CCNF
Developmental stage
Appears in S phase, peaks in G2 phase, decreases in mitosis, lowest in early G1 phase and then accumulates again in late G1 and S phase (at protein level).
Domain
The nuclear localization signals mediate the localization to the nucleus and are required for CCNB1 localization to the nucleus.
The D box motifs 1-5 (amino acid sequence RxxL) are involved in substrate binding, such as FZR1/CDH1, and may be ubiquitinated.
Function
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20596027, PubMed:22632967, PubMed:26818844, PubMed:27080313, PubMed:27653696, PubMed:28852778). The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle (PubMed:20596027, PubMed:26818844, PubMed:27653696, PubMed:8706131). Mediates the substrate recognition and the proteasomal degradation of various target proteins involved in the regulation of cell cycle progression and in the maintenance of genome stability (PubMed:20596027, PubMed:22632967, PubMed:26818844, PubMed:27653696). Mediates the ubiquitination and proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication (PubMed:20596027). In G2, mediates the ubiquitination and subsequent degradation of ribonucleotide reductase RRM2, thereby maintaining a balanced pool of dNTPs and genome integrity (PubMed:22632967). In G2, mediates the ubiquitination and proteasomal degradation of CDC6, thereby suppressing DNA re-replication and preventing genome instability (PubMed:26818844). Involved in the ubiquitination and degradation of the substrate adapter CDH1 of the anaphase-promoting complex (APC/C), thereby acting as an antagonist of APC/C in regulating G1 progression and S phase entry (PubMed:27653696). May play a role in the G2 cell cycle checkpoint control after DNA damage, possibly by promoting the ubiquitination of MYBL2/BMYB (PubMed:25557911).
Involvement in disease
Frontotemporal dementia and/or amyotrophic lateral sclerosis 5
FTDALS5
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS5 is an autosomal dominant form with age-dependent penetrance. Penetrance is estimated to be 50% by age 56 and 100% by age 61.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Degraded when the spindle assembly checkpoint is activated during the G2-M transition. Degradation depends on the C-terminal PEST sequence.
Phosphorylated just before cells enter into mitosis.
Ubiquitinated by the anaphase-promoting complex (APC/C); leading to its degradation by the proteasome.
Sequence Similarities
Belongs to the cyclin family. Cyclin AB subfamily.
Tissue Specificity
Widely expressed, with expression detected in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Cellular localization
- Nucleus
- Cytoplasm
- Perinuclear region
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Localization to the centrosome is rare in S phase cells and increases in G2 cells. Localizes to both the mother and daughter centrioles. Localization to centrosomes is not dependent on CP110. Localizes to the nucleus in G2 phase.
Alternative names
FBX1, FBXO1, CCNF, Cyclin-F, F-box only protein 1