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FLASH GENE
Symbol CCNF contributors: mct - updated : 13-07-2017
HGNC name cyclin F
HGNC id 1591
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 40AA F-box motif
  • a putative protein -protein interaction motif
  • a RRM2 binding domain
  • a cyclin box domain, but in contrast to most cyclins, it does not bind or activate any cyclin-dependent kinases (CDKs)
    • HOMOLOGY
    Homologene
    FAMILY F-box, Fbxs class, cyclin family of CDK kinase regulatory proteins
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • localizes to both the centrosomes and the nucleus
    • basic FUNCTION
  • plays a role in cell cycle regulation
  • CCNF(Cyclin F)-mediated degradation of CCP110 is potentially required for the fidelity of mitosis and genome integrity
  • controls centrosome duplication and prevents chromosome instability by promoting the degradation of CCP110
  • is a hub that coordinates and synchronizes centrosome duplication with DNA replication to ensure proper cell division
  • controls genome stability through ubiquitin-mediated proteolysis
  • plays an important role in checkpoint control following ionizing radiation
  • CCNF ubiquitin ligase complex prevents DNA re-replication by targeting CDC6 for proteasomal degradation late in the cell cycle
    • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    text G2/mitotic specific checkpoint
    PATHWAY
    metabolism
    signaling
    a component forming SCF complex (Skp1-Cdc53/Cul1-Fbox)
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding and activating cyclin dependent protein kinase
  • biinding to cyclin B
  • CCP110 is essential for centrosome duplication and is an interactor and substrate of CCNF
  • RRM2 is a new interactor of the F-box protein CCNF
  • directly controls the ubiquitin-mediated degradation of RRM2
  • interacts with MYBL2 via the cyclin box domain and this interaction is important to suppress CCNA-mediated phosphorylation of MYBL2, a key step in MYBL2 activation
  • CDC6 and CCNF interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation
  • CCNF-dependent degradation of E2F7 is critical for DNA repair and G2-phase progression
    • cell & other
    REGULATION
    Other degraded during G2-M by metalloproteases dependent proteolysis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    after DNA damage, CCNF is downregulated in an ATR-dependent manner to allow accumulation of RRM2
    Susceptibility to amyotrophic lateral sclerosis and frontotemporal dementia
    Variant & Polymorphism other expression of mutant CCNF in neuronal cells caused abnormal ubiquitination and accumulation of ubiquitinated proteins leading to ALS and FTD
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    CycF(-/-) animals, with a myriad of developmental anomalies due in large part to failures in yolk sac and chorioallantoic placentation, die around embryonic day 10.5