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FLASH GENE
Symbol CCNF contributors: mct - updated : 13-07-2017
HGNC name cyclin F
HGNC id 1591
DNA
TYPE functioning gene
STRUCTURE 33.42 kb     17 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 4287 - 786 - 2015 25557911
16 - 4196 - 478 - 2015 25557911
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systembreastmammary gland highly
 female systemuteruscervix highly
Respiratoryrespiratory tractlarynx  highly
cell lineage
cell lines
fluid/secretion
at STAGE
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