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FLASH GENE

Symbol

ETS1

contributors: mct - updated : 18-05-2015

HGNC name	v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
HGNC id	3488

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	128.80 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005238 8 - 5228 NP_005229 51 441 - 2009 19377509 also called ETS1 variant 2/isoform 2 NM_001162422 4 - 4594 NP_001155894 27 225 highly expressed in fetal lung, expressed in breast adenocarcinomas 2009 19377509 also called Ets-1 p27 variant 3/isoform 3 variant resulting from the alternative splicing of exons III to VI lacks the threonine-38 AA, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes acts both at a transcriptional and a subcellular localization variant 2 NM_001143820 10 - 5143 NP_001137292 - 485 - 2009 19377509 also called variant 1/isoform 1

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 Lymphoid/Immune lymph node       highly   thymus       moderately Nervous nerve       moderately Reproductive female system breast mammary gland   moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Lymphoid

cell lineage	ETS1 and FOXD3 are expressed concomitantly in the cranial neural crest
cell lines
fluid/secretion	moderately in blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal A domain involved in transactivation, a leucine-rich nuclear export signal (NES) located at the N terminus
	an helix turn helix domain
	a C terminus with an ETS DNA-binding domain, required, but not sufficient by itself, to block antibody-secreting cells (ASCs) formation
	a PNT domain

conjugated

PhosphoP , Other

mono polymer

complex

HOMOLOGY

interspecies	homolog to rattus Ets1 (98.9 pc)
	homolog to murine Ets1 (97.3 pc)

Homologene

FAMILY

ETS family of transcription factors

CATEGORY

transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
text	is translocated to the cytoplasm in response to calcium-induced signals and facilitates the release of NFAT from noncoding RNA repressor of NFAT complex, which traps NFAT in the cytoplasm

basic FUNCTION	being a transcription regulator involved in maintenance of the normal pool of resting T and B lineage cells
	play an important role in regulating immune cell proliferation and differentiation
	regulates the expression of genes encoding enzymes involved in the degradation of the extracellular matrix, such as MMP1, MMP3, MMP7, and MMP9
	playing an important role in heart development and should provide important insights into some of the most common forms of congenital heart disease
	is essential for connective tissue growth factor (CTGF/CCN2) induction by TGFB1 in osteoblasts
	critical role for ETS1 regulation during B cell activation and cell cycle entry
	is critical for the expression of IL2 in human T cells
	ETS1 and PRDM1 play opposite roles during plasma cell differentiation, with ETS1 suppressing but PRDM1 promoting the process
	nuclear exit of ETS1 during erythroid maturation was mediated by a leucine-rich nuclear export signal (NES) located at the N terminus of ETS1
	is specifically required for migration of RAS/ERK activated cells
	has dual roles in mediating epithelial-specific RAS/ERK transcriptional functions
	critical role for ETS1 in the induction of human villus cytotrophoblast cells (CTBs)differentiation

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	negative regulation of cell proliferation
	positive regulation of erythrocyte differentiation

PATHWAY

metabolism

signaling

a component	forming a ternary complex with PAX proteins
	sumoylated on Lys-15 and Lys-227, preferentially by SUMO2
	ubiquitinated

INTERACTION

DNA	binding to sequence-specific

RNA

small molecule

protein	PAX2, PAX3, PAX5 (amino subterminal domain) potentially important for cellular differentiation
	coregulating osteopontin with PEBP2 alpha
	cooperating with cFos and cJUN SP100 for transcriptional activation
	activating CDKN2A
	binding to DAXX
	interacting with UBE2I
	SP100 interacts with the ETS1 transcription factor, reduces ETS1-DNA binding and inhibits ETS1 transcriptional activity on the MMP1 and PLAU promoters
	interacting with ERBB2 and MMP1 (enhancing the ERBB2-induced expression of MMP1)
	TAL1 interacts with RUNX1 and ETS1, and these transcription factors are critically required for TAL1 binding to genes that modulate T-cell differentiation
	interaction of a C-terminal fragment of DAXX with an N-terminal fragment of the sumoylated ETS1 transcription factor mediated by SIM-C
	ETS1 is essential for connective tissue growth factor (CTGF/CCN2) induction by TGFB1 in osteoblasts
	ETS1 activates, by direct interaction, the catalytic activity of PARP1 and is then poly(ADP-ribosyl)ated in a DNA-independent manner
	cooperates with ESR1 to stimulate estradiol-dependent growth in breast cancer cells and tumors
	promotes the expression of IL2 by nuclear factor of activated T-cells (NFAT)-dependent mechanisms
	very likely directly suppresses the expression of PRDM1 in Th1 cells by binding to the EBS2 of the PRDM1 promoter
	critical role of direct ETS1•RUNX1 interaction in ETS1 activation
	ETS1, another Ets family member, and FLI1 drive transcription from the CCL5 promoter, although FLI1 transactivation was significantly stronger
	ETS1 phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts RFWD2 binding, thereby stabilizing ETS1
	ETS1 acts as a positive regulator for SLFN11 expression in breast cancer cells

cell & other

REGULATION

Other

ID1 inhibits CDKN2A activation by ETS1 (and ETS2)

ASSOCIATED DISORDERS

corresponding disease(s)

HLHS2 , DEL11QD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion translocation     translocated t(11;19) (q23;p13) in ALL, fused with EWSR1 tumoral     --over   in both primary breast cancers and breast cancer cell lines, in progression and with metastasis tumoral     --other   deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Susceptibility

systemic lupus erythematous

Variant & Polymorphism SNP	3' UTR polymorphism associated with systemic erythematous (SLE), allele 1 with discoid lesions, allele 7 with vasculitis

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast target in breast cancer therapy, in cooperation with ERBB2 and MMP1

ANIMAL & CELL MODELS

	homozygous Ets1 deletion mice had large membranous ventricular septal defects, abnormal-appearing left ventricular morphology, characterized by a bifid cardiac apex, and non-apex-forming left ventricle
	Ets1-deficient mice develop a lupus-like disease characterized by high titers of immunoglobulin M (IgM) and IgG autoantibodies and immune-complex deposition in the kidneys