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FLASH GENE

Symbol

CCNE1

contributors: mct/npt - updated : 09-11-2018

HGNC name	cyclin E1
HGNC id	1589

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001238 12 - 2021 NP_001229 - 410 - 2014 24947816 G1/S-specific cyclin-E1 LMW isoform - - - isoform 3 - 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive male system testis     highly respiratory lung bronchi

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Respiratory epithelial 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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