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FLASH GENE

Symbol

CCNF

contributors: mct - updated : 13-07-2017

HGNC name	cyclin F
HGNC id	1591

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system breast mammary gland   highly   female system uterus cervix   highly Respiratory respiratory tract larynx     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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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