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FLASH GENE
Symbol CDK1 contributors: mct/ - updated : 27-12-2011
HGNC name cyclin-dependent kinase 1
HGNC id 1722
Location 10q21.2      Physical location : 62.538.088 - 62.554.604
Synonym name
  • cell division cycle 2, G1 to S and G2 to M
  • p34 protein kinase
  • cell cycle controller CDC2
  • cell division control protein 2 homolog
  • cell division protein kinase 1
  • Synonym symbol(s) CDC2, p34, CDC28A, DKFZp686L20222, MGC111195, P34CDC2
    EC.number 2.7.1. 22, 2.7.11.23
    DNA
    TYPE functioning gene
    STRUCTURE 16.39 kb     8 Exon(s)
    MAPPING cloned Y linked Y status confirmed
    Map cen - D10S589 - D10S1794 - CDK1 - D10S1640 - D10S609 - qter
    Authors CEPH (92)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1923 34.1 297 - - 3553962
    full length
    6 splicing 1752 27.5 240 breast cancer tissues - 3553962
  • also called variant 2/isoform 2 or CDC2 delta T
  • lacking an internal coding region compared to variant 1
  • the resulting protein lacks the T loop of the kinase domain and, thereby, lacks the kinase activity
  • being unable to complex with cyclin B1 and also failing to bind to the CDK inhibitor p21
  • - - 1742 - 109 - - 3553962
    also called variant 5/isoform 4
    - - 1754 - 109 - - 3553962
    also called variant 4/isoform 4
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     salivary gland   highly
    Endocrineadrenal gland   highly
    Lymphoid/Immunelymph node   predominantly
    Reproductivefemale systemuterus  moderately
     female systembreastmammary gland highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    cell cycle     cell cycle, checkpoint, G1S, G2M
    Text umbilical cord and embryonic tissue
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • serine/threonine kinase p34/cdc2 with the PSTAIRE motif
  • an ATP binding site
  • HOMOLOGY
    interspecies ortholog to Cdk1, Rattus norvegicus
    ortholog to CDK1, Mus musculus
    ortholog to cdk&, Danio rerio
    ortholog to CDK1, Pan troglodytes
    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,mitotic spindle
    intracellular,nucleus,nucleoplasm
    text continually shuttling between the nucleus and cytoplasm
    basic FUNCTION
  • directly regulates microtubule dynamics at mitosis through phosphorylation of MAP4 (
  • cdc2-mediated phosphorylation is an important regulator of nestin organization and dynamics during mitosis (
  • acting as an histone 1-kinase (H1K)
  • involved in cell cycle regulation (G1 to S and G2 to M transition)
  • phosphorylating JUNB and lowering its level in mitotic and early G1 cells
  • putative upregulated c-Myc target gene
  • 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
  • is the only essential cell cycle CDK (in the absence of interphase Cdks, CDC2 can execute all the events that are required to drive cell division)
  • can activate CDC25C
  • phosphorylates ELAVL1 during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence
  • essential for DNA replication downstream formation of replication initiation complexes in hepatocytes but not in fibroblasts
  • involved in CDK1 and CDK2-mediated phosphorylation, a key mechanism governing EZH2 function
  • promote interphase nuclear pore complexes formation in human dividing cells
  • with AURKA and PLK1, participate in a feedback activation loop and activation of CDK1 initiates the feedback loop activity, leading to rapid and timely entry into mitosis
  • implicated in phosphorylation of CHEK1 which participates in cytoplasmic sequestration of CHEK1 activity
  • CDK1, CDK2, CDK5, can phosphorylate human DNMT1 at Ser154, suggesting an important role for CDKs in controlling DNA methylation patterns in mammalian cells
  • robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of CDK1
  • CDK1 and AURKB cooperatively modulate microtubule dynamics and AURKB-dependent phosphorylation of INCENP controls spindle function by excluding the CPC from spindle regions engaged in microtubule polymerization
  • permits resection by phosphorylation of RBBP8 but also prevents RAD51 binding to the resected ends during M-phase double-strand break repair
  • is a critical regulator of DSB repair in M phase
  • archetypical kinase and a central regulator that drives cells through G2 phase and mitosis
  • essential for cell proliferation and tumorigenesis, it is not required for DNA replication and liver regeneration
  • is redundant for S phase progression, but its loss results in endoreduplication
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component with cyclin A and B1 of the M phase promoting factor (MPF)
  • being a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II
  • CDK1/CCNB1 activity shields cells against extrinsic death stimuli and unravel the molecular details of the crosstalk between cell cycle and extrinsic apoptotic pathways
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • proliferating cell nuclear antigen, PCNA (
  • kinase associated phosphatase, KAP (
  • cyclin A1 (
  • protein-tyrosine kinase Lck (
  • cyclin B (
  • Fanconi anemia polypeptide, FAC (
  • indirectly interact with TGFbeta RII via cyclin B2 (
  • LATS, large tumor suppressor, homolog 1 (Drosophila), LATS1 (
  • Cyclin B1 (
  • promyelocytic leukemia zinc finger, PLZF (
  • Myt1 (
  • survivin (
  • p53 (
  • Hamartin and tuberin (
  • FEZ1/LZTS1 (
  • CCAAT displacement protein (CDP)/Cux transcription factor (
  • response gene to complement 32 protein, RGC32 (
  • Gadd45b and Gadd45g (
  • WARTS protein kinase (
  • Disabled-2, Dab2 (
  • separase (
  • CDK1 bind to RALBP1 during mitosis, such that endocytosis is inhibited (increased expression of CDK1 inhibits transport function of RALBP1 and promotes apoptosis)
  • different levels of CCNB1-CDK1 kinase activity trigger different mitotic events, thus revealing how the remarkable reorganization of the cell is coordinated at mitotic entry
  • KMT2E is a novel cellular target of CDK1, and the phosphorylation of KMT2E may have an indispensable role in the mitotic progression
  • combined action of CDK1, NEK6, NEK7, and likely other kinases contributes to hyperphosphorylation of NUP98 during mitosis (
  • CEP63 binds to and recruits CDK1 to centrosomes, and thereby regulates mitotic entry (
  • positive feedback in Cdk1 activation serves to overcome the activity of Cdk-opposing phosphatases and thus sustains forward progression in mitosis (
  • CDK1/CCNB1-dependent hyper-phosphorylation of BCL2L11 during prolonged mitotic arrest is an important cell death signal
  • as cells progress through S phase, CCNA2 initially forms complexes with CDK2, and, later, most CCNA2 molecules are bound to CDK1
  • CDK1 and POU5F1 interplay to inhibit ES cell differentiation into trophectoderm and thereby maintain stemness
  • CDKN3 dephosphorylates threonine-161 of CDK1 during mitotic exit
  • cell & other
    REGULATION
    activated by
  • phosphorylation of the threonine T161
  • inhibited by
  • through phosphorylation on Y15 by WEE1, phosphorylation of Y15 has a key role in radiation-induced G2 delay
  • phosphorylation of tyrosine Y15 and threonine T14 by CDK7
  • onset of the anaphase
  • Phosphorylated by
  • increasig of WEE1 and PKMYT1 and the reduction of CDK1 and CCNB1 are involved in 1,25[OH]2VD3-induced G2/M arrest of keratinocyte (
  • casein kinase II, CKII (
  • myelin transcription factor 1, MYT1 (
  • Other
  • maintained in an inactive state by phosphorylation of WEE1 and MYT1
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    cells lacking CDK1 cannot proliferate but instead enter a senescent state and survive in culture medium
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential of CDK1 inhibitors in cancer therapy
    ANIMAL & CELL MODELS