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FLASH GENE
Symbol FOSL1 contributors: mct/npt/shn - updated : 04-12-2012
HGNC name FOS-like antigen 1
HGNC id 13718
Location 11q13.1      Physical location : 65.659.691 - 65.667.997
Synonym name
  • FOS antigen-like 1
  • FOS-like antigen-1
  • fos-related antigen 1
  • Synonym symbol(s) FOSR1, FRA1, fra-1, FRA
    DNA
    TYPE functioning gene
    STRUCTURE 8.31 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • two critical elements of promoter, the upstream TPA response element (TRE) and the serum response element (SRE), are necessary for its induction in response to phorbol esters in pulmonary epithelial cell lines (Adiseshaiah 2008 )
  • MAPPING cloned Y linked N status confirmed
    Map cen - D11S4205 - D11S1883 - FOSL1 - D11S1889 - D11S4155 - qter
    Physical map
    SCYL1 11q11-q12 SCY1-like 1 (S. cerevisiae) LTBP3 11q12 latent transforming growth factor beta binding protein 3 MTVR1 11q23 Mouse Mammary Turmor Virus Receptor homolog 1 SSSCA1 11q13.1 Sjogren's syndrome/scleroderma autoantigen 1 DKFZp762C186 11q13.1 tangerin KCNK7 11q13 potassium channel, subfamily K, member 7 MAP3K11 11q13.3 mitogen-activated protein kinase kinase kinase 11 RELA 11q13 v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) SIPA1 11q13.3 signal-induced proliferation-associated gene 1 LOC387782 11 LOC387782 HTATIP 11q13 HIV-1 Tat interactive protein, 60kDa AYP1 11q13.1 AYP1 protein LOC390211 11 similar to Keratin, type II cytoskeletal 8 (Cytokeratin 8) (K8) (CK 8) LOC91056 11q13.1 hypothetical protein BC004895 OVOL1 11q13 ovo-like 1(Drosophila) FLJ30934 11q13.1 hypothetical protein FLJ30934 CFL1 11q13 cofilin 1 (non-muscle) MUS81 11q13 MUS81 endonuclease homolog (yeast) EFEMP2 11q13 EGF-containing fibulin-like extracellular matrix protein 2 CTSW 11q13.1 cathepsin W (lymphopain) FIBP 11q13.1 fibroblast growth factor (acidic) intracellular binding protein DIPA 11q12.1 hepatitis delta antigen-interacting protein A FOSL1 11q13 FOS-like antigen 1 P5326 11q13.1 hypothetical protein p5326 DRAP1 11q13.3 DR1-associated protein 1 (negative cofactor 2 alpha) FLJ32880 11q13.1 hypothetical protein FLJ32880 SART1 11q12-q13 squamous cell carcinoma antigen recognised by T cells MGC11102 11q13.1 hypothetical protein MGC11102 BANF1 11q13.1 barrier to autointegration factor 1 CST6 11q13.2 cystatin E/M CATSPER1 11q12.1 cation channel, sperm associated 1 GAL3ST2 11q13 cation channel, sperm associated 1 SF3B2 11cen-q23 splicing factor 3b, subunit 2, 145kDa PACS1 11q13.1 phosphofurin acidic cluster sorting protein 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1668 - 271 - Adiseshaiah (2008)
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Endocrinepancreas   predominantly
    Lymphoid/Immunelymph node    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialsecretoryglandularendocrinepredominantly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoclast
    cell lineage
    cell lines High Fra-1 levels are associated with enhanced tumour cell proliferation, survival, migration and invasion
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one bzip domain
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Fosl1, Mus musculus
    ortholog to Fosl1, Rattus norvegicus
    ortholog to FOSL1, Pan troglodytes
    ortholog to fosl1a, Danio rerio
    Homologene
    FAMILY
  • FOS family of transcription factors
  • Activator Protein-1 (AP-1) transcription factor superfamily
  • CATEGORY regulatory , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus
    basic FUNCTION
  • involved in the cell proliferation, differentiation, and transformation
  • may likely play an important role in the maintenance/progression of malignant gliomas
  • in regulating bone mass through bone matrix production by osteoblasts and chondrocytes
  • inhibits inducible IL-8 transcription
  • like FOS, belongs to a small group of proteins that may, under certain circumstances, undergo ubiquitin-independent degradation by the proteasome (Basbous 2007)
  • functions as a positive transcriptional regulator in human keratinocytes
  • key regulator of cell motility, invasiveness, growth and survival of tumor cells
  • might play a role in the progression and prognosis of non-small-cell lung cancer
  • modulates JUN dimer composition by promoting the accumulation of c-Jun in response to oncogenic RAS signaling
  • key downstream effector of the PI3K/AKT signaling pathway responsible for development of trophoblast lineages integral to establishing the maternal-fetal interface
  • constitutes a regulatory module with microRNA-138 that may play an important role in cancer initiation and progression
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , immunity/defense , carcinogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • forming heterodimers, the AP-1 complex with proteins of the JUN family
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • USF
  • histone deacetylase-1
  • TXLNG regulate later osteoblast function through inhibition of FOSL1
  • posttranslational regulator of c-Jun stability in RAS transformation
  • occupy regions of the MMP9 promoter in trophoblast cells critical for the regulation of MMP9 gene expression
  • cell & other
    REGULATION
    activated by Human T-cell leukemia virus type 1 Tax
    induced by TNFSF11(RANKL)
    Other transcriptional target of C.Fos during osteoclast differentiation
    TBP-1 and 19S proteasomal subunit
    down-regulated by microRNA-138
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer in progression
    tumoral     --over  
    in pancreatic cancer
    tumoral     --low  
    in non-small-cell lung cancer with poor survival (Ma 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • target for therapeutic interventions in malignant gliomas
  • gene ablation can suppress the invasive phenotypes of many tumor cell lines
  • potentially useful in pancreatic tumor targeting or as tumor markers
  • lethality of fra-1-knockout mice can be rescued by specific deletion of Fra-1 only in the mouse embryo
  • autoregulatory loop between JUN and FOSL1 might represent an important determinant for the increased JUN activity and a novel target for therapeutic intervention in tumorigenesis
  • ANIMAL & CELL MODELS
  • Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis
  • fra-1-knockout mice die in utero likely due to placental defects
  • Mice lacking Fra-1 (fra-1(delta/delta)) are viable and develop osteopenia, a low bone mass disease