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FLASH GENE
Symbol STAT6 contributors: mct - updated : 26-01-2015
HGNC name signal transducer and activator of transcription 6, interleukin-4 induced
HGNC id 11368
Location 12q13.3      Physical location : 57.489.194 - 57.505.196
Synonym name
  • IL-4 Stat
  • interleukin-4 induced
  • transcription factor IL-4 STAT
  • Synonym symbol(s) D12S1644, IL4STAT, IL-4-STAT, STAT6B, STAT6C
    DNA
    TYPE functioning gene
    SPECIAL FEATURE
    text overlapping D12S1644
    STRUCTURE 15.97 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    regionally located tail to tail and a common termination region with NAB2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4031 94 847 - 1996
    - splicing 4050 94 847 - 1996
    N terminal truncated forms
    - splicing 3976 94 847 - 1996
    lacking ths SH2 domain
    - - 3755 81.6 737 - 1996
    - - 3894 81.6 737 - 1996
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    Urinarykidney     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    Urinaryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminus conserved domain
  • a coiled coil domain
  • a DNA binding domain,a linker region
  • a SRC homology domain 2 (SH2)
  • a critical site of tyrosine phosphorylation and the C-terminal transactivation domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans Y51h4a17
    Homologene
    FAMILY
  • transcription factor STAT family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    text translocated to the nucleus after activation
    basic FUNCTION
  • involved in signaling from the leptin receptor
  • critical regulator of transcription for interleukin-4 (IL4)-induced genes
  • survival factor in prostate cancer and regulates the genetic transcriptional program that is responsible for prostate cancer progression
  • recruits CREBBP and chromatin-modifying activities to the promoter
  • with its IL4-signalling pathway are critical for the expression of Th2 effector immune responses in peripheral tissues such as the skin, lung and gut
  • facilitator of the nuclear receptor PPARG-regulated gene expression in macrophages and dendritic cells
  • role for STAT6 in enhancing cell proliferation and invasion in Glioblastoma, which may explain why up-regulation of STAT6 correlates with shorter survival times in glioma patients
  • plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines
  • mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum
  • STAT6-STAT1 axis regulates osteoclast stimulatory transmembrane protein and dendritic cell-specific transmembrane protein expression and governs fusogenic mechanisms in foreign body giant cells
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • homodimerizing or heterodimerizing with another STAT protein
  • LITAF forms a complex with human STAT6, which translocates into the nucleus to upregulate cytokine transcription
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between STAT6 and CREBBP was found to be mediated through SND1
  • SPIC interacted specifically with the C-terminus of STAT6 (interaction between SPIC and STAT6 is the basis for a novel mechanism for regulation of IL4 induced gene expression)
  • phosphorylated STAT6 may serve as a cytoplasmic substrate for PTPN1 (interacted with STAT6 in an interleukin 4 (IL4)-inducible manner, and negative regulator of interleukin 4-induced STAT6 signaling)
  • binds the ACP5 promoter after IL4 treatment and directly enhances its expression)
  • STAT6 and JUN proteins were found to physically cooperate with each other and upregulated IL24 gene transcription
  • PKD1 cytoplasmic tail associates with the transcription factors TPX2 and STAT6
  • IL4-activated STAT6 is required for repressing the expression of T-bet and FOXP3 in Th9 cells, transcription factors that inhibit IL9 production, and STAT6 is required for the induction of IRF4, which promotes Th9 development
  • TYK2 controls STAT1 and STAT6 activation in response to IL13 stimulation
  • the gene fusion can convert a transcriptional repressor (NAB2) into a transcriptional activator (NAB2-STAT6) of mitogenic pathways that can be subverted during neoplastic progression
  • while IL4 inhibits and activates different sets of lysosomal genes, STAT6 mediates only the activating effects of IL4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL4
  • IL4 increases the binding of STAT6 to its response elements in the IL19 promoter
  • CBLB suppresses ORMDL3 expression through STAT6
  • TMEM173 promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6)
  • cell & other
    REGULATION
    activated by specifically by IL4 and IL13RA1 jointly
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in primary mediastinal B-cell lymphoma
    tumoral     --over  
    in the fibromuscular stroma of prostate cancer
    constitutional       gain of function
    in renal cysts and is part of a positive feedback loop involving IL13 and its receptor
    tumoral fusion      
    NAB2/STAT6, in solitary fibrous tumor (SFT)/hemangiopericytoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    tumorkidneypolycystic kidney
    its pharmacological inhibition is a promising treatment of PKD
    cancerbrainglioma/neuroblstoma
    new and potentially promising therapeutic target
    ANIMAL & CELL MODELS
  • aberrantly activated in cyst-lining cells in PKD mouse models