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FLASH GENE
Symbol CDC25A contributors: mct - updated : 10-09-2014
HGNC name cell division cycle 25 homolog A (S. pombe)
HGNC id 1725
Location 3p21.31      Physical location : 48.198.667 - 48.229.801
Synonym name
  • dual specificity phosphatase CDC25A
  • cell division cycle 25 homolog A (S. cerevisiae)
  • M-phase inducer phosphatase 1
    • Synonym symbol(s) CDC25A2
    EC.number 3.1.3.48
    DNA
    TYPE functioning gene
    STRUCTURE 31.13 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 3717 59 524 - 2000 11139144
    14 splicing 3597 54 484 - 2000 11139144
  • lacking an alternate in-frame exon compared to variant 1
  • having the same N- and C-termini compared to isoform a
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Reproductivefemale systemuteruscervix moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscular   highly
    cell lineage
    cell lines
    fluid/secretion predominantly in lymph
    at STAGE
    cell cycle     cell cycle, interphase, checkpoint, G1S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a phosphodegron motif
  • a rhodanese domain
    • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies homolog to rattus Cdc25a (86.4 pc)
    homolog to murine Cdc25a (86 pc)
    Homologene
    FAMILY
  • MPI phosphatase family
  • CDC25 family of phosphatases
    • CATEGORY enzyme , protooncogene , receptor membrane phosphatase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    text centrosomal protein
    basic FUNCTION
  • dual specificity (tyr/thr) phosphatase, putative upregulated c-Myc target gene
  • acting as a regulator of the cell cycle required for progression from G1 to S phase
  • functioning as a dosage-dependent inducer of mitotic progression
  • coordinate cell cycle progression through activating dephosphorylation of Cyclin-dependent kinases
  • directly dephosphorylating CDC2 and stimulating its kinase activity
  • has non-redundant functions in late G2/early M-phase as a major regulator of Cyclin A/kinase complexes
  • mainly involved in chromatin condensation and acts after Cdc25B in G2–M phase
  • can activate both Cdk1/Cyclin A and Cdk2/Cyclin A complexes in G2–M
  • may have an essential function during early embryonic development
  • with CSC25B and CDC25C, are implicated at G1/S, during S-phase, at G2/M and during mitosis (are implicated at G1/S, during S-phase, at G2/M and during mitosis
  • having effects on breast cancer cell metastasis, independent of cell proliferation and apoptosis
  • dual specificity protein phosphatase, exhibiting anti-apoptotic activity
  • has an important physiological role in NFKB activity regulation and it may be an important survival mechanism of cancer cells
  • FOXM1 controls the cell cycle through its association with CDC25A
  • CDC25A normally plays a pivotal role in regulating the G1/S and G2/M transitions by dephosphorylating and activating cyclin/cyclin-dependent kinase (CDK) complexes
    • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • ubiquitinated
    • INTERACTION
    DNA
    RNA
    small molecule other,
    protein
  • interacting with CCNB1/cyclin B1
  • interacting with YWHAE/14- 3-3 epsilon when phosphorylated
  • interacting with CUL1 specifically when CUL1 is neddylated and active
  • interacting with BOLL (a decreased CDC25A expression caused by lack or decrease of BOLL may be associated with male infertility)
  • interacting with BTRC/BTRCP1 and FBXW11/BTRCP2
  • interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage
  • TRIB3 is a regulator for adjusting the expression level of CDC25A both in a normal and a genotoxic conditions
  • enhancing FOXO1 stability by dephosphorylating CDK2
  • stimulates NFKB activity by destabilizing NFKBIA protein through inducing its phosphorylation and ubiquitination
  • FOXM1 directly regulates CDC25A gene transcription via direct promoter binding and indirect activation of E2F-dependent pathways
  • RPS6KA3 promotes G2/M transition in mammalian cells through activating phosphorylation of CDC25A and CDC25B
  • STK38-mediated phosphorylation of CDC25A at Ser-76 and the subsequent degradation of CDC25A are required to promote DNA damage-induced G2/M checkpoint activation
    • cell & other
    REGULATION
    activated by cyclin B
    inhibited by ubiquinated and degraded by the proteasome pathway
    phosphorylated and inactivated by CHEK1
    Other specifically degraded in response to DNA damage
    deubiquitinated by USP17L2
    stimulated by B-type cyclins
    ubiquitinated by CUL1
    phosphorylated by NEK11, phosphorylation that is required for its polyubiquitination and thus degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    associated with spermatogenic failure and failed sperm retrieval in infertile men
    constitutional     --over  
    initiates centrosome separation by activation of centrosomal Cdk1/Cyclin B pools
    tumoral     --over  
    in breast cancer cells enhances metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    anti-Cdc25A strategy may reveal its therapeutic potential in prevention and treatment of breast cancer cell dissemination
    digestiveliver 
    pharmacological targeting of CDC25A has therapeutic potential in polycystic liver diseases
    ANIMAL & CELL MODELS
    CDC25A-deficient embryos exhibit growth retardation and die before E7.5 through an apoptotic pathway