network of DSBs repair
  • PLA2G4A acts as a bridge in the formation of a multiprotein complex at the G2-to-M transition to promote binding of SIRT2 to CCNA2-CDK2
  • CIAPIN1 played an important role in the proliferation of liver cancer cells through increasing the expressions of cell cycle related proteins CCND1, CDK2, CDK4, and CCNE1
  • CCNK-dependent, novel phosphorylation site in CCNE1 that disrupts its interaction with CDK2
  • cell & other
    REGULATION
    activated by association with cyclins and phosphorylation by CAK, leading to cell proliferation
    membrane depolarization
    p42 (
    Cyclin-dependent kinase 7, CDK7 (
    Speedy, Spy1 (
    inhibited by p21 (
    transcription factor CCAAT/enhancer binding protein alpha, C/EBPalpha (
    repressed by IRF1, by interfering with SP1 activation of the promoter
    Other regulated in apoptosis by TP53,BAX and BCL2
    translationnally down-regulated in replicative senescence of endothelial cells
    transcriptionally regulated by melanocyte lineage transcription factor MITF
    inactivated by Skp2 (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in suprabasal layers of perilesional (unaffected) skin, indicating that pemphigus vulgaris -induced changes in CDK2 levels may precede the phenotypic manifestations of disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • may be a suitable drug target in melanoma because of its depletion suppressing growth and cell cycle progression
  • interfering RNA depletion of Cdk2 prevented cell-cell detachment induced by pemphigus vulgaris sera (
  • pharmacological inhibition of Cdk2 activity through roscovitine prevented blister formation and acantholysis in the mouse model of the pemphigus vulgaris disease (
  • ANIMAL & CELL MODELS
  • mouse embryonic fibroblats lacking CDK2 proliferates normally and become immortal after continuous passage in culture (
  • Cdk2-/- mice are viable and survive for up to two years (
  • Cdk2 loss does not affect oligodendrocyte progenitor cell cell cycle, oligodendrocyte cell numbers, or myelination during central nervous system development (