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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
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
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 5228 51 441 - 2009 19377509
also called ETS1 variant 2/isoform 2
4 - 4594 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
  • 10 - 5143 - 485 - 2009 19377509
    also called variant 1/isoform 1
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     thymus   moderately
    Nervousnerve   moderately
    Reproductivefemale systembreastmammary gland moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    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