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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
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
  • STAT5A regulates the secretion of autocrine proangiogenic factors
  • 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
  • STAT5A-mediated repression of mtDNA expression also positively correlated with STAT5A binding to DLAT, both a gate-keeping metabolic enzyme and a component of mtDNA nucleoid in mitochondrial matrix
  • 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