Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
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
    Physical map
    LOC121129 12q13.13 similar to seven transmembrane helix receptor LOC390329 12 similar to seven transmembrane helix receptor LOC121130 12q13.13 similar to seven transmembrane helix receptor PSMB3P 12q12 proteasome (prosome, macropain) subunit, beta type, 3 pseudogene MGC17301 12q13.13 hypothetical protein MGC17301 ITGA7 12q13.3 integrin, alpha 7 GCN5L1 12q13-q14 GCN5 general control of amino-acid synthesis 5-like 1 (yeast) RDH5 12q13-q14 retinol dehydrogenase 5 (11-cis and 9-cis) CD63 12q12-q13 CD63 antigen (melanoma 1 antigen) GDF11 12q12 growth differentiation factor 11 CIP29 12q13.13 cytokine induced protein 29 kDa ORMDL2 12q12 ORM1-like 2 (S. cerevisiae) DNAJ 12q13.13 DnaJ protein MMP19 12q14 matrix metalloproteinase 19 PYM 12q13.13 PYM protein DGKA 12q13.3 diacylglycerol kinase, alpha 80kDa SILV 12q13-q14 silver homolog (mouse) CDK2 12q13.3 cyclin-dependent kinase 2 SUOX RAB5B 12q13 RAB5B, member RAS oncogene family ZNFN1A4 12q13 zinc finger protein, subfamily 1A, 4 (Eos) RPS26 12q14 ribosomal protein S26 ERBB3 12q13.3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) PA2G4 12q13 proliferation-associated 2G4, 38kDa RPL41 12q14 ribosomal protein L41 FLJ14451 12q13.13 hypothetical protein FLJ14451 MBC2 12q13.13 hypothetical protein FLJ14451 MLC1SA 12q13.13 hypothetical protein FLJ14451 MYL6 12q12 myosin, light polypeptide 6, alkali, smooth muscle and non-muscle SMARCC2 12q13-q14 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 2 RNF41 12q13.13 ring finger protein 41 MGC2731 12q13.13 hypothetical protein MGC2731 SLC39A5 12q13.3 solute carrier family 39 (metal ion transporter), member 5 FLJ34236 12q13.13 hypothetical protein FLJ34236 FLJ32452 12q13.13 hypothetical protein FLJ32452
    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
  • 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
  • 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 (