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FLASH GENE
Symbol FLI1 contributors: mct - updated : 18-05-2017
HGNC name Friend leukemia virus integration 1
HGNC id 3749
DNA
TYPE virus associated
STRUCTURE 126.73 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • promoter is upregulated by Ets factors ETS1, ETS2, ELF1 either alone or in combination with GATA factors, but is inhibited by TEL
    • MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type untranslated
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 3993 - 452 - 2008 18174230
    7 - 3442 - 259 - 2008 18174230
    10 - 4049 - 419 - 2008 18174230
    10 - 4166 - 386 - 2008 18174230
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, growth/childhood
    Text widely, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an ETS (erythroblast transformation specific) DNA-binding domain
  • a SAM pointed domain (sterile alpha motif)
  • a helix-loop-helix (HLH) domain
  • a fusion of a leucine rich repeat (LRR) domain with a gelsolin-like domain
  • C-terminal transcriptional activation domain of FLI1 negatively modulates mononuclear phagocyte development
    • HOMOLOGY
    Homologene
    FAMILY
  • erythroblast transformation specific (ETS) family
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • sequence-specific transcriptional activator
  • required with GATA1 for development of megakaryocytes
  • first nuclear marker of endothelial differentiation
  • contributes to the malignancy of breast cancer by inhibiting apoptosis through upregulated expression of the BCL2 gene
  • plays an important role in the mononuclear phagocyte development
  • novel function for FLI1 in T cell development and leukaemogenesis
  • played an essential role in the development and progression of ovarian cancers
  • is a novel regulator of the proinflammatory chemokine CCL2, that interacts with other transcription factors to form a complex transcriptional mechanism for the activation of CCL2 and mediation of the inflammatory response
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text histogenesis, embryogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RAS binding protein
  • regulating TGFBR2 expression
  • is a substrate of SGK3 that functions downstream of PI 3-kinase (SGK3 can associate with FLII and phosphorylate FLII at residues Ser(436) and Thr(818))
  • binding partner of NXN
  • interaction with ACTL6A (FLI1 can bind directly to both ESR1 and ACTL6A, an actin-related component of the SWI/SNF complex, suggesting that FLI1 may recruit SWI/SNF to ESR1 target genes via interaction with ACTL6A)
  • binds directly to DAAM1 and DIAPH1 (FLI1 enhances the intrinsic actin assembly activity of DAAM1 and DIAPH1 and is required for DAAM1-induced actin assembly in living cells)
  • suppression of FOXO1 function by EWSR1-FLI1 fusion protein may contribute to cellular transformation in Ewing's family tumors
  • role of FLI1 as a negative regulator of the ESR1 gene in dermal fibroblasts
  • FLI1, ELF1, and GABPA regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors
  • FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer
  • FLI1 drives transcription from the CCL5 promoter in a dose-dependent manner
  • ETS1, another Ets family member, and FLI1 drive transcription from the CCL5 promoter, although FLI1 transactivation was significantly stronger
  • FLI1 gene actively promotes transcription from the CCL2 gene promoter in a dose-dependent manner
  • Ca2+ influx through the TRPV4 channel regulates FLII-MYH9 interaction, which in turn enables generation of the cell extensions essential for collagen remodeling
  • FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) TCDM , DEL11QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in acute myeloid leukemia
    constitutional     --low  
    by heavy methylation of the CpG islands in the promoter region was demonstrated in SSc scleroderma (systemic sclerosis) fibroblasts and skin biopsy specimens (epigenetic mechanisms may mediate the fibrotic manifestations of SSc)
    tumoral fusion      
    with EWSR1, t(11;22)(q24;q12) in Ewing sarcoma, cancer-specific molecule that binds to RHA essential for the function of EWS-FLI1 (Erkizan 2009)
    tumoral     --low  
    in in metastatic melanoma (Torlakovic 2008)
    tumoral fusion      
    fusion of SLC45A3 exon 1 with FLI1 exon 3 in prostate cancer
    tumoral     --other  
    deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma
    constitutional     --over  
    in 5q- syndrome protects megakaryocytic cells from ribosomal stress contrary to erythroid cells and contributes to effective though dysplastic megakaryopoiesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential prognostic marker in ovarian cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    Small molecules that disable EWS-FLI1 function with minimal toxicity, in particular sparing hematopoetic stem cells, could potentially provide a valuable adjuvant therapy for patients with Ewing sarcoma family tumors
    cancerreproductiveovary
    potential prognostic marker and therapeutic molecular target in ovarian cancer
    ANIMAL & CELL MODELS
    hemorrhage impaired hematopoiesis and lethality in mouse embryo with a targetted disruption of Fli1