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FLASH GENE
Symbol SPI1 contributors: mct - updated : 24-10-2017
HGNC name spleen focus forming virus (SFFV) proviral integration oncogene spi1
HGNC id 11241
Location 11p11.2      Physical location : 47.376.408 - 47.400.127
Synonym name
  • hematopoietic lineage-specific transcription factor PU.1
  • SPI-1 proto-oncogene
  • 31 kDa transforming protein
  • hematopoietic transcription factor PU.1
  • Synonym symbol(s) OF, PU.1, SFPI1, SPI-1, SPI-A
    DNA
    TYPE functioning gene
    STRUCTURE 23.72 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1426 - 271 - 2008 18288635
    5 - 1423 31.1 270 - 2008 18288635
    EXPRESSION
    Type widely
    constitutive of
       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
     tonsils   highly
    Urinarykidneynephronrenal capsuleglomerulus 
    cell lineage
    cell lines various hematopoietic cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • ETS (erythroblast transformation specific) DNA-binding domain at the C terminus, activating gene expression during myeloid and B-lymphoid cell development
  • HOMOLOGY
    intraspecies homolog to Pu-1
    Homologene
    FAMILY
  • SPI-group ETS-protein transcription factors family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • required for the development of both myeloid and lymphoid lineages (role indispensable)
  • can also regulate alternative splicing of target genes
  • repressing GATA1 function during myelopoiesis
  • with PLAGL1, and MED15 cooperate to enhance NCF2 promoter-reporter activity
  • as specific transcription factors SPIB, and SPIC, regulate follicular B cell differentiation
  • is a major transcriptional activator of LIMD1
  • is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors
  • SPI1 and SPIB are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage
  • ETV5 and SPI1 function in parallel to promote Th9 cell development
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding and associating with NCF4 for phox expression and granulocytic differentiation
  • regulating expression of crucial myeloid genes such as CSF1, CSF2, CSF3
  • interazcting with GATA1 (Ets domain of SPI1 and the GATA1 C-terminal zinc finger (CF) form a low affinity interaction in which specific regions of each protein are implicated)
  • interacting with NFATC1 (SPI1 confers specificity to the NFATC1 response to macrophage lineage cells)
  • interacting with TRIM33 (regulation of adult hematopoiesis through TRIM33-mediated transcriptional repression of TAL1 and SPI1 target genes)
  • SPI1 is a critical factor for the expression of CD80 and CD86
  • RUNX1 cooperates with SPI1 to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR)
  • MT1A is a direct target gene negatively regulated by SPI1
  • SPI1 and GATA1 transactivate FCER1A
  • is a critical regulator of CITED2, as SPI1 repressed CITED2 expression in a DNMT3A/B-dependent manner in normal CD34+ cells
  • TCF3 antagonism of SPI1 activity contributes likely to its ability to commit multipotential hematopoietic progenitors to the lymphoid lineages
  • critical role of SPI1 in the regulation of TLR1, 2, 4 and of CD14
  • mechanistically, METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and MYC) through N6-methyladenosine (m6A)modification, while the protein itself is negatively regulated by SPI1
  • cell & other
    REGULATION
    repressed by GATA1, during erythropoiesis
    Other repressing MMP2 transcription in mesengial cells
    inactivated by CEBPA
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in acute myeloid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    is a potential target for the treatment of immune-related diseases
    ANIMAL & CELL MODELS
  • mice deficient in both Spib and Spi1 in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation, and developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age