STAT6

STAT6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1OJ5, 4Y5W, 4Y5U
Identifiers
Aliases	STAT6, D12S1644, IL-4-STAT, STAT6B, STAT6C, signal transducer and activator of transcription 6
External IDs	OMIM: 601512; MGI: 103034; HomoloGene: 2373; GeneCards: STAT6; OMA:STAT6 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.3 Start 57,095,408 bp[1] End 57,132,139 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 D3|10 74.59 cM Start 127,478,855 bp[2] End 127,496,826 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte right ovary left ovary canal of the cervix spleen gastric mucosa right adrenal cortex right uterine tube left uterine tube body of uterus Top expressed in granulocyte lumbar spinal ganglion mesenteric lymph nodes ascending aorta aortic valve thymus spleen lip stroma of bone marrow esophagus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function identical protein binding sequence-specific DNA binding protein phosphatase binding DNA binding protein binding DNA-binding transcription factor activity RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleoplasm membrane raft cytoplasm cytosol nuclear membrane Biological process regulation of transcription by RNA polymerase II T-helper 1 cell lineage commitment regulation of cell population proliferation response to cytokine interleukin-4-mediated signaling pathway regulation of transcription, DNA-templated cellular response to hydrogen peroxide mammary gland epithelial cell proliferation cellular response to reactive nitrogen species positive regulation of type I interferon production positive regulation of isotype switching to IgE isotypes mammary gland morphogenesis negative regulation of type 2 immune response negative regulation of transcription by RNA polymerase II signal transduction transcription, DNA-templated positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II cytokine-mediated signaling pathway positive regulation of cold-induced thermogenesis defense response receptor signaling pathway via JAK-STAT response to peptide hormone growth hormone receptor signaling pathway via JAK-STAT Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6778 20852 Ensembl ENSG00000166888 ENSMUSG00000002147 UniProt P42226 P52633 RefSeq (mRNA) NM_001178078 NM_001178079 NM_001178080 NM_001178081 NM_003153 NM_009284 RefSeq (protein) NP_001171549 NP_001171550 NP_001171551 NP_001171552 NP_003144 NP_033310 Location (UCSC) Chr 12: 57.1 – 57.13 Mb Chr 10: 127.48 – 127.5 Mb PubMed search [3] [4]
Wikidata
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Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins.^[5] The proteins of STAT family transmit signals from a receptor complex to the nucleus and activate gene expression. Similarly as other STAT family proteins, STAT6 is also activated by growth factors and cytokines. STAT6 is mainly activated by cytokines interleukin-4 and interleukin-13.^[5]

In the human genome, STAT6 protein is encoded by the STAT6 gene, located on the chromosome 12q13.3-q14.1.^[6] The gene encompasses over 19 kb and consists of 23 exons.^[7] STAT6 shares structural similarity with the other STAT proteins and is composed of the N-terminal domain, DNA binding domain, SH3- like domain, SH2 domain and transactivation domain (TAD).^[7]

STAT proteins are activated by the Janus family (JAKs) tyrosine kinases in response to cytokine exposure.^[8] STAT6 is activated by cytokines interleukin-4 (IL-4), and interleukin-13 (IL-13) with their receptors that both contain the α subunit of the IL-4 receptor (IL-4Rα).^[8] Tyrosine phosporylation of STAT6 after stimulation by IL-4 results in the formation of STAT6 homodimers that bind specific DNA elements via a DNA-binding domain.^[5][9]

STAT6-mediated signaling pathway is required for the development of T-helper type 2 (Th2) cells and Th2 immune response.^[8] Expression of Th2 cytokines, including IL-4, IL-13, and IL-5, was reduced in STAT6-deficient mice.^[5] STAT 6 protein is crucial in IL4 mediated biological responses. It was found that STAT6 induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. IL-4 stimulates the phosphorylation of IL-4 receptor, which recruits cytosolic STAT6 by its SH2 domain and STAT6 is phosphorylated on tyrosine 641 (Y641) by JAK1, which results in the dimerization and nuclear translocation of STAT6 to activate target genes.^[10] Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2), expression of cell surface markers, and class switch of immunoglobulins.^[11]

Activation of STAT6 signaling pathway is necessary in macrophage function, and is required for the M2 subtype activation of macrophages.^[12][13][14] STAT6 protein also regulates other transcription factor as Gata3, which is important regulator of Th2 differentiation.^[5] STAT6 is also required for the development of IL-9-secreting T cells.^[5]

STAT6 also plays a critical role in Th2 lung inflammatory responses including clearance of parasitic infections and in the pathogenesis of asthma.^[8] Th2-cell derived cytokines as IL-4 and IL-13 induce the production of IgE which is  a major mediator in allergic response.^[9] Association studies searching for relation of polymorphisms in STAT6 with IgE level or asthma discovered a few polymorphisms significantly associated with examined traits. Only two polymorphisms showed repeatedly significant clinical association and/or functional effect on STAT6 function (GT repeats in exon 1 and rs324011 polymorphism in intron 2).^[7]

STAT6 has been shown to interact with:

• CREB-binding protein,^[15][16]
• EP300,^[15]
• IRF4,^[17]
• NFKB1,^[18]
• Nuclear receptor coactivator 1,^[16][19] and
• SND1.^[20]

• Gene fusion
  • Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors.^[21]
• Amplification
  • STAT6 is amplified in a subset of dedifferentiated liposarcoma.^[22]

• Interleukin 4

• STAT6+Transcription+Factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)