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FLASH GENE
Symbol CCNE1 contributors: mct/npt - updated : 09-11-2018
HGNC name cyclin E1
HGNC id 1589
Location 19q12      Physical location : 30.302.900 - 30.315.218
Synonym name
  • cyclin Es
  • cyclin Et
    • Synonym symbol(s) CCNE
    DNA
    TYPE functioning gene
    STRUCTURE 12.32 kb     12 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
    12 - 2021 - 410 - 2014 24947816
    G1/S-specific cyclin-E1
    - - - - 365 - 2014 24947816
  • also called CCNE1T
  • 45aa deleted 3' of cyclin box, repressed in terminally differentiated myeloic cells
  • low molecular weight (LMW) isoform in breast cancer cells and tumor
  • hyperactivate CDK2 and accelerate the G1-S phase of cell division tissue
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    respiratorylungbronchi   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Respiratoryepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    cell cycle     cell cycle, checkpoint, G1S
    Text highly in placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a modular centrosomal-targeting domain essential for promoting S phase entry in a CDK2-independent manner
    • HOMOLOGY
    Homologene
    FAMILY
  • cyclin family
  • cyclin E subfamily
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    text
  • localization of cyclin E on centrosomes is mediated by a 20-amino acid domain termed the centrosomal localization sequence (CLS)(Ferguson 2008)
  • expressed at the G 1/S phase transition of the cell cycle to drive the initiation of DNA replication and degraded during S/G2M
    • basic FUNCTION
  • regulating G1 to S transition of the cell cycle and promoting DNA synthesis
  • phosphorylating NPME, in association with CDK2, leading to the initiation of centrosome duplication
  • plays an essential role in the G(1)/S cell cycle transition and DNA replication (Mazumder 2007)
  • in addition to their function as CDK activators-CCNE1 play kinase-independent functions in cell-cycle progression (Geng 2007)
  • implicated in regulating centrosome duplication (Ferguson 2008)
  • cyclin E-dependent localization of MCM5 regulates centrosome duplication (Ferguson 2008)
  • ectopic expression of CCNE1 enhances the ubiquitin-dependent proteolysis of CCNE2, suggesting a potential cross-talk in the regulation of E-type cyclin activity
  • important regulator of cell-cycle progression (Potemski 2009)
  • role of E2F1-CCNE1-CCNE2 circuit in coronary smooth muscle cell proliferation
  • key role for CCNE1, CCNE2 in promoting megakaryocyte entry into S phase and hence, increase in the number of cell cycling cells and in augmenting polyploidization
  • role for CCNE1, CCNE2 in the development and function of the mammalian central nervous system and its subcellular localization in neurons is important
  • in urothelial cells, cyclin E is recruited to the nuclear matrix as cells differentiate
  • by causing DNA damage, accumulation of CCNE1 might trigger the keratinocyte mitosis checkpoints and in turn, terminal differentiation
  • overexpression of CCNE1 in human basal keratinocytes induced a mitosis block, re-replication and differentiation
  • TEAD1 may mediate muscle development through its target genes, MRPL21, NDUFA6 and CCNE1
  • CCNE1 drives the initiation of DNA replication, and deregulation of its periodic expression leads to mitotic delay associated with genomic instability
  • CCNE2 induction of genomic instability by a mechanism distinct from CCNE1 indicates that these two proteins have unique functions in a cancer setting
  • regulates the cell cycle transition from G1 to S phase and is degraded before entry into G2 phase
  • CCNE1, CCNE2 control chromosome pairing, telomere stability and CDK2 localization in male meiosis
  • CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of Postmenopausal osteoporosis
    • CELLULAR PROCESS cell cycle
    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 (Xie 2009)
    a component
  • complexing with CDK2
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly interact with and colocalize on centrosomes with the DNA replication factor MCM5 in a centrosomal localization sequence-dependent but CDK2-independent manner
  • association with XRCC6 induces the dissociation of BAX from XRCC6, followed by BAX activation (Mazumder 2007)
  • DDX3X is critical for translation of CCNE1 mRNA, which provides an alternative mechanism for regulating CCNE1 expression during the cell cycle
  • direct link between CCNE1, CCNE2 and HIF1A activities in mammary epithelial cells and implicating HIF1A is a mediator of proliferation-independent phenotypes associated with high CCNE1, CCNE2 expression in some human breast cancers
  • BMI1 has a critical role in stabilizing CCNE1 by repressing the expression of FBXW7, a substrate-recognition subunit of the SCF E3 ubiquitin ligase that targets CCNE1 for degradation
  • YWHAE regulates cardiogenesis and growth of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via both CCNE1 and CDKN1B
  • RSF1 interacts and collaborates with CCNE1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour-promoting functions of the RSF1/CCNE1 complex
  • KDM5A upregulated expression of CCND1 and CCNE1 while suppressing the expression of cyclin-dependent kinase inhibitor p27 (CDKN1B), each contributing to KDM5A-mediated cell proliferation
  • RHOBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting CCNE for ubiquitylation
  • novel role for CCNE1 beyond G1/S and into S/G2 phase, most likely by inducing the expression of subsequent CCNA2 and CCNB1 through LIN9
  • CSF2 accelerated the G1/S phase transition in endothelial progenitor cells (EPCs) by upregulating the expression of CCND1 and CCNE1
  • CDKN1A/CCNE1 pathway is crucial in modulating the anticlastogenic function of BMI1
  • HOXA7 stimulates human hepatocellular carcinoma proliferation through CCNE1/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
  • USP27X promoted CCCNE1 stability by negatively regulating its ubiquitination
  • CCNK-dependent, novel phosphorylation site in CCNE1 that disrupts its interaction with CDK2
    • cell & other
    REGULATION
    induced by Hedgehog for regulating cell growth and proliferation
    inhibited by PRMT5
    Other targeted by AGO for ubiquitin-dependent proteolysis
    ubiquitinated in vitro by ago
    regulated by FBXW7
    regulated by CARM1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in many tumors leading to a deregulated level of protein and kinase activity relative to the cell cycle and inducing chromosome instability
    tumoral     --over  
    significant factor of poor prognosis, especially in the node-positive groupof breast cancer (Potemski 2009)
    tumoral     --over  
    is associated with Stage 4 neuroblastomas and poor prognosis in patients
    tumoral   amplification --over  
    is amplified and overexpressed in osteosarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • highest positive predictive value for classical Hodgkin lymphoma (cHL)
    • Therapy target
    ANIMAL & CELL MODELS