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FLASH GENE

Symbol

E2F3

contributors: mct/pgu - updated : 05-04-2016

HGNC name	E2F transcription factor 3
HGNC id	3115

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	91.81 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001949 7 - 5050 NP_001940 - 465 - 2009 19136625 e2F3a variant 2 - - - isoform 2 - - - 2009 19136625 also called E2F3b required for myogenic differentiation, not depending on RB1

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 Digestive intestine large intestine colon   highly Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a DNA binding domain
	a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins
	putative leucine zippers
	a carboxyterminal domain of interaction with pRB

HOMOLOGY

Homologene

FAMILY

E2F/DP family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	controlling genes regulating S phase entry and DNA synthesis
	involved in transcription repression in quiescent cell by interaction with histone deacetylase
	playing a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses
	could exert a strong influence over the susceptibility to oncogenic transformation
	regulate cell cycle-dependent gene expression through opposing transcriptional activating and repressing activities in growing and quiescent cells
	have a critical role in modifying cellular proliferation rate in bladder and prostate cancer
	mediator of DNA damage-induced apoptosis
	induces apoptosis in Hepatocellular carcinoma cells and plays important roles in regulating transcription
	E2F3 is an oncogene with strong proliferative potential and is regularly dysregulated or overexpressed in cancer
	in contrast to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial protective role in neuronal death evoked by DNA damage, hypoxia, and global ischemic insult

CELLULAR PROCESS	cell cycle
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	binds specifically to RB1 protein, in a cell-cycle dependent manner
	p107 (RBL1), p130 (RBL2) binding
	modulates Aurora-A mRNA expression during the cell cycle (directly binds to Aurora-A promoter and stimulates the promoter activity)
	with E2F1 contribute to ATM-dependent phosphorylation of TP53 and apoptosis in cells expressing E1A
	HELLS interacts with E2F3A and cooperates with its oncogenic functions
	PUM1 and PUM2 repress the translation of E2F3 by binding to the E2F3 3prime untranslated region (UTR) and also enhance the activity of multiple E2F3 targeting microRNAs
	TRIM28 has anti-proliferative activity in lung cancers via repression of E2F3, E2F4 that are critical for cell proliferation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in retinoblastoma tumoral     --over   and amplified in invasively growing bladder cancer tumoral     --over   inactivation of the RB1 pathway is required in addition to E2F3 overexpression in bladder tumours tumoral     --over   in liver cancer tissues tumoral     --over   of KIF14 and E2F3 protein in retinoblastoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     E2F3-Aurora-A axis could be an important target for cancer intervention

ANIMAL & CELL MODELS