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FLASH GENE
Symbol CCNA2 contributors: mct/npt - updated : 26-11-2015
HGNC name cyclin A2
HGNC id 1578
Location 4q27      Physical location : 122.737.599 - 122.745.088
Synonym name cyclin A
Synonym symbol(s) CCN1, CYCA, CCNA
DNA
TYPE functioning gene
STRUCTURE 7.49 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • TAAC element is present in the cellular senescence-inhibited gene, PCNA, and CCNA2 promoters
  • MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2811 48.5 432 - 2012 22745723
    8 splicing - - - . lower in proliferating fetal tissues and stronger in some differentiated adult tissues, especially, heart . exclusively in the cytoplasm 2012 22745723
  • partly retains Intron 6
  • induced a clear G1/S cell cycle arrest associated with a CDKN1B and CDKN1A upregulation and an inhibition of retinoblastoma protein phosphorylation
  • might play a role in regulating nondividing cell states such as terminal differentiation or senescence
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Reproductivefemale systemuteruscervix highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, interphase, S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY cyclin family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    text ER expression of CCND2 in association with HBV surface antigen leads to a centrosome duplication and transformation
    basic FUNCTION
  • putative upregulated c-Myc target gene
  • regulating late S and G2 phase of the cell cycle
  • regulates nuclear-envelope breakdown and the nuclear accumulation of cyclin B1
  • particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation
  • major regulator in vertebrate cell cycle, associated with cyclin-dependent kinase (CDK), and involved in S-phase progression and entry into mitosis
  • CCNA2 helps initiate mitosis, in part through its effects on CCNB1, and CCNB1 and CCNB2 are particularly critical for the maintenance of the mitotic state
  • role in activating CCNB/CDK1 through promoting NFYA dependent transcription of CCNB and CDC2
  • negatively controls cell motility by promoting RHOA activation, thus demonstrating a novel CCNA2 function in cytoskeletal rearrangements and cell migration
  • key regulator of S phase progression and entry into mitosis
  • RSLISD1, PCNA, and CCNA2, which promote cell cycle progression, are repressed permanently in senescent cells
  • creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation
  • functions as a timer in prometaphase to ensure efficient error correction, consistent with previous data showing a linear relationship between the duration of prometaphase and the level of CCNA2
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    text G2M checkpoint
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding and activating CDC2, CDK2
  • CCNA2/CDK2 specifically associates with APC in late G2 phase and phosphorylates it at Ser-1360, located in the mutation cluster region of APC
  • CCNA2 and MCM7 interact in the chromatin fraction (interaction with MCM7 is essential for the function of cyclin A in promoting S-phase entry)
  • CDK2/CCNA2 can phosphorylate and activate the transcription factor NFYA
  • potentiates the exchange activity of a RHOA-specific guanine nucleotide exchange factor
  • as cells progress through S phase, CCNA2 initially forms complexes with CDK2, and, later, most CCNA2 molecules are bound to CDK1
  • SP1 is a major regulator of periodic expression of CKAP2, and cell-cycle-dependent phosphorylation of SP1 mediated by CCNA2 can regulate the DNA-binding affinity of SP1
  • is potentially a novel regulator of mitotic CCCNA2 degradation independent of spindle assembly checkpoint (SAC)
  • CIZ1 is a nuclear matrix protein that cooperates with cyclin A2 (encoded by CCNA2) and CDK2 to promote mammalian DNA replication
  • 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
  • cell & other
    REGULATION
    Other eMgc target gene
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    implicated in the development and progression of a variety of cancers
    tumoral     --over  
    patients breast cancer with higher CCNA2 and ERBB2 expressions had significantly shorter disease-free survival periods
    constitutional     --over  
    overexpression not only causes premature S-phase entry but also induces prolongation of S phase
    tumoral     --other  
    aberrant expression of CCNA2 is commonly associated with Reed-Sternberg cell morphologic features in Hodgkin lymphoma probably through LMP1 signaling or other similar mechanisms in EBV- cases
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS