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FLASH GENE
Symbol STAT5A contributors: mct/npt - updated : 17-12-2016
HGNC name signal transducer and activator of transcription 5A
HGNC id 11366
Location 17q21.2      Physical location : 40.439.564 - 40.463.958
Synonym name mammary gland factor
Synonym symbol(s) MGF, STAT
DNA
TYPE functioning gene
STRUCTURE 24.40 kb     20 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence cytosine-phosphate-guanine/HTF
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 4314 - 794 - 2001 11413148
19 - 2414 - 794 - 2001 11413148
18 - 4132 - 763 - 2001 11413148
18 - 4135 - 764 - 2001 11413148
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   highly
 tonsils   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Lymphoid    
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunelymphocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminus conserved domain
  • the coiled coil domain
  • the DNA binding domain
  • a linker region
  • a SRC homology domain 2 (SH2)
  • a critical site of tyrosine phosphorylation and the carboxy-terminal transactivation domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    intraspecies homolog to STAT5B
    Homologene
    FAMILY
  • STAT family of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • translocated to nucleus after dimerization
  • after tyrosine phosphorylation, STAT5A accumulates in the nucleus because of its retention by DNA binding (Iyer 2008)
  • basic FUNCTION
  • signal transducer and activator of transcription of the GH/PRL JAK/STAT pathway
  • molecular regulator of proliferation, differentiation, and apoptosis in lymphohematopoietic cells (Mahajan 2001)
  • playing a critical role for many, but not all, aspects of steady state lymphoid lineage development and maintenance
  • required for thymopoiesis in a development stage-specific manner
  • can induce a TP53- and Rb-dependent cellular senescence response (Mallette 2007)
  • critical transcription factor for a number of physiological processes including hematopoiesis and mammary gland development (Iyer 2008)
  • signal transducer and activator of transcription 5A and 5B (STAT5A/B) is critical for the viability of prostate cancer cells (Tan 2008)
  • STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes (Kimura 2009)
  • plays a pivotal role in the proliferation, secretory differentiation, and survival of mammary epithelial cells
  • critically regulates human dendritic cells (DC) development, with specific requirements for the level of STAT5A activation at distinct differentiation stages
  • negatively regulates T follicular helper (Tfh) cell generation and function (pMID: 22318729)
  • critical role of STAT5A, STAT5B transcription factor tetramerization for cytokine responses and normal immune function
  • its activation may modulate the differentiation of T helper cells through attenuation of TGFB1 stability and production
  • unphosphorylated STAT5A functions as a tumor suppressor capable of repressing multiple oncogenes via heterochromatin formation
  • STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans
  • is an early step in establishing transcription complexes on genes specifically expressed in mammary epithelium
  • plays an important role in ABCG2 expression during lactation
  • STAT5A activates distal-less homeobox 5 (DLX5) in human bone marrow-derived stromal cells (hBMSCs) and enhances osteogenesis
  • STAT5A inhibition enhances bone formation by promoting osteogenesis of BMSCs
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • JAK/STAT
  • STAT5A/PRL/VEGFA signaling cascade in human brain endothelial cells (EC)
  • a component
  • homodimerizing or heterodimerizing with STAT5B
  • INTERACTION
    DNA binding to target genes
    RNA
    small molecule
    protein
  • can serve as a functional substrate of Bruton's tyrosine kinase (BTK)(BTK plays a nonredundant and pivotal role in B cell antigen receptor-mediated STAT5A activation in B cells) (Mahajan 2001)
  • binds to consensus sequences within the AKT1 locus in a growth factor-dependent manner to initiate transcription of a unique AKT1 mRNA from a distinct promoter, which is only active in the mammary gland (pMID: 20385773)
  • HIF2A is an important STAT5A target gene in human hematopoietic stem cells
  • functional interaction between FYN, AGAP2, and STAT5A in mediating adipogenesis
  • CBL interacts with the transcription factor STAT5A, and STAT5A forms a complex with RUNX2, a master transcription factor controlling osteoblastogenesis
  • SIRT1 negatively regulates GH-induced STAT5A, STAT5B phosphorylation and IGF1 production via deacetylation of STAT5A, STAT5B in the liver
  • TNFSF11 is a direct PGR target gene and STAT5A has a novel role as a cofactor in PGR-mediated transcriptional signaling in the mammary gland
  • FOSL2 is a novel STAT5A target gene, regulated by IL2 in activated CD4 T cells
  • NAA10 inhibits the metastasis of breast cancer cells by targeting STAT5A
  • CD82 regulated BCL2L12 expression via STAT5A and AKT1 signaling and stimulated proliferation and engrafting of leukemia cells
  • cell & other
  • T cell receptor and stimulating T cell proliferation
  • REGULATION
    activated by growth hormone, prolactin, erythropoietin, and interleukin-2, which stimulate the activation of STAT5A by tyrosine phosphorylation (Iyer 2008)
    a variety of hormones and cytokines including interleukin 2
    induced by IL6, that also induces STAT5A activation in both CD4 and CD8 T as well as NK cells
    repressed by NCOR2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in myelo- and lymphoproliferative disease induced by TEL/JAK2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS